<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02973087</url>
  </required_header>
  <id_info>
    <org_study_id>071301</org_study_id>
    <secondary_id>2016-001478-14</secondary_id>
    <nct_id>NCT02973087</nct_id>
  </id_info>
  <brief_title>rVWF IN PROPHYLAXIS</brief_title>
  <official_title>A PROSPECTIVE, PHASE 3, OPEN-LABEL, INTERNATIONAL MULTICENTER STUDY ON EFFICACY AND SAFETY OF PROPHYLAXIS WITH rVWF IN SEVERE VON WILLEBRAND DISEASE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Baxalta Innovations GmbH, now part of Shire</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this phase 3 study is to investigate the efficacy and safety, including&#xD;
      immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics&#xD;
      (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment&#xD;
      with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with&#xD;
      severe von Willebrand disease (VWD).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2017</start_date>
  <completion_date type="Actual">July 6, 2020</completion_date>
  <primary_completion_date type="Actual">July 6, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12</measure>
    <time_frame>Baseline through Month 12</time_frame>
    <description>The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (&gt;) 0 through 2,&gt;2 through 5,&gt;5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram [kg]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs</measure>
    <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Based on Severity of TEAEs</measure>
    <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With TEAEs Based Causality</measure>
    <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Thromboembolic Events</measure>
    <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
    <description>Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Hypersensitivity Reactions</measure>
    <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
    <description>Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)</measure>
    <time_frame>Baseline through Month 12</time_frame>
    <description>Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)</measure>
    <time_frame>Baseline through Month 12</time_frame>
    <description>The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin</measure>
    <time_frame>Baseline through Month 12</time_frame>
    <description>Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</measure>
    <time_frame>Baseline up to end of study (approximately 32 months)</time_frame>
    <description>Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters</measure>
    <time_frame>Baseline up to end of study (approximately 32 months)</time_frame>
    <description>Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram ([IU/dL]/[IU/kg]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>IR based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units*hour per deciliter (IU*h/dL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax based on VWF:Rco activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Factor VIII (FVIII) Clotting Activity</measure>
    <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
    <description>FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Von Willebrand Disease</condition>
  <arm_group>
    <arm_group_label>All Study Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive prophylaxis with rVWF in two cohorts: on-demand (OD) cohort (previously treated with OD) and pdVWF switch cohort (participants switching from prophylactic treatment with pdVWF).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>von Willebrand factor (Recombinant)</intervention_name>
    <description>OD participants will receive intravenous (IV) rVWF:RCo at an initial prophylactic dose of 50 +/- 10 International Unit per Kilogram (IU/kg) twice (two infusions) a week for at least 12 months up to 15 months and may be increased up to 80 IU/kg. pdVWF switch cohort participants will receive rVWF:RCo equivalent (± 10%) to the weekly VWF dose received during prophylactic treatment with pdVWF.</description>
    <arm_group_label>All Study Participants</arm_group_label>
    <other_name>BAX 111</other_name>
    <other_name>rVWF</other_name>
    <other_name>VONVENDI</other_name>
    <other_name>vonicog alfa</other_name>
    <other_name>BAX111</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Antihemophilic Factor (Recombinant)</intervention_name>
    <description>During prophylaxis period any bleeding episodes requiring substitution therapy with VWF concentrate to control bleeding will be treated with rVWF with or without ADVATE. Participants will receive rFVIII IV if necessary for OD treatment of breakthrough bleeds or for peri-operative. The dose will be according to the bleeding type and severity and it will be adjusted to the clinical response.</description>
    <arm_group_label>All Study Participants</arm_group_label>
    <other_name>ADVATE</other_name>
    <other_name>Recombinant Factor VIII</other_name>
    <other_name>rFVIII</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant has a documented diagnosis of severe von Willebrand disease (VWD)&#xD;
             (baseline Von Willebrand factor: Ristocetin cofactor activity (VWF:RCo) less than (&lt;)&#xD;
             20 International Units/Deciliter [IU/dL]) with a history of requiring substitution&#xD;
             therapy with von Willebrand factor concentrate to control bleeding&#xD;
&#xD;
               1. Type 1 (VWF:RCo &lt;20 IU/dL) or,&#xD;
&#xD;
               2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype),&#xD;
                  Type 2M or,&#xD;
&#xD;
               3. Type 3 (Von Willebrand factor antigen (VWF:Ag) less than or equal to [&lt; or =] 3&#xD;
                  IU/dL).&#xD;
&#xD;
          2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient&#xD;
             history or at screening.&#xD;
&#xD;
          3. For on-demand patient group, participant currently receiving on-demand treatment for&#xD;
             whom prophylactic treatment is recommended by the investigator.&#xD;
&#xD;
          4. For Plasma derived von Willebrand factor (pdVWF) product switch patient group,&#xD;
             participant has been receiving prophylactic treatment of pdVWF products for no less&#xD;
             than 12 months prior to screening.&#xD;
&#xD;
          5. For on-demand patient group, participant has greater than or equal to (&gt;or=) 3&#xD;
             documented spontaneous bleeds (not including menorrhagia) requiring von Willebrand&#xD;
             factor (VWF) treatment during the past 12 months.&#xD;
&#xD;
          6. Availability of records to reliably evaluate type, frequency and treatment of bleeding&#xD;
             episodes during at least 12 months preceding enrollment. Up to 24 months retrospective&#xD;
             data should be collected if available. Availability of dosing and factor consumption&#xD;
             during 12 months (up to 24 months) of treatment prior to enrollment is required for&#xD;
