<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/NCT03272568</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00095067</org_study_id>
    <nct_id>NCT03272568</nct_id>
  </id_info>
  <brief_title>Extended Half Life Factor (EHF) Products For Heavy Menstrual Bleeding in Hemophilia Carriers</brief_title>
  <official_title>A Feasibility Trial Using Extended Half Life Factor Products in the Reduction of Menstrual Bleeding in Symptomatic Hemophilia A and B Carriers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bioverativ Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this feasibility study is to find out if two clotting factor products,&#xD;
      Eloctate [hemophilia A] and Alprolix [hemophilia B], can reduce the amount of menstrual&#xD;
      bleeding in female hemophilia A and B carriers (14 years of age or older) who have severe or&#xD;
      heavy bleeding. These products are FDA-approved for use in males with hemophilia A and B to&#xD;
      prevent and treat bleeding. They are not approved specifically to reduce menstrual bleeding,&#xD;
      but may be useful for this purpose. Both products have an &quot;extended half life&quot; which means&#xD;
      they circulate in the body longer than other FVIII or FIX products. The study team will&#xD;
      gather additional information about the safety of these drugs and how well they work. The&#xD;
      results of this feasibility study will provide information for an upcoming larger study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hemophilia A or B is caused by defects in the factor VIII or IX gene, respectively, of which&#xD;
      is located on the X chromosome. This disorder exhibits X-linked inheritance, in which&#xD;
      primarily males, with a single X chromosome, are affected and females, with two X&#xD;
      chromosomes, are heterozygotes, or carriers. Hemophilia carriers show a wide distribution of&#xD;
      factor VIII or IX levels with a mean of 50%, which overlaps the distribution of non-carrier&#xD;
      women.&#xD;
&#xD;
      Heavy menstrual bleeding is defined as menstrual bleeding that lasts more than 7 days or more&#xD;
      specifically as the loss of more than 80cc of blood per cycle. Management is critical as it&#xD;
      can lead to iron deficiency anemia, lead to school absence and affects the general quality of&#xD;
      life. There are multiple options to control or reduce menstrual bleeding in hemophilia A and&#xD;
      B carriers, they include but not limited to the following options: Antifibrinolytics&#xD;
      (Aminocaproic acid, Tranexamic acid), Synthetic desmopressin (DDAVP, SQ or IN) or hormonal&#xD;
      therapies (Combined oral contraceptives, Progestin only options, IUD, etc).&#xD;
&#xD;
      The use of recombinant factor replacement has been poorly studied and limited by a relatively&#xD;
      short half-life in relation to the typical length of a menstrual period. The purpose of this&#xD;
      feasibility study is to find out if two clotting factor products, Eloctate [hemophilia A] and&#xD;
      Alprolix [hemophilia B], can reduce the amount of menstrual bleeding in female hemophilia A&#xD;
      and B carriers (14 years of age or older) who have severe or heavy bleeding. These products&#xD;
      are FDA-approved for use in males with hemophilia A and B to prevent and treat bleeding. They&#xD;
      are not approved specifically to reduce menstrual bleeding, but may be useful for this&#xD;
      purpose. Both products have an &quot;extended half life&quot; which means they circulate in the body&#xD;
      longer than other FVIII or FIX products. The study team will gather additional information&#xD;
      about the safety of these drugs and how well they work. Five out of the 16 anticipated&#xD;
      enrolled patients will be approach to request participation in the exploratory aim in which&#xD;
      the subject is taught to perform a hemoglobin check (CBC) every other day using a novel point&#xD;
      of care device (Anemocheck) during 2 consecutive menstrual cycles. In addition, they will&#xD;
      have CBCs drawn within 4-6 hours for comparison and correlation. The study team will also&#xD;
      correlate symptoms of heavy menstrual bleeding with a 2grams drop in the hemoglobin. All the&#xD;
      results of this study will provide information for an upcoming larger study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 14, 2018</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">December 31, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>During interventional portion of the study, participants will be infused with either Eloctate (hemophilia A carriers) or Alprolix (hemophilia B carriers) to maintain FVIII or FIX &gt;48hours. Five out of the 16 enrolled patients will self-perform a hemoglobin check every other day using a novel device Anemocheck during 2 consecutive menstrual cycles.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction in menstrual bleeding measured by the Pictorial Bleeding Assessment Chart (PBAC).</measure>
    <time_frame>Monthly throughout study duration for 7 months</time_frame>
    <description>Menstrual loss is tracked via paper and electronic PBAC, calculated via visual interpretation centrally and correlated to the ability of a participant to correctly assign pad or tampon saturation. The PBAC will be estimated (mean) over the three-month intervention period to assess if 30% reduction in menstrual bleeding was achieved. PBAC is a semi-quantitative, self-administered pictorial tool. The total score is calculated by adding up the sum of all scores for the tampons or pads used, with a score greater than 150 having an 86% sensitivity and 89% specificity for heavy menstrual bleeding (HMB). Possible range is dependent on quantitative and qualitative amount of bleeding during menstruation:&#xD;
