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

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.

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