             pdVWF switch participants and is desired (but not a requirement) for on-demand&#xD;
             participants.&#xD;
&#xD;
          7. Participant is &gt; or = 18 years old at the time of screening and has a body mass index&#xD;
             &gt; or = 15 but &lt;40 kilogram per meter square (kg/m^2).&#xD;
&#xD;
          8. If female of childbearing potential, participant presents with a negative blood/urine&#xD;
             pregnancy test at screening and agrees to employ adequate birth control measures for&#xD;
             the duration of the study.&#xD;
&#xD;
          9. Participant is willing and able to comply with the requirements of the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The participant has been diagnosed with Type 2N Von Willebrand disease (VWD), pseudo&#xD;
             VWD, or another hereditary or acquired coagulation disorder other than VWD (eg&#xD;
             qualitative and quantitative platelet disorders or prothrombin time [PT]/international&#xD;
             normalized ratio [INR] greater than [&gt;]1.4).&#xD;
&#xD;
          2. The participant is currently receiving prophylactic treatment with more than 5&#xD;
             infusions per week.&#xD;
&#xD;
          3. The participant is currently receiving prophylactic treatment with a weekly dose&#xD;
             exceeding 240 IU/kg.&#xD;
&#xD;
          4. The participant has a history or presence of a VWF inhibitor at screening.&#xD;
&#xD;
          5. The participant has a history or presence of a Factor VIII (FVIII) inhibitor with a&#xD;
             titer ≥0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or &gt; or = 0.6&#xD;
             Bethesda Unit (BU) (by Bethesda assay).&#xD;
&#xD;
          6. The participant has a known hypersensitivity to any of the components of the study&#xD;
             drugs, such as to mouse or hamster proteins.&#xD;
&#xD;
          7. The participant has a medical history of immunological disorders, excluding seasonal&#xD;
             allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.&#xD;
&#xD;
          8. The participant has a medical history of a thromboembolic event.&#xD;
&#xD;
          9. The participant is human immunodeficiency virus (HIV) positive with an absolute Helper&#xD;
             T cell (CD4) count &lt;200/ cubic millimeter (mm^3).&#xD;
&#xD;
         10. The participant has been diagnosed with significant liver disease per investigator's&#xD;
             medical assessment of the participant's current condition or medical history or as&#xD;
             evidenced by any of the following: serum alanine aminotransferase (ALT) greater than 5&#xD;
             times the upper limit of normal; hypoalbuminemia; portal vein hypertension (e.g.,&#xD;
             presence of otherwise unexplained splenomegaly, history of esophageal varices).&#xD;
&#xD;
         11. The participant has been diagnosed with renal disease, with a serum creatinine (CR)&#xD;
             level &gt; or = 2.5 milligram per deciliter (mg/dL).&#xD;
&#xD;
         12. The participant has a platelet count &lt;100,000/ milliliter (mL) at screening.&#xD;
&#xD;
         13. The participant has been treated with an immunomodulatory drug, excluding topical&#xD;
             treatment (e.g., ointments, nasal sprays), within 30 days prior to signing the&#xD;
             informed consent.&#xD;
&#xD;
         14. The participant is pregnant or lactating at the time of enrollment.&#xD;
&#xD;
         15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia&#xD;
             (including infection, dysplasia).&#xD;
&#xD;
         16. The participant has participated in another clinical study involving another&#xD;
             Investigational product (IP) or investigational device within 30 days prior to&#xD;
             enrollment or is scheduled to participate in another clinical study involving an IP or&#xD;
             investigational device during the course of this study.&#xD;
&#xD;
         17. The participant has a progressive fatal disease and/or life expectancy of less than 15&#xD;
             months.&#xD;
&#xD;
         18. The participant is scheduled for a surgical intervention.&#xD;
&#xD;
         19. The participant is identified by the investigator as being unable or unwilling to&#xD;
             cooperate with study procedures.&#xD;
&#xD;
         20. The participant has a mental condition rendering him/her unable to understand the&#xD;
             nature, scope and possible consequences of the study and/or evidence of an&#xD;
             uncooperative attitude.&#xD;
&#xD;
         21. The participant is in prison or compulsory detention by regulatory and/or juridical&#xD;
             order.&#xD;
&#xD;
         22. The participant is member of the study team or in a dependent relationship with one of&#xD;
             the study team members which includes close relatives (i.e., children, partner/spouse,&#xD;
             siblings and parents) as well as employees.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Health</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bleeding and Clotting Disorders Institute</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Health</name>
      <address>
        <city>Aurora</city>
        <state>Indiana</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Hemophilia and Thrombosis Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Center of Wake Forest Unversity</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences Centre</name>
      <address>
        <city>Hamilton</city>
        <zip>L8N 3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Morvan</name>
      <address>
        <city>Brest</city>
        <state>Finistere</state>
        <zip>29609</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupement Hospitalier Est- Hôpital Louis Pradel</name>
      <address>
        <city>Bron cedex</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU CAEN - Hôpital de la Côte de Nacre</name>
      <address>
        <city>Caen cedex 9</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dijon - Hopital du Bocage</name>
      <address>
        <city>Dijon cedex</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cardiologique - CHU Lille</name>
      <address>
        <city>Lille Cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coagulation Research Centre GmbH</name>
      <address>
        <city>Duisburg</city>
        <zip>47051</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Johann Wolfgang Goethe-Universitaet</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Werlhof-Institut GmbH</name>
      <address>
        <city>Hannover</city>
        <zip>30159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza</name>
      <address>
        <city>Roma</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Pediatrico Bambino Gesù</name>
      <address>
        <city>Roma</city>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Medisch Centrum</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBEI HPE Altai State Medical University of MoH and SD</name>
      <address>
        <city>Barnaul</city>