For tampons: 0.5-1 for lightly stained, 1-4 for moderately soiled and 4-12 for completely saturated tampons.&#xD;
For pads: 1 for lightly stained, 2-6 for moderately soiled and 4-15 for completely saturated pads.&#xD;
Clots were given a score of 1 for small and 5 for large clots.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS-43) score.</measure>
    <time_frame>Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months.</time_frame>
    <description>To determine whether the use of the study drugs leads to a significant improvement in Quality of Life (QOL) the study establishes a baseline QOL and measures change monthly and 6-month change. The PROMIS 43 profile is a QOL assessment tool of 43 questions from 9 health domains and 10 questions focused on sexual health. The PROMIS assesses patient reported outcomes in three major categories: physical health, mental health, and social health. Each item has five response options except for the Pain Intensity item which has eleven options.A raw score is created from each short form. To find the total raw score the values of the response to each question are summed up within each domain. The applicable score conversion table translates the total raw score into standardized T-score that is reported as the final score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Short Form 36 (SF-36) score.</measure>
    <time_frame>Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months</time_frame>
    <description>To determine whether the study treatment leads to a clinically significant improvement in Quality of Life (QOL) the study team establishes a baseline quality of life and measures change monthly as well as 6-month change in SF-36. SF-36 is a a 36-item patient reported survey of health consisting of 8 scaled scores with a lower score indicating disability in the one of the 8 sections or domains.The scoring system for the SF-36 is relatively complex and generates subscale scores for physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role-limitations due to emotional problems, and mental health. Two summary scores can also be derived from the SF-36: the physical component summary and the mental component summary.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Menorrhagia Impact Questionnaire (MIQ) score.</measure>
    <time_frame>Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months</time_frame>
    <description>The MIQ consists of six individual measures or items. The first 4 items are evaluated by using 4-point (item 1) or 5-point (items 2-4) response scales. No summative scale is derived for item 5 as it serves as a descriptive tool to characterize limitations of specific activities and is viewed as supporting information for items 2-4. Item 6 represents a global assessment (impact, degree, and meaningfulness) of the change in menstrual bleeding lost (MBL) when compared to the previous period. Impact response options included a 0 ('almost the same'), 1 ('better'), or 2 ('worse'). If a change is reported, then a 7-point rating scale is used to specify the degree of improvement (item 6a) or worsening (item 6b). Finally, item 6c (meaningfulness of change in MBL) provides an overall assessment of the subjective perception of the change in MBL and may be considered an important component of the MIQ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hypersensitivity reactions.</measure>
    <time_frame>Througout the interventional phase of the study (visit 4-7 of the study or months 4-7)</time_frame>
    <description>Since Eloctate and Alprolix are biological products, hypersensitivity reactions, including anaphylaxis and anaphylactic reactions, may occur. Nurses and patients will be trained to recognize the signs and symptoms associated with potential hypersensitivity, anaphylactic, and anaphylactoid reactions, and instructed to provide/seek immediate care. Patients/caregivers will receive two alert cards with this information and instructions. For patients with a previous history of a clinically significant hypersensitivity reaction, the site will call the patient 24 hours after each dose to assess the status of the patient. Additional precautions following each of these doses may also be considered including having an extended observation period or IV access prior to dosing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accuracy of hemoglobin levels detection by Anemocheck.</measure>
    <time_frame>Every other day during 2 consecutive menstrual cycles during non-interventional study phase (up to Day 60 of the study).</time_frame>
    <description>Exploratory arm participants will self-perform hemoglobin check using Anemocheck every other day during 2 consecutive menstrual cycles. To determine the feasibility and utility of Anemocheck in the monitoring of hemoglobin during a menstruation, the study team will assess correlation of symptoms of heavy menstrual bleeding with a 2g drop in the hemoglobin detected by Anemocheck, and correlation of hemoglobin level obtained by local Lab (within 4-6 hours).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in FVIII level after the first dose of Eloctate.</measure>
