<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/NCT03275454</url>
  </required_header>
  <id_info>
    <org_study_id>TDR16218</org_study_id>
    <secondary_id>BIVV009-201</secondary_id>
    <nct_id>NCT03275454</nct_id>
  </id_info>
  <brief_title>A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple- Dose BIVV009 in Participants With Chronic Immune Thrombocytopenia (ITP)</brief_title>
  <official_title>A Phase 1 Safety, Tolerability, and Pharmacokinetics &amp; Pharmacodynamics Study of Multiple- Dose BIVV009 in Patients With Chronic Immune Thrombocytopenia (ITP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioverativ, a Sanofi company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</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 study is to explore the safety, preliminary clinical benefit, and&#xD;
      activity of BIVV009 in patients with chronic immune thrombocytopenia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Actual">February 16, 2021</completion_date>
  <primary_completion_date type="Actual">February 16, 2021</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Premature Study Terminations</measure>
    <time_frame>Approximately 97 weeks</time_frame>
    <description>Number of participants with premature study terminations will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Clinical Laboratory Abnormalities</measure>
    <time_frame>Approximately 97 weeks</time_frame>
    <description>Clinical laboratory abnormalities including one or more specific target-organs for toxicity of BIVV009, abnormalities in D-dimer, thrombin-anti-thrombin assay, and Systemic Lupus Erythematosus (SLE) panel.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT)</measure>
    <time_frame>Baseline and A-EOT (Day 147)</time_frame>
    <description>Change from baseline in peripheral blood platelet count at A-EOT will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment</measure>
    <time_frame>Baseline up to Day 147</time_frame>
    <description>Change from baseline in peripheral blood platelet count during BIVV009 treatment will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Number of Participants who are independent from using combination Immune Thrombocytopenia (ITP) therapy during A-EOT but receive combination ITP therapy after A-EOT</measure>
    <time_frame>Day 147 (A-EOT) up to Day 196 (EOS)</time_frame>
    <description>Number of participants who are independent from using combination ITP therapy during A-EOT but receive combination ITP therapy after A-EOT will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Number of Participants who Achieve Complete Response Through A-EOT</measure>
    <time_frame>Up to Day 147</time_frame>
    <description>Complete response (CR) is defined as a platelet count greater than or equal to (&gt;=) 100*10^9/liter (L) measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Number of Participants who Achieve Response Through A-EOT</measure>
    <time_frame>Up to Day 147</time_frame>
    <description>Response or Better: Response (R) is defined as a platelet count &gt;= 30*10^9/L and a greater than 2-fold increase from baseline measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits; and CR: A platelet count &gt;=100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Duration of Complete Response per Each CR</measure>
    <time_frame>Up to Day 196</time_frame>
    <description>Duration of CR is defined as the number of consecutive days in which a patient's peripheral blood platelet count is &gt;= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Duration of Response per Each Response</measure>
    <time_frame>Up to Day 196</time_frame>
    <description>Duration of response is defined as the number of consecutive days in which a patient's peripheral blood platelet count is &gt;= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Time to First Platelet Response</measure>
    <time_frame>Up to Day 196</time_frame>
    <description>Time to first platelet response is defined as greater than or equal to 30*10^9/L, 50*10^9/L, 100*10^9/L (confirmed by a consecutive platelet response at least 7 days apart).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response</measure>
    <time_frame>Up to Day 196</time_frame>
    <description>Number of participants who report loss of response among those who achieve response will be reported. For a participant with a response (R), the loss of the response is defined as a platelet count &lt; 30*10^9/L measured on 2 consecutive occasions at least 1 day apart, or a less than 2-fold increase in platelet count from baseline measured on 2 consecutive occasions at least 1 day apart, or the presence of bleeding, or use of the combination ITP therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response</measure>
    <time_frame>Up to Day 196</time_frame>
    <description>Number of participants who report loss of complete response among those who achieve complete response will be reported. For a participant with a complete response (CR), loss of complete response is defined as a platelet count less than (&lt;) 100*10^9/L measured on 2 consecutive occasions more than 1 day apart and/or the presence of bleeding or use of the combination ITP therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT</measure>
    <time_frame>Baseline up to 52 weeks</time_frame>