        <zip>656038</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SAIH &quot;Kemerovo Regional Clinical Hospital&quot;</name>
      <address>
        <city>Kemerovo</city>
        <zip>650066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBI of Science &quot;Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA</name>
      <address>
        <city>Kirov</city>
        <zip>610017</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBI of Science &quot;Kirov Scientific and Research Institute of Hematology and Blood Transfusion of FMBA</name>
      <address>
        <city>Kirov</city>
        <zip>610027</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Alicante</name>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University Medical Faculty</name>
      <address>
        <city>Izmir</city>
        <zip>35040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University Medical Faculty</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ondokuz Mayis Univ. Med. Fac.</name>
      <address>
        <city>Samsun</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f6b5fc34db2bf003ab45955</url>
    <description>To obtain more information on the study, click here/on this link</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <results_first_submitted>July 5, 2021</results_first_submitted>
  <results_first_submitted_qc>August 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 6, 2021</results_first_posted>
  <last_update_submitted>August 5, 2021</last_update_submitted>
  <last_update_submitted_qc>August 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Von Willebrand Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Factor VIII</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02973087/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02973087/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 32 sites in the United States, Canada, France, Germany, Italy, Netherlands, Russia, Spain, and Turkey between 16 November 2017 (first participant first visit) and 06 July 2020 (last participant last visit).</recruitment_details>
      <pre_assignment_details>A total of 29 participants were screened, out of which 6 participants were screen failures and 23 participants were grouped into 2 cohorts: Prior On-demand and Switch (based on the previous von Willebrand disease [VWD] treatment they received prior to the study) and received prophylactic treatment with recombinant von Willebrand factor (rVWF).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Prior On-demand Participants</title>
          <description>Participants who had taken only on-demand von Willebrand factor (VWF) prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 plus minus (+/- ) 10 international unit per kilogram (IU/kg), intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (recombinant Factor VIII [rFVIII]); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
        </group>
        <group group_id="P2">
          <title>Switch Participants</title>
          <description>Participants who had taken prophylactic treatment with plasma derived VWF product (pdVWF) prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>other</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set (SAS) composed of all participants who received any amount of investigational product (IP) (rVWF, vonicog alpha).</population>
      <group_list>
        <group group_id="B1">
          <title>Prior On-demand Participants</title>
          <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
        </group>
        <group group_id="B2">
          <title>Switch Participants</title>
          <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.0" spread="17.6"/>
                    <measurement group_id="B2" value="43.9" spread="21.8"/>
                    <measurement group_id="B3" value="40.6" spread="19.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12</title>
        <description>ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).</description>
        <time_frame>Up to 12 months</time_frame>
        <population>Full analysis set (FAS) composed of all participants who received prophylactic IP treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12</title>
          <description>ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).</description>
          <population>Full analysis set (FAS) composed of all participants who received prophylactic IP treatment.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.085" lower_limit="0.021" upper_limit="0.346"/>
                    <measurement group_id="O2" value="0.550" lower_limit="0.086" upper_limit="3.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12</title>
        <description>For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment. This outcome measure was analyzed only for prior on-demand participants treated for spontaneous BEs.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12</title>
          <description>For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment. This outcome measure was analyzed only for prior on-demand participants treated for spontaneous BEs.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.3" lower_limit="64.0" upper_limit="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12</title>
        <description>For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment. This outcome measure was analyzed only for switch participants treated for spontaneous BEs.</population>
        <group_list>
          <group group_id="O1">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12</title>
          <description>For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment. This outcome measure was analyzed only for switch participants treated for spontaneous BEs.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.0" lower_limit="55.5" upper_limit="99.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12</title>
        <description>The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (&gt;) 0 through 2,&gt;2 through 5,&gt;5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.</description>
        <time_frame>Baseline through Month 12</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12</title>
          <description>The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (&gt;) 0 through 2,&gt;2 through 5,&gt;5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Historical</title>
              <category_list>
                <category>
                  <title>0 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;0 through 2 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;2 through 5 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;5 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>On-Study Through Month 12</title>
              <category_list>
                <category>
                  <title>0 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;0 through 2 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;2 through 5 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;5 BEs</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12</title>