    <time_frame>First visit of interventional study phase (visit 4, day 90 of the study) : 15-30 min, 2 hours, 4 hours, 18-24 hour after infusion.</time_frame>
    <description>An assessment of FVIII level via blood draw will be performed after the first dose of the drug at four time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in FIX level after the first dose of Alpolix.</measure>
    <time_frame>First visit of interventional study phase (visit 4, day 90 of the study) : 15-30 min,4 hours,48 hours, and 72 hours after infusion.</time_frame>
    <description>An assessment of FIX level via blood draw will be performed after the first dose of the drug at four time points.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Hemophilia</condition>
  <condition>Menstrual Flow Excessive</condition>
  <arm_group>
    <arm_group_label>Hemophilia A symptomatic female carriers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hemophilia A symptomatic female carriers with a baseline FVIII activity of ≤60% receive recombinant FVIII Fc fusion product Eloctate.&#xD;
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hemophilia B symptomatic female carriers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hemophilia B symptomatic female carriers with a baseline FIX activity of ≤60% receive recombinant FIX Fc fusion product Alprolix.&#xD;
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant FVIII Fc fusion product Eloctate</intervention_name>
    <description>Subjects will get FVIII activity corrected from the baseline level to 100-150% with Eloctate on the first day of menstruation at the beginning of the study interventional phase. The first dose of the drug will be given in the clinics via slow injection into a vein (infusion). A short assessment of pharmacokinetics (PK) (4 time-points blood draw: 15 min, 2 hours, 4 hours, 20 hours after the infusion) will be performed to assist with subsequent dosing. 2 total doses of Eloctate likely to be given on day 1 and 3 of menstrual period. The subject will then receive three additional PK-adjusted monthly doses of Eloctate (with no less than 21 days interval).</description>
    <arm_group_label>Hemophilia A symptomatic female carriers</arm_group_label>
    <other_name>Eloctate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant FIX Fc fusion product Alprolix</intervention_name>
    <description>Subjects will get FIX activity corrected from the baseline level to 100-150% with Alprolix on the first day of menstruation at the beginning of the study interventional phase. The first dose of the drug will be given in the clinics via slow injection into a vein (infusion). A short assessment of pharmacokinetics (PK) (4 time-points blood draw: 15 min, 4 hours, 48 hours, 72 hours after the infusion) will be performed (by home nursing or local lab) to assist with subsequent dosing. Single dose of Alprolix likely to be given on day 1 of menstrual period. The subject will then receive three additional PK-adjusted monthly doses of Alprolix (with no less than 21 days interval).</description>
    <arm_group_label>Hemophilia B symptomatic female carriers</arm_group_label>
    <other_name>Alprolix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Patient-operated diagnostic device for anemia AnemoCheck.</intervention_name>
    <description>Each AnemoCheck test kit enables patients to check hemoglobin levels by pricking their finger to draw 5 μL of blood into a capillary tube, inserting that tube into a larger tube with a pre-filled chemical solution, mixing, waiting one minute, and assessing the color change of the solution using a reference color scale card included with the kit. The test is able to subjectively differentiate low, medium and high levels of hemoglobin to diagnose anemia at home. Study participants are taught to perform a hemoglobin check every other day using Anemocheck during 2 consecutive menstrual cycles. In addition they will have hemoglobin level obtained locally (LabCorp) drawn within 4-6 hours for comparison and correlation.</description>
    <arm_group_label>Hemophilia A symptomatic female carriers</arm_group_label>
    <arm_group_label>Hemophilia B symptomatic female carriers</arm_group_label>
    <other_name>AnemoCheck</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females of reproductive age who experience monthly menstrual bleedings&#xD;
&#xD;
          -  Female Hemophilia A or B carrier (heterozygote, lyonized or Turner's Syndrome)&#xD;
&#xD;
          -  FVIII or FIX activity ≤60% at time of the study&#xD;
&#xD;
          -  Baseline Pictorial Bleeding Assessment Chart &gt;150 mean at time of recruitment&#xD;
&#xD;
          -  Negative pregnancy test at time of enrollment&#xD;
&#xD;
          -  Both female and her male partner have agreed to use an acceptable barrier method of&#xD;
             birth control (e.g., diaphragm, cervical cap, male condom, female condom, and&#xD;
             spermicidal foam, sponges, and film) throughout the duration of this study (for&#xD;
             sexually active participants)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has not reached menarche&#xD;
&#xD;
          -  Menopause: natural or induced by surgical/medical treatment&#xD;
&#xD;
          -  Pregnant or breasfeeding&#xD;
&#xD;
          -  Female or her male partner refuses to use barrier method of birth control (for&#xD;
             sexually active)&#xD;
&#xD;
          -  Current use of any of the following contraceptives (copper IUD, oral combined,&#xD;
