Overview

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called marstacimab) for the potential treatment of hemophilia in pediatric patients.

This study will enroll pediatric participants from ages 1 to 17 years in a sequential manner. The study will open enrollment to adolescent participants aged 12 to 17 years first. Then children aged 6 to 11 years will be permitted to enroll. Lastly, children aged 1 to 5 years will be permitted to enroll.

This study will enroll participants who:

• have severe Hemophilia A or moderately severe to severe Hemophilia B (with or without inhibitors)
• have accurate historical records documenting all factor VIII, factor IX, or bypass agent infusions and hemophilia bleed events for at least 1 year prior to entering the study
• if a non-inhibitor patient, must be on a stable routine prophylaxis regimen with factor VIII or factor IX replacement products for at least 12 months prior to study entry
• if an inhibitor patient, must be on an on-demand bypass treatment regimen during the 12 months prior to study entry

All participants in this study will receive marstacimab to use prophylactically. Marstacimab will be given once a week as a subcutaneous (under the skin) shot. The first dose of marstacimab will be given at the study site by the study site staff. During the 12-month treatment period, weekly doses of marstacimab can be given at home, or if preferred, the doses may be given by the study site staff.

To help us determine if the study medicine is safe and effective, we will compare participant experiences when they are taking the study medicine to a historical period when they were not. Researchers want to see if the study medicine works to prevent the bleeding episodes commonly experienced by patients with Hemophilia.

Participants will be in this study for about 14 months (approximately 1 month in a Screening period, 12 months receiving treatment, and 1 month in a follow-up period) during which they will visit the study site at least 10 times. If preferred, and if local regulations allow it, 2 of the study visits can be completed at the participant's home instead of at the study site. There will also be 6 scheduled telephone calls approximately every 2 months.

Eligibility

Inclusion Criteria:

• Male participants of appropriate age and required minimum weight
• Participants aged 12 to 17 years must be at least 25 kgs at time of consent.
• Participants aged 6 to 11 years must be at least 19 kgs at time of consent.
• Minimum weight requirement for participants aged 1 to 5 years is to be determined.
• Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B
• Participants must have at least 1 year of diary and/or medical records available in which exogenous FVIII or FIX replacement or bypass agent infusions and hemophilic bleeding episodes were consistently documented over the 12 months prior to the time of consent.

        Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following
        criteria:
          -  No current detectable inhibitor and no documented history of inhibitors in the 5 years
             prior to consent
          -  Must have at least 50 exposure days to FVIII/FIX replacement products
          -  Must be at least 80% compliant with a stable and effective routine prophylaxis regimen
             with FVIII/FIX replacement products, for at least 12 months prior to consent
        Participants who are enrolled into the Inhibitor Cohort must also meet the following
        criteria:
          -  Documentation of current high titer inhibitor (≥5 BU/mL); or current low titer
             inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or FIX
             recovery <60% of expected within previous 12 months prior to the time of consent
          -  Participants who have documented inhibitors while on factor-replacement therapy but
             who do not meet the high quantitative inhibitor criteria described in the prior bullet
             at the time of screening (eg, participant with a previously documented high-titer
             inhibitor ≥5 BU/mL) and whose condition precludes re-challenge with FVIII or FIX
             replacement may be considered for eligibility on a case-by-case basis with discussion
             and agreement from the Pfizer medical monitor.
          -  Hemophilia A participants with on-demand treatment regimen with ≥12 bleeding episodes
             or hemophilia B participants with on-demand treatment regimen with ≥8 bleeding
             episodes (spontaneous or traumatic) necessitating treatment with bypass factor in the
             12 months prior to informed consent
          -  Participants must be on an on-demand bypass treatment regimen during the 12 months
             prior to informed consent
        Exclusion Criteria:
          -  Known coronary artery, thrombotic, or ischemic disease, including congenital or
             acquired thrombophilic disease such as Anti-thrombin III, Factor V Leiden mutation,
             prothrombin 20210 mutation, protein C activity, protein S activity and
             antiphospholipid syndrome.
          -  Known planned surgical procedure during the planned study period
          -  Known hemostatic defect other than hemophilia A or B
          -  Abnormal hematology, renal or hepatic function laboratory results at screening
          -  Other acute or chronic medical or psychiatric condition that may increase the risk
             associated with study participation or investigational product administration or may
             interfere with the interpretation of study results and, in the judgment of the
             investigator
          -  Individuals with known allergic reaction or hypersensitivity to hamster protein or
             other components of the study intervention
          -  Current routine prophylaxis with bypassing agent, non-coagulation non-factor
             replacement therapy (eg, emicizumab), or any previous treatment with a gene therapy
             product for treatment of hemophilia
          -  Participants with inhibitors who are being treated using a prophylaxis treatment
             regimen with a bypass agent, and, participants who have previously received
             non-factor-based hemophilia therapy (eg, fitusiran, concizumab, emicizumab) will be
             considered on a case-by-case basis, only after discussion and agreement between the
             investigator and the Pfizer medical monitor
          -  Regular use of immunomodulatory medications (eg, IVIG, routine systemic
             corticosteroids, rituximab)
          -  Use of systemic antifibrinolytics, medications that may increase the risk of bleeding,
             and certain non-steroidal anti-inflammatory drugs within 120 hours of first dose of
             study intervention and while on study
          -  Ongoing or planned use of ITI, or prophylaxis with FVIII or FIX replacement at any
             time after initiation of treatment with study intervention
          -  Participation in other studies involving investigational drug(s) or investigational
             vaccine(s) within 30 days (or as determined by local requirements) or 5 half-lives
             prior to study entry or during study participation
          -  Previous exposure to marstacimab during participation in other marstacimab clinical
             studies
          -  CD4 cell count ≤200/uL if HIV-positive
          -  Abnormal ECG of clinical relevance that may affect participant safety or
             interpretation of study results
          -  Investigator site staff members directly involved in the conduct of the study and
             their family members, site staff members otherwise supervised by the investigator, and
             sponsor and sponsor delegate employees directly involved in the conduct of the study
             and their family members