Prevention of Bleeding in Patients With Moderate and Severe Hemophilia A Playing Sports: A Comparison Between Factor VIII and Emicizumab Prophylaxis

Brief Title

Prevention of Bleeding in Patients With Moderate and Severe Hemophilia A Playing Sports: A Comparison Between Factor VIII and Emicizumab Prophylaxis

Official Title

Prevention of Bleeding in Patients With Moderate and Severe Hemophilia A Playing Sports: A Comparison Between Factor VIII and Emicizumab Prophylaxis -STEP: SporTs Emicizumab Prophylaxis

Brief Summary

Hemophilia A (HA) is a genetic bleeding disorder resulting from a deficiency or absence of
factor VIII (FVIII), which is necessary in the clotting process. This disorder occurs mostly
in males and in severe cases causes frequent bleeding episodes in joints and muscles which
can lead to progressive damage that affects mobility and quality of life. Prophylactic FVIII
administered intravenously every other day has been the standard of care treatment for HA for
the past few decades.

Sports and physical activity are generally encouraged in patients with hemophilia on
appropriate prophylactic treatment to increase strength, prevent or decrease obesity, accrue
and maintain bone density and encourage normal socialization. To ensure safety with
participation in sports in persons with hemophilia A (PWHA), timing of FVIII administration
is often adjusted to maximize FVIII at the time of sports. The exact factor level that is
needed to safely participate in sports and minimize bleeding risk is not yet known. Based on
clinical practice, infusion of FVIII to near the lower limit of normal right before
participation in sports generally works to prevent bleeding.

The study is looking at how well the newly approved medication Emicizumab works compared to
Factor VIII to prevent bleeding in patients with Hemophilia A who play sports. The study will
enroll children and adolescents who are already on Emicizumab or Factor VIII who are
currently playing sports.

Detailed Description

      Hemophilia A (HA) is a genetic bleeding disorder resulting from a deficiency or absence of
      factor VIII (FVIII) which is necessary in the clotting process. This disorder occurs mostly
      in males and in severe cases causes frequent bleeding episodes in joints and muscles which
      can lead to progressive damage that affects mobility and quality of life. Intravenous
      prophylactic (preventative) treatment is the standard of care used in minimizing bleeding
      events and complications. Since the 1990s recombinant FVIII (rFVIII) concentrates have been
      standard of care treatment options for patients with hemophilia A. Prophylactic treatment is
      burdensome because it requires self-administered intravenous infusions several (3-4) times a
      week and prophylactic FVIII does not completely prevent bleeding.

      Sports and physical activity are generally encouraged in patients with hemophilia on
      appropriate prophylactic treatment to increase strength, prevent or decrease obesity, accrue
      and maintain bone density and encourage normal socialization. To ensure safety with
      participation in sports in persons with hemophilia A (PWHA), timing of FVIII administration
      is frequently adjusted to maximize FVIII at the time of sports. The exact factor level that
      is needed to safely participate in sports and minimize bleeding risk is not yet known. Based
      on clinical practice, infusion of FVIII to near the lower limit of normal right before
      participation in sports generally works to prevent bleeding.

      Emicizumab is an engineered antibody that mimics what activated factor VIII does in the blood
      to help it clot. Emicizumab is an antibody and is present in the blood for a long time and
      approximately 50% of an injected dose is still circulating in the blood 4 weeks later; this
      permits less frequent dosing (Anywhere from once a week to once every 4 weeks). Emicizumab
      can be injected under the skin (subcutaneous) instead of having to be injected into a vein
      (intravenous). Emicizumab's convenience compared to FVIII, reduced bleeding rate, and in many
      cases decreased annual cost, have led to its adoption by many patients with HA. Emicizumab
      does not completely normalize hemostasis (the physiological process that stops bleeding) and
      although the exact comparison of hemostatic correction on maintenance doses of Emicizumab to
      that with FVIII replacement cannot be determined with existing assays, it has been clinically
      demonstrated that Emicizumab changes the bleeding characteristics of a patient with severe
      hemophilia A to a milder profile. While this may provide sufficient protection to prevent
      spontaneous bleeding into the joints, it remains unknown if this is sufficient to prevent
      activity/sports related joint bleeds (especially activities with moderate to high risk of
      bleeding).

      A disadvantage of Emicizumab prophylaxis is that the steady state produced with Emicizumab
      prophylaxis does not allow dosing at the time of sports participation. One major question is
      whether the "steady state" levels of hemostasis achieved with Emicizumab are enough to
      prevent joint damage with sports participation, and whether there is a threshold of
      participant age or size or activity intensity above which Emicizumab is not generally
      adequate.

      Emicizumab use permits maintenance of "steady state" hemostasis in the range of mild
      hemophilia without frequent infusions. Studying patients taking Emicizumab while engaging in
      sports permits us to study the effects of participation in physical activity with steady
      state hemostasis levels in the range of mild hemophilia compared to peak hemostatic levels
      from factor infusions given immediately before engaging in activity/sports. This is a crucial
      factor in the decision-making process for physicians making treatment recommendations to
      optimize preventive therapy for physically active people with hemophilia A.

      The purpose of this investigator-initiated study is to better understand the safety of sports
      in people with Hemophilia A, the breakthrough bleed rates, and the types of bleeds related to
      sports activities in patients on Emicizumab vs traditional FVIII prophylaxis. This
      information will help in the decision-making process for physicians making treatment
      recommendations for physically active people with hemophilia A.

Study Type

Observational

Primary Outcome

Number of bleeds

Secondary Outcome

 Change in HJHS scores

Condition

Hemophilia A

Intervention

Emicizumab

Study Arms / Comparison Groups

 Emicizumab Prophylaxis

Description:  This group will include patients on standard of care Emicizumab prophylaxis for Hemophilia A

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

May 2022

Completion Date

January 2027

Primary Completion Date

December 2026

Eligibility Criteria

        Inclusion Criteria:

          1. Participant (if 18 years of age or older) or parent/LAR is willing and able to provide
             written informed consent; minor participant is willing and able to provide assent, if
             applicable based on site and local regulations

          2. Male participants with moderate to severe Hemophilia A ( FVIII activity

Gender

Male

Ages

6 Years - 18 Years

Contacts

Meera Chitlur, MD, 313-577-7500, [email protected]

Administrative Informations

NCT ID

NCT05022459

Organization ID

STEP Study

Responsible Party

Principal Investigator

Study Sponsor

Wayne State University

Collaborators

 Genentech, Inc.

Study Sponsor

Meera Chitlur, MD, Principal Investigator, Wayne State University

Verification Date

March 2022