             Progestin-only including but not limited to: Provera, Aygestin, Nexplanon, Implanon,&#xD;
             Depo Provera, Mirena IUD)&#xD;
&#xD;
          -  VWF:Ag or VWF:RCo &lt;40%&#xD;
&#xD;
          -  Diagnosis of a qualitative platelet disorder&#xD;
&#xD;
          -  Personal history of thrombosis or superficial thrombosis&#xD;
&#xD;
          -  First degree relative with a history of thrombosis&#xD;
&#xD;
          -  Personal history of concomitant bleeding or clotting disorder&#xD;
&#xD;
          -  Cigarette smoker&#xD;
&#xD;
          -  Willing to avoid taking an anti-fibrinolytic agent (amicar, transexamic acid, lysteda)&#xD;
             during the trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female</gender_description>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert Sidonio, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University Hospital Clinical Research Network</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>May 15, 2020</last_update_submitted>
  <last_update_submitted_qc>May 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Robert Sidonio</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Extended Life Plasma Derived Factor Products</keyword>
  <keyword>Female hemophilia A and B carriers</keyword>
  <keyword>Menorrhagia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Menorrhagia</mesh_term>
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulin Fc Fragments</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03272568
org study id: IRB00095067
nct id: NCT03272568
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
The purpose of this feasibility study is to find out if two clotting factor products,
      Eloctate [hemophilia A] and Alprolix [hemophilia B], can reduce the amount of menstrual
      bleeding in female hemophilia A and B carriers (14 years of age or older) who have severe or
      heavy bleeding. These products are FDA-approved for use in males with hemophilia A and B to
      prevent and treat bleeding. They are not approved specifically to reduce menstrual bleeding,
      but may be useful for this purpose. Both products have an "extended half life" which means
      they circulate in the body longer than other FVIII or FIX products. The study team will
      gather additional information about the safety of these drugs and how well they work. The
      results of this feasibility study will provide information for an upcoming larger study.
Hemophilia A or B is caused by defects in the factor VIII or IX gene, respectively, of which
      is located on the X chromosome. This disorder exhibits X-linked inheritance, in which
      primarily males, with a single X chromosome, are affected and females, with two X
      chromosomes, are heterozygotes, or carriers. Hemophilia carriers show a wide distribution of
      factor VIII or IX levels with a mean of 50%, which overlaps the distribution of non-carrier
      women.

      Heavy menstrual bleeding is defined as menstrual bleeding that lasts more than 7 days or more
      specifically as the loss of more than 80cc of blood per cycle. Management is critical as it
      can lead to iron deficiency anemia, lead to school absence and affects the general quality of
      life. There are multiple options to control or reduce menstrual bleeding in hemophilia A and
      B carriers, they include but not limited to the following options: Antifibrinolytics
      (Aminocaproic acid, Tranexamic acid), Synthetic desmopressin (DDAVP, SQ or IN) or hormonal
      therapies (Combined oral contraceptives, Progestin only options, IUD, etc).

      The use of recombinant factor replacement has been poorly studied and limited by a relatively
      short half-life in relation to the typical length of a menstrual period. The purpose of this
      feasibility study is to find out if two clotting factor products, Eloctate [hemophilia A] and
      Alprolix [hemophilia B], can reduce the amount of menstrual bleeding in female hemophilia A
      and B carriers (14 years of age or older) who have severe or heavy bleeding. These products
      are FDA-approved for use in males with hemophilia A and B to prevent and treat bleeding. They
      are not approved specifically to reduce menstrual bleeding, but may be useful for this
      purpose. Both products have an "extended half life" which means they circulate in the body
      longer than other FVIII or FIX products. The study team will gather additional information
      about the safety of these drugs and how well they work. Five out of the 16 anticipated
      enrolled patients will be approach to request participation in the exploratory aim in which
      the subject is taught to perform a hemoglobin check (CBC) every other day using a novel point
      of care device (Anemocheck) during 2 consecutive menstrual cycles. In addition, they will
      have CBCs drawn within 4-6 hours for comparison and correlation. The study team will also
      correlate symptoms of heavy menstrual bleeding with a 2grams drop in the hemoglobin. All the
      results of this study will provide information for an upcoming larger study.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: During interventional portion of the study, participants will be infused with either Eloctate (hemophilia A carriers) or Alprolix (hemophilia B carriers) to maintain FVIII or FIX >48hours. Five out of the 16 enrolled patients will self-perform a hemoglobin check every other day using a novel device Anemocheck during 2 consecutive menstrual cycles.