        <description>For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12</title>
          <description>For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment.</population>
          <units>infusions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.1" spread="38.4"/>
                    <measurement group_id="O2" value="87.8" spread="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12</title>
        <description>Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12</title>
          <description>Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment.</population>
          <units>infusions per week</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.88" spread="0.7"/>
                    <measurement group_id="O2" value="1.85" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12</title>
        <description>For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram [kg]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12</title>
          <description>For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram [kg]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment.</population>
          <units>IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3431.584" spread="2117.6562"/>
                    <measurement group_id="O2" value="4433.752" spread="1844.8761"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12</title>
        <description>Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.</description>
        <time_frame>Up to 12 months</time_frame>
        <population>FAS composed of all participants who received prophylactic IP treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12</title>
          <description>Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.</description>
          <population>FAS composed of all participants who received prophylactic IP treatment.</population>
          <units>number of BEs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Oral and other mucosa</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Menorrhagia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemarthrosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs</title>
        <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.</description>
        <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs</title>
          <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants With TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Based on Severity of TEAEs</title>
        <description>An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.</description>
        <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Based on Severity of TEAEs</title>
          <description>An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With TEAEs Based Causality</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.</description>
        <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With TEAEs Based Causality</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Thromboembolic Events</title>
        <description>Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.</description>
        <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Thromboembolic Events</title>
          <description>Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Hypersensitivity Reactions</title>
        <description>Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.</description>
        <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Hypersensitivity Reactions</title>
          <description>Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)</title>
        <description>Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.</description>
        <time_frame>Baseline through Month 12</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)</title>
          <description>Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)</title>
        <description>The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.</description>
        <time_frame>Baseline through Month 12</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)</title>
          <description>The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin</title>
        <description>Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.</description>
        <time_frame>Baseline through Month 12</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin</title>
          <description>Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</title>
        <description>Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.</description>
        <time_frame>Baseline up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</title>
          <description>Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters</title>
        <description>Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.</description>
        <time_frame>Baseline up to end of study (approximately 32 months)</time_frame>
        <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters</title>
          <description>Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.</description>
          <population>SAS composed of all participants who received any amount of IP (rVWF, vonicog alpha).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram ([IU/dL]/[IU/kg]).</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PK full analysis set (PKFAS) composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram ([IU/dL]/[IU/kg]).</description>
          <population>PK full analysis set (PKFAS) composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>(IU/dL)/(IU/kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.463" spread="0.3205"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>IR based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>IR based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>(IU/dL)/(IU/kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.699" spread="0.3488"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>(IU/dL)/(IU/kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.405" spread="0.5737"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.98" lower_limit="9.01" upper_limit="45.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.81" lower_limit="12.6" upper_limit="39.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.64" lower_limit="12.8" upper_limit="29.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.27" spread="11.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.55" spread="9.777"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.39" spread="6.860"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units*hour per deciliter (IU*h/dL).</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units*hour per deciliter (IU*h/dL).</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1199" spread="467.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2578" spread="1067"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3010" spread="1221"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="919.8" spread="378.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2357" spread="848.