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

Brief Title

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

Official Title

A Feasibility Trial Using Extended Half Life Factor Products in the Reduction of Menstrual Bleeding in Symptomatic Hemophilia A and B Carriers

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.

Study Phase

Early Phase 1

Study Type

Interventional

Primary Outcome

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

Secondary Outcome

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

Condition

Hemophilia

Intervention

Recombinant FVIII Fc fusion product Eloctate

Study Arms / Comparison Groups

 Hemophilia A symptomatic female carriers

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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

February 14, 2018

Completion Date

December 31, 2019

Primary Completion Date

December 31, 2019

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

Gender

Female

Ages

14 Years - 55 Years

Accepts Healthy Volunteers

No

Contacts

Robert Sidonio, MD, MSc, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT03272568

Organization ID

IRB00095067

Responsible Party

Principal Investigator

Study Sponsor

Emory University

Collaborators

 Bioverativ Therapeutics Inc.

Study Sponsor

Robert Sidonio, MD, MSc, Principal Investigator, Emory University

Verification Date

May 2020