Extended Half Life Factor (EHF) Products For Heavy Menstrual Bleeding in Hemophilia Carriers

NCT ID: NCT03272568

Last Updated: 2020-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-14
• Study Completion Date: 2019-12-31

Brief 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.

Conditions

Hemophilia; Menstrual Flow Excessive

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hemophilia A symptomatic female carriers

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.

Group Type: EXPERIMENTAL

Recombinant FVIII Fc fusion product Eloctate

Intervention Type: DRUG

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).

Patient-operated diagnostic device for anemia AnemoCheck.

Intervention Type: DEVICE

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.

Hemophilia B symptomatic female carriers

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.

Group Type: EXPERIMENTAL

Recombinant FIX Fc fusion product Alprolix

Intervention Type: DRUG

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).

Patient-operated diagnostic device for anemia AnemoCheck.

Intervention Type: DEVICE

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.

Interventions

Recombinant FVIII Fc fusion product Eloctate

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).

Intervention Type: DRUG

Recombinant FIX Fc fusion product Alprolix

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).

Intervention Type: DRUG

Patient-operated diagnostic device for anemia AnemoCheck.

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.

Intervention Type: DEVICE

Other Intervention Names

Eloctate; Alprolix; AnemoCheck

Eligibility Criteria

Inclusion Criteria

• Females of reproductive age who experience monthly menstrual bleedings
• Female Hemophilia A or B carrier (heterozygote, lyonized or Turner's Syndrome)
• FVIII or FIX activity ≤60% at time of the study
• Baseline Pictorial Bleeding Assessment Chart >150 mean at time of recruitment
• Negative pregnancy test at time of enrollment
• Both female and her male partner have agreed to use an acceptable barrier method of birth control (e.g., diaphragm, cervical cap, male condom, female condom, and spermicidal foam, sponges, and film) throughout the duration of this study (for sexually active participants)

Exclusion Criteria

• Has not reached menarche
• Menopause: natural or induced by surgical/medical treatment
• Pregnant or breasfeeding
• Female or her male partner refuses to use barrier method of birth control (for sexually active)
• Current use of any of the following contraceptives (copper IUD, oral combined, Progestin-only including but not limited to: Provera, Aygestin, Nexplanon, Implanon, Depo Provera, Mirena IUD)
• VWF:Ag or VWF:RCo <40%
• Diagnosis of a qualitative platelet disorder
• Personal history of thrombosis or superficial thrombosis
• First degree relative with a history of thrombosis
• Personal history of concomitant bleeding or clotting disorder
• Cigarette smoker
• Willing to avoid taking an anti-fibrinolytic agent (amicar, transexamic acid, lysteda) during the trial

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bioverativ Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Robert Sidonio

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Sidonio, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Clinical Research Network

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00095067

Identifier Type: -

Identifier Source: org_study_id