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2824" spread="1112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.62" spread="16.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Cmax based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Cmax based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.1" spread="19.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Cmax based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Cmax based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="120.74" spread="29.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Tmax based on VWF:Rco activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Tmax based on VWF:Rco activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.540" lower_limit="0.27" upper_limit="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Tmax based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Tmax based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="0.27" upper_limit="3.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Tmax based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Tmax based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.500" lower_limit="0.27" upper_limit="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>deciliter per kilogram (dL/kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.052" spread="0.4981"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>dL/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6860" spread="0.1556"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>dL/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4889" spread="0.1371"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>dL/kg/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04765" spread="0.01620"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>dL/kg/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02185" spread="0.006821"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>dL/kg/h</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01872" spread="0.005946"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.8" spread="32.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.055" lower_limit="11.98" upper_limit="46.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
        <time_frame>At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for prior on-demand participants.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4949" spread="2436"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1561" spread="1298"/>
                    <measurement group_id="O2" value="1662" spread="675.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2908" spread="1372"/>
                    <measurement group_id="O2" value="3196" spread="838.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3445" spread="1914"/>
                    <measurement group_id="O2" value="4276" spread="1471"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.63" spread="37.05"/>
                    <measurement group_id="O2" value="102.89" spread="44.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.1" spread="39.6"/>
                    <measurement group_id="O2" value="107.1" spread="37.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="137.48" spread="44.97"/>
                    <measurement group_id="O2" value="162.19" spread="60.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.330" lower_limit="0.25" upper_limit="1.25"/>
                    <measurement group_id="O2" value="0.400" lower_limit="0.33" upper_limit="0.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.580" lower_limit="0.28" upper_limit="1.17"/>
                    <measurement group_id="O2" value="0.330" lower_limit="0.23" upper_limit="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.420" lower_limit="0.28" upper_limit="3.00"/>
                    <measurement group_id="O2" value="0.670" lower_limit="0.33" upper_limit="3.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
        <description>Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity</title>
          <description>Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Data not reported as value was below the limit of quantification.</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Data not reported as value was below the limit of quantification.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
        <description>Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity</title>
          <description>Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="4.8"/>
                    <measurement group_id="O2" value="11.7" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
        <description>Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity</title>
          <description>Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.82" spread="6.86"/>
                    <measurement group_id="O2" value="9.94" spread="8.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU*h/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5984" spread="2490"/>
                    <measurement group_id="O2" value="5836" spread="1735"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104.1" spread="35.1"/>
                    <measurement group_id="O2" value="75.7" spread="37.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.500" lower_limit="6.17" upper_limit="29.27"/>
                    <measurement group_id="O2" value="24.070" lower_limit="1.08" upper_limit="30.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
        <description>Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity</title>
          <description>Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.</description>
          <population>PKFAS composed of all participants who received at least one IP infusion and who provided at least one quantifiable pharmacokinetic or pharmacodynamic post dose measurement for pharmacokinetic and/or pharmacodynamics analysis. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.8" spread="8.6"/>
                    <measurement group_id="O2" value="22.9" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Factor VIII (FVIII) Clotting Activity</title>
        <description>FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.</description>
        <time_frame>At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours</time_frame>
        <population>FAS will be composed of all participants who receive prophylactic IP treatment. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure and &quot;number analyzed&quot; were participants who were evaluable for the outcome measure at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Prior On-demand Participants</title>
            <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
          <group group_id="O2">
            <title>Switch Participants</title>
            <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
          </group>
        </group_list>
        <measure>
          <title>Factor VIII (FVIII) Clotting Activity</title>
          <description>FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.</description>