    <description>Change from baseline (Part B) in peripheral blood platelet count to B-EOT will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of participants who achieve CR and the lack of platelet transfusions or other ITP therapy during Part B treatment period will be reported. Complete response (CR): A platelet count &gt;= 100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT)</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of participants who achieve response through B-EOT will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Duration of Complete Response per Each CR</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Duration of CR is defined as the number of consecutive days in which a participant's peripheral blood platelet count is &gt;= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Duration of Response per each Response</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Duration of response is defined as the number of consecutive days in which a participant's peripheral blood platelet count is &gt;= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who achieve a platelet count &gt;= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of participants who achieve a platelet count &gt;= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who achieve a platelet count &gt;=30*10^9/L, a &gt;2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart, have absence of bleeding on and through these two visits, use any combination ITP therapy</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of participants who achieve a platelet count &gt;= 30*10^9/L and a greater than (&gt;) 2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of Participants who do not require other ITP therapy (non-transfusion) following the last BIVV009 dose will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of Participants who do not require platelet transfusions during the Part B treatment period will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Number of participants who experience any bleeding episode, bleeding by grade or serious bleeding according to the International Working Group (IWG) Bleeding Assessment Tool (BAT) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentrations of BIVV009</measure>
    <time_frame>Approximately 97 weeks</time_frame>
    <description>Plasma concentrations of BIVV009 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of BIVV009</measure>
    <time_frame>Approximately 97 weeks</time_frame>
    <description>Maximum observed concentration of BIVV009 in plasma will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009</measure>
    <time_frame>Approximately 97 weeks</time_frame>
    <description>Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009</measure>
    <time_frame>Approximately 97 weeks</time_frame>
    <description>AUC (0-t) is the area under the Concentration-time curve (AUC) from hour 0 to the last quantifiable time point of BIVV009.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>Blood samples will be collected to determine number of participants with anti-drug antibodies (ADAs) against BIVV009.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complement System Classical Pathway Levels as Measured by WIESLAB Assay</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>Inhibition by BIVV009 of the complement system classical pathway measured by the WIESLAB assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Complement (CH50) Levels</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity. It will be assessed using complement assays.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Complement Factor C4 Levels</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>Total C4 Levels will be assessed in plasma using complement assays.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C1 Complex Components: C1q</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>C1q Levels will be assessed in plasma using complement assays.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thrombopoietin Level</measure>
    <time_frame>Up to 97 weeks</time_frame>
    <description>Thrombopoietin level will be assessed in plasma using complement assays.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Purpura, Thrombocytopenic, Idiopathic</condition>
  <arm_group>
    <arm_group_label>BIVV009</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009 intravenous (IV) infusion and participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009 every 2 weeks for approximately 21 weeks in Part A (based on time to complete 11 doses of study drug). There will be a 9-week safety follow-up/washout period after administration of the last dose of study drug in Part A. Participants who have been shown to benefit from BIVV009 treatment during Part A, will receive BIVV009 (based on weight) biweekly for up to 52 weeks of BIVV009 after Last Patient In (LPI) in part B.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIVV009 6.5 grams</intervention_name>
    <description>Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009.</description>
    <arm_group_label>BIVV009</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIVV009 7.5 grams</intervention_name>
    <description>Participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009.</description>
    <arm_group_label>BIVV009</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Part A:&#xD;
&#xD;
          -  Chronic immune thrombocytopenia (ITP) (ITP lasting for greater than or equal to ([&gt;=]&#xD;
             12 months) as defined in the protocol&#xD;
&#xD;
          -  Normal prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT)&#xD;
&#xD;
          -  No history of a coagulation disorder&#xD;
&#xD;
          -  Hemoglobin level greater than (&gt;) 10 gram per deciliter (g/dL) (following blood&#xD;
             transfusion is acceptable) and normal white blood cell (WBC) and neutrophil counts&#xD;
             (elevated WBC/absolute neutrophil count [ANC] attributed to steroid treatment is&#xD;
             acceptable)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status grade less than or equal&#xD;
             to (&lt;=) 2&#xD;
&#xD;
          -  Documented vaccinations against encapsulated bacterial pathogens (Neisseria&#xD;
             meningitis, including serogroup B meningococcus [where available], Haemophilus&#xD;
             influenzae, and Streptococcus pneumoniae) within 5 years of enrollment&#xD;
&#xD;
          -  Adequate intravenous (IV) access&#xD;
&#xD;
        Part B:&#xD;
&#xD;
          -  Able to comprehend and to give informed consent for Part B&#xD;
&#xD;
          -  History of ITP and previously treated with at least 1 dose of BIVV009 in Part A&#xD;
&#xD;
          -  Evidence of treatment efficacy to BIVV009 as defined by a platelet count &gt; 30*10^9/L&#xD;
