Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors

Study Overview
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Brief Summary
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Study B7841007 is an open-label extension study to assess the long-term safety, tolerability, and efficacy of prophylaxis treatment with marstacimab in participants who did not require Early Termination from the Phase 3 Study B7841005. Approximately 145 adolescent and adult participants 12 to <75 years of age with severe hemophilia A or moderately severe to severe hemophilia B (defined as FVIII activity <1% or FIX activity ≤2%, respectively) with or without inhibitors are expected to be enrolled in this study during which they will receive prophylaxis (defined as treatment by SC injection of marstacimab). The dosing regimen of marstacimab is 150 mg SC once weekly. All participants will be provided the PFP for administration of marstacimab in the study. Use of the PFS will be permitted at the investigator's discretion for those participants who have difficulty with administration of the PFP. Additionally, participants will be provided the PFS for use in this study in countries where the PFS is anticipated to be the only presentation available commercially. In addition, an optional, open-label, single arm, substudy using the PFP will be administered to the first approximately 20 participants rolling over from Study B7841005 who agree to participate in the substudy.

Official Title
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AN OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF MARSTACIMAB PROPHYLAXIS IN SEVERE (COAGULATION FACTOR ACTIVITY <1%) HEMOPHILIA A PARTICIPANTS WITH OR WITHOUT INHIBITORS OR MODERATELY SEVERE TO SEVERE HEMOPHILIA B PARTICIPANTS (COAGULATION FACTOR ACTIVITY ≤2%) WITH OR WITHOUT INHIBITORS

Conditions
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Hemophilia A, Hemophilia B

Intervention / Treatment
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* Drug: PF-06741086


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants will have a minimum body weight of 35 kg Participants have successfully completed participation in study B7841005, defined as did not require Early Termination from study B7841005 Exclusion Criteria: Previous or current treatment for or history of coronary artery disease, venous or arterial thrombosis (CTCAE Grade >3), or ischemic disease (except catherter-associated thrombosis) Abnormal renal function as defined by eGFR <30 mL.min/1.73 m(2) Known planned surgical procedure during the planned study period Unstable hepatic function as determined by the Investigator clinical assessment and review of the participant's most recent laboratory results, which would make the participant inappropriate for the study For participants known to be HIV+, worsening disease status as determined by the Investigator clinical assessment and review of participant's most recent laboratory results, to include recent locally available CD4 count (if available), which would make the participant inappropriate for the study Regular, concomitant therapy with immunomodulatory drugs (eg, IVIG, and routine systemic corticosteroids, rituximab) Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the study Participation in other study involving investigational drug(s) or investigational vaccine(s) within 30 days or 5 half-lives prior to or during study participation, with the exception of participation in study B7841005 Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the Investigator, and their respective family members

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06741086<br>300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria. | Drug: PF-06741086<br>* 300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria.<br>* Other names: marstacimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subject reporting Adverse Events |  | Baseline up to 7 years | 
| Number of subjects reporting Serious Adverse Events |  | Baseline up to 7 years | 
| Incidence and severity of thrombotic events |  | Baseline up to 7 years | 
| Incidence and severity of thrombotic microangiopathy |  | Baseline up to 7 years | 
| Number of subjects reporting Disseminated intravascular coagulalopathy/consumption coagulopathy |  | Baseline up to 7 years | 
| Incidence of clinically significant persistent NAb against marstacimab |  | Baseline up to 7 years | 
| Incidence and severity of injection site reaction |  | Baseline up to 7 years | 
| Clinically significant changes in vital signs from baseline |  | Baseline up to 7 years | 
| Incidence of clinically significant laboratory value abnormalities |  | Baseline up to 7 years | 
| Incidence of severe hypersensitivity and anaphylactic reactions |  | Baseline up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of bleeding episodes | Derived for each subject for each treatment period by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25) | Baseline up to 7 years | 
| Total coagulation factor product consumption |  | Baseline up to 7 years | 
| Incidence of joint bleeds |  | Baseline up to 7 years | 
| Incidence of spontaneous bleeds |  | Baseline up to 7 years | 
| Incidence of target joint bleeds |  | Baseline up to 7 years | 
| Incidence of total bleeds (treated and untreated) |  | Baseline up to 7 year | 
| Change in joints measured by the HJHS |  | Baseline up to 7 years | 
| Change in number of target joints per subject from baseline |  | Baseline up to 7 years | 
| Changes in Health Utilities Measure questionnaire data |  | Baseline up to 7 years | 
| Changes in Haem-A-QoL questionnaire data for participants ≥17 years of age |  | Baseline up to 7 years | 
| Changes in Haemo-QoL questionnaire data for participants 12 to <17 years of age |  | Baseline up to 7 years | 
| Total bypass product consumption |  | Baseline up to 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Factor VIII Inhibitor, Factor IX Inhibitor, PF-06741086, Marstacimab, Anti-TFPI