          <population>FAS will be composed of all participants who receive prophylactic IP treatment. Here &quot;overall number of participants analyzed&quot; were participants who were evaluable for this outcome measure and &quot;number analyzed&quot; were participants who were evaluable for the outcome measure at given time points.</population>
          <units>IU/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.1" spread="23.5"/>
                    <measurement group_id="O2" value="28.0" spread="21.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 minutes post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.7" spread="22.5"/>
                    <measurement group_id="O2" value="30.9" spread="18.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 minutes post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.1" spread="21.5"/>
                    <measurement group_id="O2" value="33.4" spread="19.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.0" spread="24.3"/>
                    <measurement group_id="O2" value="34.0" spread="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.2" spread="23.4"/>
                    <measurement group_id="O2" value="48.4" spread="20.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.4" spread="25.1"/>
                    <measurement group_id="O2" value="69.3" spread="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.3" spread="25.0"/>
                    <measurement group_id="O2" value="78.0" spread="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" spread="36.5"/>
                    <measurement group_id="O2" value="93.8" spread="17.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.4" spread="32.6"/>
                    <measurement group_id="O2" value="90.6" spread="15.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.8" spread="29.1"/>
                    <measurement group_id="O2" value="79.2" spread="17.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.8" spread="37.8"/>
                    <measurement group_id="O2" value="44.6" spread="18.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>96 hours post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" spread="23.5"/>
                    <measurement group_id="O2" value="16.0" spread="11.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug up to end of study (approximately 32 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Prior On-demand Participants</title>
          <description>Participants who had taken only on-demand VWF prior to the current study received rVWF (vonicog alpha) initial prophylactic treatment at a dose range of 50 +/- 10 IU/kg, intravenous infusion, twice per week for a planned period of 12 months. Dose escalation to higher dose (up to 80 IU/kg per infusion) or frequency (up to 3 times a week) was based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
        </group>
        <group group_id="E2">
          <title>Switch Participants</title>
          <description>Participants who had taken prophylactic treatment with pdVWF prior to current study and switched to prophylaxis with rVWF (vonicog alpha) during the study for a planned period of 12 months; received rVWF twice weekly at an initial prophylactic dose of +/- 10 percent (%) of VWF in the pdVWF weekly dose received prior to this study. Dosing with rVWF up to 80 IU/kg per infusion or at a frequency up to 3 times a week or once a week were allowed depending on the total weekly dose and the dosing regimen used in their previous pdVWF prophylaxis regimen and based on medical indication and investigator judgment. During this prophylactic treatment period, any breakthrough bleeding episodes requiring replacement therapy with VWF concentrate was treated with rVWF with or without ADVATE (rFVIII); the dose was determined according to the bleeding type and severity, and was adjusted based on the participant's clinical response.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Multiple injuries</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rheumatoid arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Ventricular extrasystoles</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Herpes virus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Increased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Iron deficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vitamin B12 deficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Seronegative arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Takeda</organization>
      <phone>+1-877-825-3327</phone>
      <email>TrialDisclosures@takeda.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02973087
org study id: 071301
secondary id: 2016-001478-14
nct id: NCT02973087
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this phase 3 study is to investigate the efficacy and safety, including
      immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics
      (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment
      with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with
      severe von Willebrand disease (VWD).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12
time frame: Up to 12 months
description: ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug. On-study observation period started on the day of first administration of study drug and continuing through the date of completion/discontinuation from study. The comparison of the two ABRs (on-study and historical) for spontaneous bleeding episodes (not related to trauma) during prophylactic treatment with rVWF was reported as a ratio of mean ABRs (on-study ABR:historical ABR).
measure: Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12
time frame: Up to 12 months
description: For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.
measure: Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12
time frame: Up to 12 months
description: For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.
measure: Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12
time frame: Baseline through Month 12
description: The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (>) 0 through 2,>2 through 5,>5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug. The baseline sABR for treated BEs was based on historical BE data and on-study sABR was based on treated spontaneous BEs during prophylaxis with rVWF through Month 12. On-study observation period started on the day of first administration of study drug continuing through the date of completion/discontinuation from study. Number of participants based on categorized sABR was calculated and reported.
measure: Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12
time frame: Up to 12 months
description: For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.
measure: Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12
time frame: Up to 12 months
description: Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.
measure: Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12
time frame: Up to 12 months
description: For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram [kg]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.
