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

NCT03272568 | Completed Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: IRB00095067
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophilia; Menstrual Flow Excessive

Keywords

Extended Life Plasma Derived Factor Products; Female hemophilia A and B carriers; Menorrhagia

Outcome Measures

Primary Outcomes (1)

• Reduction in menstrual bleeding measured by the Pictorial Bleeding Assessment Chart (PBAC).

  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.

  Monthly throughout study duration for 7 months

Secondary Outcomes (7)

• Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS-43) score.

  Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months.

• Change in Short Form 36 (SF-36) score.

  Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months

• Change in Menorrhagia Impact Questionnaire (MIQ) score.

  Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months

• Number of hypersensitivity reactions.

  Througout the interventional phase of the study (visit 4-7 of the study or months 4-7)

• Accuracy of hemoglobin levels detection by Anemocheck.

  Every other day during 2 consecutive menstrual cycles during non-interventional study phase (up to Day 60 of the study).

Study Arms (2)

Hemophilia A symptomatic female carriers

EXPERIMENTAL

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.

Drug: Recombinant FVIII Fc fusion product Eloctate; Device: Patient-operated diagnostic device for anemia AnemoCheck.

Hemophilia B symptomatic female carriers

EXPERIMENTAL

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.

Drug: Recombinant FIX Fc fusion product Alprolix; Device: Patient-operated diagnostic device for anemia AnemoCheck.

Interventions

Recombinant FVIII Fc fusion product Eloctate 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).

Also known as: Eloctate

Hemophilia A symptomatic female carriers

Recombinant FIX Fc fusion product Alprolix 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).

Also known as: Alprolix

Hemophilia B symptomatic female carriers

Patient-operated diagnostic device for anemia AnemoCheck. 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.

Also known as: AnemoCheck

Hemophilia A symptomatic female carriers; Hemophilia B symptomatic female carriers

Eligibility Criteria

• Age: 14 Years - 55 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Bioverativ Therapeutics Inc.: collaborator

Study Sites (1)

Emory University Hospital Clinical Research Network

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Hemophilia A; Menorrhagia

Interventions

factor VIII-Fc fusion protein; factor IX Fc fusion protein

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances

Study Officials

• Robert Sidonio, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 5, 2017
• Study Start: February 14, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: May 18, 2020

Record last verified: 2020-05

Locations

US (1)