Extended Half Life Factor (EHF) Products For Heavy Menstrual Bleeding in Hemophilia Carriers
Condition: Hemophilia; Menstrual Flow Excessive
MeSH terms: Menorrhagia; Hemophilia A
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Recombinant FVIII Fc fusion product Eloctate; Recombinant FIX Fc fusion product Alprolix; Patient-operated diagnostic device for anemia AnemoCheck.
Intervention type(s): Drug; Drug; Device
Intervention description(s): 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).; 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).; 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.
Other intervention name(s): Eloctate; Alprolix; AnemoCheck
Intervention MeSH terms: Immunoglobulin Fc Fragments
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.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Extended Life Plasma Derived Factor Products; Female hemophilia A and B carriers; Menorrhagia