measure: Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12
time frame: Up to 12 months
description: Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
time frame: From first dose of study drug up to end of study (approximately 32 months)
description: An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.
measure: Number of Participants Based on Severity of TEAEs
time frame: From first dose of study drug up to end of study (approximately 32 months)
description: An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required therapeutic intervention. Participants were counted by considering the maximum severity of TEAEs.
measure: Number of Participants With TEAEs Based Causality
time frame: From first dose of study drug up to end of study (approximately 32 months)
description: An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE was defined as any TEAE indicated as 'possibly related' or 'probably related'. Number of participants with TEAEs based causality was reported.
measure: Number of Participants With Thromboembolic Events
time frame: From first dose of study drug up to end of study (approximately 32 months)
description: Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.
measure: Number of Participants With Hypersensitivity Reactions
time frame: From first dose of study drug up to end of study (approximately 32 months)
description: Hypersensitivity (also called hypersensitivity reaction or intolerance) defined as undesirable reactions produced by the normal immune system, including allergies and autoimmunity. Potential hypersensitivity events were identified by broad search criteria and then medically assessed. Number of participants with hypersensitivity reactions as TEAEs of special interest was calculated.
measure: Number of Participants Who Developed Neutralizing Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
time frame: Baseline through Month 12
description: Three functional VWF assays for von Willebrand factor collagen binding (VWF:CB), von Willebrand factor: Ristocetin Cofactor (VWF:RCo) and von Willebrand factor VIII B (VWF:FVIIIB) were used to test the presence of neutralizing anti-VWF antibodies. Neutralizing antibodies to VWF:RCo, VWF:CB and VWF:FVIIIB activities was measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). Only confirmed neutralizing anti -VWF antibodies were considered inhibitors. Number of participants who developed neutralizing antibodies to rVWF and FVIII were assessed.
measure: Number of Participants Who Developed of Total Binding Antibodies to Von Willebrand Factor (rVWF) and Factor VIII (FVIII)
time frame: Baseline through Month 12
description: The presence of total binding anti-VWF antibodies was determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human Immunoglobulin (Ig) antibodies (IgG, IgM and IgA). Binding antibodies against FVIII was analyzed using a proprietary enzyme immunoassay. Number of participants who developed of total binding antibodies to rVWF and FVIII was assessed.
measure: Number of Participants Who Developed Binding Antibodies to Chinese Hamster Ovary (CHO) Proteins, Mouse Immunoglobulin G (IgG) and/or rFurin
time frame: Baseline through Month 12
description: Total Ig antibodies (IgG, IgA, IgM) against CHO protein and human furin was analyzed using ELISA. For detection and quantification of IgG antibodies originating from human plasma that were directed against mouse-IgG (HAMA: human anti- mouse antibodies) was assessed using ELISA (Medac, Hamburg, Germany). Number of participants who developed binding antibodies to CHO proteins, Mouse IgG and/or rFurin was assessed.
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
time frame: Baseline up to end of study (approximately 32 months)
description: Vital signs included blood pressure (systolic and diastolic), pulse rate, respiratory rate and body temperature. Number of participants with clinically significant change from baseline in vital signs was assessed.
measure: Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Parameters
time frame: Baseline up to end of study (approximately 32 months)
description: Clinical laboratory parameters included hematology and clinical chemistry assessments. Number of participants with clinically significant change from baseline in clinical laboratory parameters was assessed.
measure: Pharmacokinetic (PK) Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: IR at the maximum plasma concentration of VWF:RCo activity at initial PK assessment was reported. Unit of measure: International Units per deciliter/International Units per kilogram ([IU/dL]/[IU/kg]).
measure: Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: IR based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Incremental Recovery (IR) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: IR at the maximum plasma concentration of VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Rco activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Terminal Half-life (T1/2) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: T1/2 defined as the time in hours required for the concentration of the drug to reach half of its original value. T1/2 based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Rco activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Mean Residence Time (MRT) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: MRT was calculated as (AUMC0-∞/AUC0-∞) - T1/2 where T1 represented the time duration of infusion, where AUMC represented the area under the first moment curve. MRT based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-∞ based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: International Units*hour per deciliter (IU*h/dL).
measure: Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-∞ based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-∞ based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tlast based on VWF:Rco activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tlast based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tlast based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax based on VWF:Rco at initial PK assessment was reported. Unit of measure: International Units per deciliter (IU/dL).