             on at least 1 occasion OR a doubling of the platelet count from baseline&#xD;
&#xD;
          -  Participants who have completed the 21-week Part A treatment period but have not&#xD;
             reached the Part A End of Study (EOS) visit must have evidence of ongoing or recurrent&#xD;
             thrombocytopenia during the Part A safety follow-up/washout period as demonstrated by&#xD;
             a platelet count less than (&lt;) 50*10^9/L or a &gt;= 50 percent (%) decrease in platelet&#xD;
             count over &lt; 1 week&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Part A:&#xD;
&#xD;
          -  Clinically significant medical history or ongoing chronic illness that would&#xD;
             jeopardize the safety of the participant or compromise the quality of the data derived&#xD;
             from his/her participation in this study&#xD;
&#xD;
          -  Clinically relevant infection of any kind within the preceding month of enrollment&#xD;
&#xD;
          -  History of venous or arterial thrombosis within the preceding year of enrollment&#xD;
&#xD;
          -  Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants&#xD;
             within 1 week of enrollment&#xD;
&#xD;
          -  Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune&#xD;
             disorders associated with anti-nuclear antibodies (ANAs) including those that are&#xD;
             medically controlled, at Screening (other than ITP)&#xD;
&#xD;
          -  Secondary immune thrombocytopenia from any cause including lymphoma, chronic&#xD;
             lymphocytic leukemia, and drug-induced thrombocytopenia&#xD;
&#xD;
          -  Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C&#xD;
             virus antibody) prior to or at Screening&#xD;
&#xD;
          -  Positive human immunodeficiency virus (HIV) test result prior to or at Screening&#xD;
&#xD;
        Part B:&#xD;
&#xD;
          -  Presence of unacceptable side effects or toxicity associated with BIVV009 (including&#xD;
             prior hypersensitivity reactions to BIVV009) such that there is an unfavorable&#xD;
             risk-benefit assessment for continued treatment with BIVV009 in the opinion of the&#xD;
             Investigator and/or Sponsor&#xD;
&#xD;
          -  For participants who have completed the 9-week safety follow-up/washout period and&#xD;
             final study visit before entry into Part B, a positive hepatitis panel (including&#xD;
             hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at&#xD;
             Screening. Patients who have undergone hepatitis C antiviral therapy may be allowed if&#xD;
             they are documented to be negative for hepatitis C virus ribonucleic acid (RNA) on at&#xD;
             least 2 occasions separated by at least 3 months (including 1 RNA test at least 6&#xD;
             months after completion of antiviral therapy) and are also negative for hepatitis C&#xD;
             virus RNA at Screening&#xD;
&#xD;
          -  Use of prescribed or over-the-counter medications, supplements, vitamins, and/or&#xD;
             herbal remedies within 2 weeks before the first dose of BIVV009 in Part B, which in&#xD;
             the judgment of the Investigator may adversely affect the participants welfare or the&#xD;
             integrity of the study results (excluding hormonal contraception in female&#xD;
             participants)&#xD;
&#xD;
          -  If previously treated with rituximab, the last dose of rituximab was administered &lt; 12&#xD;
             weeks before the first dose of BIVV009 in Part B&#xD;
&#xD;
          -  Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune&#xD;
             disorders associated with anti-nuclear antibodies (ANA), including those that are&#xD;
             medically controlled, at Screening (other than ITP). Positive ANAs at screening that&#xD;
             are not associated with an autoimmune disorder (other than ITP) may be allowed if&#xD;
             present for &gt;= 28 days without associated clinically relevant symptoms&#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>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgetown Lombardi Comprehensive Cancer Center</name>
      <address>
        <city>Georgetown</city>
        <state>District of Columbia</state>
        <zip>20057</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital - Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Essen University Hospital Department of Hematology</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College Hospital</name>
      <address>
        <city>London</city>
        <zip>WC1E 6HX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Broome CM, Roth A, Kuter DJ, Scully M, Smith R, Wang J, Reuter C, Hobbs W, Daak A. Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia. Blood Adv. 2023 Mar 28;7(6):987-996. doi: 10.1182/bloodadvances.2021006864.</citation>
    <PMID>35973190</PMID>
  </results_reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 16, 2023</last_update_submitted>
  <last_update_submitted_qc>May 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Autoimmune Diseases</keyword>
  <keyword>Hematologic Diseases</keyword>
  <keyword>Immune System Diseases</keyword>
  <keyword>Blood Platelet Disorders</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Purpura</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic, Idiopathic</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03275454
org study id: TDR16218
secondary id: BIVV009-201
nct id: NCT03275454
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to explore the safety, preliminary clinical benefit, and
      activity of BIVV009 in patients with chronic immune thrombocytopenia.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: Up to 97 weeks
description: An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
measure: Number of Participants With Premature Study Terminations
time frame: Approximately 97 weeks
description: Number of participants with premature study terminations will be assessed.