primary purpose: Treatment
masking: None (Open Label)
measure: Reduction in menstrual bleeding measured by the Pictorial Bleeding Assessment Chart (PBAC).
time frame: Monthly throughout study duration for 7 months
description: Menstrual loss is tracked via paper and electronic PBAC, calculated via visual interpretation centrally and correlated to the ability of a participant to correctly assign pad or tampon saturation. The PBAC will be estimated (mean) over the three-month intervention period to assess if 30% reduction in menstrual bleeding was achieved. PBAC is a semi-quantitative, self-administered pictorial tool. The total score is calculated by adding up the sum of all scores for the tampons or pads used, with a score greater than 150 having an 86% sensitivity and 89% specificity for heavy menstrual bleeding (HMB). Possible range is dependent on quantitative and qualitative amount of bleeding during menstruation:
For tampons: 0.5-1 for lightly stained, 1-4 for moderately soiled and 4-12 for completely saturated tampons.
For pads: 1 for lightly stained, 2-6 for moderately soiled and 4-15 for completely saturated pads.
Clots were given a score of 1 for small and 5 for large clots.
measure: Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS-43) score.
time frame: Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months.
description: To determine whether the use of the study drugs leads to a significant improvement in Quality of Life (QOL) the study establishes a baseline QOL and measures change monthly and 6-month change. The PROMIS 43 profile is a QOL assessment tool of 43 questions from 9 health domains and 10 questions focused on sexual health. The PROMIS assesses patient reported outcomes in three major categories: physical health, mental health, and social health. Each item has five response options except for the Pain Intensity item which has eleven options.A raw score is created from each short form. To find the total raw score the values of the response to each question are summed up within each domain. The applicable score conversion table translates the total raw score into standardized T-score that is reported as the final score.
measure: Change in Short Form 36 (SF-36) score.
time frame: Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months
description: To determine whether the study treatment leads to a clinically significant improvement in Quality of Life (QOL) the study team establishes a baseline quality of life and measures change monthly as well as 6-month change in SF-36. SF-36 is a a 36-item patient reported survey of health consisting of 8 scaled scores with a lower score indicating disability in the one of the 8 sections or domains.The scoring system for the SF-36 is relatively complex and generates subscale scores for physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role-limitations due to emotional problems, and mental health. Two summary scores can also be derived from the SF-36: the physical component summary and the mental component summary.
measure: Change in Menorrhagia Impact Questionnaire (MIQ) score.
time frame: Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months
description: The MIQ consists of six individual measures or items. The first 4 items are evaluated by using 4-point (item 1) or 5-point (items 2-4) response scales. No summative scale is derived for item 5 as it serves as a descriptive tool to characterize limitations of specific activities and is viewed as supporting information for items 2-4. Item 6 represents a global assessment (impact, degree, and meaningfulness) of the change in menstrual bleeding lost (MBL) when compared to the previous period. Impact response options included a 0 ('almost the same'), 1 ('better'), or 2 ('worse'). If a change is reported, then a 7-point rating scale is used to specify the degree of improvement (item 6a) or worsening (item 6b). Finally, item 6c (meaningfulness of change in MBL) provides an overall assessment of the subjective perception of the change in MBL and may be considered an important component of the MIQ.
measure: Number of hypersensitivity reactions.
time frame: Througout the interventional phase of the study (visit 4-7 of the study or months 4-7)
description: Since Eloctate and Alprolix are biological products, hypersensitivity reactions, including anaphylaxis and anaphylactic reactions, may occur. Nurses and patients will be trained to recognize the signs and symptoms associated with potential hypersensitivity, anaphylactic, and anaphylactoid reactions, and instructed to provide/seek immediate care. Patients/caregivers will receive two alert cards with this information and instructions. For patients with a previous history of a clinically significant hypersensitivity reaction, the site will call the patient 24 hours after each dose to assess the status of the patient. Additional precautions following each of these doses may also be considered including having an extended observation period or IV access prior to dosing.