measure: Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Maximum Plasma Concentration (Cmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax based on VWF:Rco activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Rco activity at initial assessment was reported.
measure: Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:Ag activity at initial assessment was reported.
measure: Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss based on VWF:CB activity at initial assessment was reported.
measure: Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Rco activity at initial PK assessment was reported. Unit of measure: deciliter per kilogram per hour (dL/kg/h).
measure: Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:Ag activity at initial PK assessment was reported.
measure: Pharmacokinetic Assessment: Clearance (CL) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL based on VWF:CB activity at initial PK assessment was reported.
measure: Pharmacodynamic (PD) Assessment: Maximum Plasma Concentration (Cmax) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
measure: Pharmacodynamic Assessment: Minimum Time to Reach the Maximum Plasma Concentration (Tmax) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
measure: Pharmacodynamic Assessment: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration (AUC0-tlast) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At baseline: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tlast based on FVIII:C activity at initial PD assessment by the 1-stage clotting assay was reported.
measure: Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tau;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tau;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tau;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax;ss based on VWF:Ag activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor: Ristocetin Cofactor (VWF:Rco) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Antigen (VWF:Ag) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmin;ss based on VWF:Rco activity at steady state during end of study (Month 12) was reported.
measure: Pharmacokinetics Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Von Willebrand Factor Collagen Binding (VWF:CB) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmin;ss based on VWF:CB activity at steady state during end of study (Month 12) was reported.
measure: Pharmacodynamic Assessment at Steady State: Area Under the Plasma Concentration Versus Time Curve From Time 0 to End of the Partial Dosing Interval (AUC0- Tau;ss) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: AUC0-tau;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
measure: Pharmacodynamic Assessment at Steady State: Maximum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmax;ss based on FVIII:C activity was assessed at steady state during end of study (Month 12) was reported.
measure: Pharmacodynamic Assessment at Steady State: Minimum Time to Reach the Maximum Plasma Concentration at Steady State (Tmax;ss) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Tmax;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
measure: Pharmacodynamic Assessment at Steady State: Minimum Plasma Concentration During the Partial Dosing Interval at Steady State (Cmin;ss) Based on Factor VIII Clotting (FVIII:C) Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: Cmin;ss based on FVIII:C activity at steady state during end of study (Month 12) was reported.
measure: Factor VIII (FVIII) Clotting Activity
time frame: At Month 12: Within 30 minutes pre-infusion; and post-infusion at 15, 30 minutes and 1, 3, 6, 12, 24, 30, 48, 72, and 96 hours
description: FVIII clotting activity (FVIII:C) levels was assessed and reported as per pre-specified PK time points at Month 12.
arm group label: All Study Participants
arm group type: Experimental
description: Participants will receive prophylaxis with rVWF in two cohorts: on-demand (OD) cohort (previously treated with OD) and pdVWF switch cohort (participants switching from prophylactic treatment with pdVWF).
intervention type: Biological
intervention name: von Willebrand factor (Recombinant)
description: OD participants will receive intravenous (IV) rVWF:RCo at an initial prophylactic dose of 50 +/- 10 International Unit per Kilogram (IU/kg) twice (two infusions) a week for at least 12 months up to 15 months and may be increased up to 80 IU/kg. pdVWF switch cohort participants will receive rVWF:RCo equivalent (± 10%) to the weekly VWF dose received during prophylactic treatment with pdVWF.
arm group label: All Study Participants
other name: BAX 111
other name: rVWF
other name: VONVENDI
other name: vonicog alfa
other name: BAX111
intervention type: Biological
intervention name: Antihemophilic Factor (Recombinant)
description: During prophylaxis period any bleeding episodes requiring substitution therapy with VWF concentrate to control bleeding will be treated with rVWF with or without ADVATE. Participants will receive rFVIII IV if necessary for OD treatment of breakthrough bleeds or for peri-operative. The dose will be according to the bleeding type and severity and it will be adjusted to the clinical response.
arm group label: All Study Participants
other name: ADVATE
other name: Recombinant Factor VIII
other name: rFVIII
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: France
country: Germany
country: Italy
country: Netherlands
country: Russian Federation
country: Spain
country: Turkey
country: United States
url: https://clinicaltrials.takeda.com/study-detail/5f6b5fc34db2bf003ab45955
description: To obtain more information on the study, click here/on this link
responsible party type: Sponsor
mesh term: Von Willebrand Diseases
mesh term: Factor VIII
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 