measure: Number of Participants With Clinical Laboratory Abnormalities
time frame: Approximately 97 weeks
description: Clinical laboratory abnormalities including one or more specific target-organs for toxicity of BIVV009, abnormalities in D-dimer, thrombin-anti-thrombin assay, and Systemic Lupus Erythematosus (SLE) panel.
measure: Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT)
time frame: Baseline and A-EOT (Day 147)
description: Change from baseline in peripheral blood platelet count at A-EOT will be assessed.
measure: Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment
time frame: Baseline up to Day 147
description: Change from baseline in peripheral blood platelet count during BIVV009 treatment will be assessed.
measure: Part A: Number of Participants who are independent from using combination Immune Thrombocytopenia (ITP) therapy during A-EOT but receive combination ITP therapy after A-EOT
time frame: Day 147 (A-EOT) up to Day 196 (EOS)
description: Number of participants who are independent from using combination ITP therapy during A-EOT but receive combination ITP therapy after A-EOT will be assessed.
measure: Part A: Number of Participants who Achieve Complete Response Through A-EOT
time frame: Up to Day 147
description: Complete response (CR) is defined as a platelet count greater than or equal to (>=) 100*10^9/liter (L) measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
measure: Part A: Number of Participants who Achieve Response Through A-EOT
time frame: Up to Day 147
description: Response or Better: Response (R) is defined as a platelet count >= 30*10^9/L and a greater than 2-fold increase from baseline measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits; and CR: A platelet count >=100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
measure: Part A: Duration of Complete Response per Each CR
time frame: Up to Day 196
description: Duration of CR is defined as the number of consecutive days in which a patient's peripheral blood platelet count is >= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
measure: Part A: Duration of Response per Each Response
time frame: Up to Day 196
description: Duration of response is defined as the number of consecutive days in which a patient's peripheral blood platelet count is >= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
measure: Part A: Time to First Platelet Response
time frame: Up to Day 196
description: Time to first platelet response is defined as greater than or equal to 30*10^9/L, 50*10^9/L, 100*10^9/L (confirmed by a consecutive platelet response at least 7 days apart).
measure: Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response
time frame: Up to Day 196
description: Number of participants who report loss of response among those who achieve response will be reported. For a participant with a response (R), the loss of the response is defined as a platelet count < 30*10^9/L measured on 2 consecutive occasions at least 1 day apart, or a less than 2-fold increase in platelet count from baseline measured on 2 consecutive occasions at least 1 day apart, or the presence of bleeding, or use of the combination ITP therapy.
measure: Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response
time frame: Up to Day 196
description: Number of participants who report loss of complete response among those who achieve complete response will be reported. For a participant with a complete response (CR), loss of complete response is defined as a platelet count less than (<) 100*10^9/L measured on 2 consecutive occasions more than 1 day apart and/or the presence of bleeding or use of the combination ITP therapy.
measure: Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT
time frame: Baseline up to 52 weeks
description: Change from baseline (Part B) in peripheral blood platelet count to B-EOT will be assessed.