measure: Accuracy of hemoglobin levels detection by Anemocheck.
time frame: Every other day during 2 consecutive menstrual cycles during non-interventional study phase (up to Day 60 of the study).
description: Exploratory arm participants will self-perform hemoglobin check using Anemocheck every other day during 2 consecutive menstrual cycles. To determine the feasibility and utility of Anemocheck in the monitoring of hemoglobin during a menstruation, the study team will assess correlation of symptoms of heavy menstrual bleeding with a 2g drop in the hemoglobin detected by Anemocheck, and correlation of hemoglobin level obtained by local Lab (within 4-6 hours).
measure: Change in FVIII level after the first dose of Eloctate.
time frame: First visit of interventional study phase (visit 4, day 90 of the study) : 15-30 min, 2 hours, 4 hours, 18-24 hour after infusion.
description: An assessment of FVIII level via blood draw will be performed after the first dose of the drug at four time points.
measure: Change in FIX level after the first dose of Alpolix.
time frame: First visit of interventional study phase (visit 4, day 90 of the study) : 15-30 min,4 hours,48 hours, and 72 hours after infusion.
description: An assessment of FIX level via blood draw will be performed after the first dose of the drug at four time points.
arm group label: Hemophilia A symptomatic female carriers
arm group type: Experimental
description: Hemophilia A symptomatic female carriers with a baseline FVIII activity of ≤60% receive recombinant FVIII Fc fusion product Eloctate.
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.
arm group label: Hemophilia B symptomatic female carriers
arm group type: Experimental
description: Hemophilia B symptomatic female carriers with a baseline FIX activity of ≤60% receive recombinant FIX Fc fusion product Alprolix.
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.
intervention type: Drug
intervention name: Recombinant FVIII Fc fusion product Eloctate
description: Subjects will get FVIII activity corrected from the baseline level to 100-150% with Eloctate on the first day of menstruation at the beginning of the study interventional phase. The first dose of the drug will be given in the clinics via slow injection into a vein (infusion). A short assessment of pharmacokinetics (PK) (4 time-points blood draw: 15 min, 2 hours, 4 hours, 20 hours after the infusion) will be performed to assist with subsequent dosing. 2 total doses of Eloctate likely to be given on day 1 and 3 of menstrual period. The subject will then receive three additional PK-adjusted monthly doses of Eloctate (with no less than 21 days interval).
arm group label: Hemophilia A symptomatic female carriers
other name: Eloctate
intervention type: Drug
intervention name: Recombinant FIX Fc fusion product Alprolix
description: Subjects will get FIX activity corrected from the baseline level to 100-150% with Alprolix on the first day of menstruation at the beginning of the study interventional phase. The first dose of the drug will be given in the clinics via slow injection into a vein (infusion). A short assessment of pharmacokinetics (PK) (4 time-points blood draw: 15 min, 4 hours, 48 hours, 72 hours after the infusion) will be performed (by home nursing or local lab) to assist with subsequent dosing. Single dose of Alprolix likely to be given on day 1 of menstrual period. The subject will then receive three additional PK-adjusted monthly doses of Alprolix (with no less than 21 days interval).
arm group label: Hemophilia B symptomatic female carriers
other name: Alprolix
intervention type: Device
intervention name: Patient-operated diagnostic device for anemia AnemoCheck.
description: Each AnemoCheck test kit enables patients to check hemoglobin levels by pricking their finger to draw 5 μL of blood into a capillary tube, inserting that tube into a larger tube with a pre-filled chemical solution, mixing, waiting one minute, and assessing the color change of the solution using a reference color scale card included with the kit. The test is able to subjectively differentiate low, medium and high levels of hemoglobin to diagnose anemia at home. Study participants are taught to perform a hemoglobin check every other day using Anemocheck during 2 consecutive menstrual cycles. In addition they will have hemoglobin level obtained locally (LabCorp) drawn within 4-6 hours for comparison and correlation.
arm group label: Hemophilia A symptomatic female carriers
arm group label: Hemophilia B symptomatic female carriers
other name: AnemoCheck
criteria: 
gender: Female
gender based: Yes
gender description: Female
minimum age: 14 Years
maximum age: 55 Years
healthy volunteers: No
last name: Robert Sidonio, MD, MSc
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Robert Sidonio
investigator title: Assistant Professor of Pediatrics
mesh term: Menorrhagia
mesh term: Hemophilia A
mesh term: Immunoglobulin Fc Fragments
sharing ipd: Undecided