measure: Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period
time frame: Up to 52 weeks
description: Number of participants who achieve CR and the lack of platelet transfusions or other ITP therapy during Part B treatment period will be reported. Complete response (CR): A platelet count >= 100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
measure: Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT)
time frame: Up to 52 weeks
description: Number of participants who achieve response through B-EOT will be reported.
measure: Part B: Duration of Complete Response per Each CR
time frame: Up to 52 weeks
description: Duration of CR is defined as the number of consecutive days in which a participant's peripheral blood platelet count is >= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
measure: Part B: Duration of Response per each Response
time frame: Up to 52 weeks
description: Duration of response is defined as the number of consecutive days in which a participant's peripheral blood platelet count is >= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
measure: Part B: Number of Participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT
time frame: Up to 52 weeks
description: Number of participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.
measure: Part B: Number of Participants who achieve a platelet count >=30*10^9/L, a >2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart, have absence of bleeding on and through these two visits, use any combination ITP therapy
time frame: Up to 52 weeks
description: Number of participants who achieve a platelet count >= 30*10^9/L and a greater than (>) 2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.
measure: Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period
time frame: Up to 52 weeks
description: Number of Participants who do not require other ITP therapy (non-transfusion) following the last BIVV009 dose will be assessed.
measure: Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period
time frame: Up to 52 weeks
description: Number of Participants who do not require platelet transfusions during the Part B treatment period will be reported.
measure: Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding
time frame: Up to 52 weeks
description: Number of participants who experience any bleeding episode, bleeding by grade or serious bleeding according to the International Working Group (IWG) Bleeding Assessment Tool (BAT) will be reported.
measure: Plasma Concentrations of BIVV009
time frame: Approximately 97 weeks
description: Plasma concentrations of BIVV009 will be assessed.
measure: Maximum Observed Plasma Concentration (Cmax) of BIVV009
time frame: Approximately 97 weeks
description: Maximum observed concentration of BIVV009 in plasma will be assessed.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009
time frame: Approximately 97 weeks
description: Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 will be assessed.
measure: Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009
time frame: Approximately 97 weeks
description: AUC (0-t) is the area under the Concentration-time curve (AUC) from hour 0 to the last quantifiable time point of BIVV009.
measure: Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009
time frame: Up to 97 weeks
description: Blood samples will be collected to determine number of participants with anti-drug antibodies (ADAs) against BIVV009.
measure: Complement System Classical Pathway Levels as Measured by WIESLAB Assay
time frame: Up to 97 weeks
description: Inhibition by BIVV009 of the complement system classical pathway measured by the WIESLAB assay.
measure: Total Complement (CH50) Levels
time frame: Up to 97 weeks
description: Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity. It will be assessed using complement assays.
measure: Total Complement Factor C4 Levels
time frame: Up to 97 weeks
description: Total C4 Levels will be assessed in plasma using complement assays.
measure: C1 Complex Components: C1q
time frame: Up to 97 weeks
description: C1q Levels will be assessed in plasma using complement assays.
measure: Thrombopoietin Level
time frame: Up to 97 weeks
description: Thrombopoietin level will be assessed in plasma using complement assays.
arm group label: BIVV009
arm group type: Experimental
description: Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009 intravenous (IV) infusion and participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009 every 2 weeks for approximately 21 weeks in Part A (based on time to complete 11 doses of study drug). There will be a 9-week safety follow-up/washout period after administration of the last dose of study drug in Part A. Participants who have been shown to benefit from BIVV009 treatment during Part A, will receive BIVV009 (based on weight) biweekly for up to 52 weeks of BIVV009 after Last Patient In (LPI) in part B.
intervention type: Drug
intervention name: BIVV009 6.5 grams
description: Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009.
arm group label: BIVV009
intervention type: Drug
intervention name: BIVV009 7.5 grams
description: Participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009.
arm group label: BIVV009
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: United Kingdom
country: United States
citation: Broome CM, Roth A, Kuter DJ, Scully M, Smith R, Wang J, Reuter C, Hobbs W, Daak A. Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia. Blood Adv. 2023 Mar 28;7(6):987-996. doi: 10.1182/bloodadvances.2021006864.
PMID: 35973190
responsible party type: Sponsor
mesh term: Thrombocytopenia
mesh term: Purpura
mesh term: Purpura, Thrombocytopenic, Idiopathic
mesh term: Purpura, Thrombocytopenic
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org