A Study to Learn About How Changing Therapy From Emicizumab to Marstacimab Affects People With the Severe Hemophilia A.

This is a non-randomized open-label study in approximately 10-15 adolescent and adult participants between ages 12 to <75 years with severe hemophilia A (defined as FVIII activity <1%) without inhibitors who are currently on treatment with emicizumab for ≥6 months. The study is designed to assess the safety and PK/PD during a 4-month treatment period with marstacimab 150 mg SC QW after a minimum 14-day wash-out period following discontinuation of emicizumab. Assessment of safety will be conducted by summarizing AEs and SAEs reported during the study, from the time each participant provides informed consent through and including a minimum of 28 calendar days after last dose of study intervention. Participants will continue to use their standard of care factor replacement for breakthrough bleeds during the course of the study. PK, PD, and ADA measurements will support the clinical safety data. The anticipated study duration for an individual participant is approximately 6 months. After completion of marstacimab treatment period participants will resume their standard of care prophylactic treatment after a 14-day wash-out period following the last dose of marstacimab. Roll-over into an optional study treatment extension period will be available to participants who wish to continue prophylaxis with marstacimab in countries where it is not commercially available.

Inclusion criteria

• Male and 12 to <75 years of age with a minimum body weight of 35 kg at the time of signing the informed consent.
• Diagnosis of severe hemophilia A (FVIII activity <1%) without inhibitors.
• On emicizumab therapy at a standard clinical dose for ≥6 months.

Exclusion criteria

• Previous or current treatment for or history of coronary artery diseases, venous or arterial thrombosis, or ischemic disease.
• Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Known hemostatic defect other than hemophilia A.
• Current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s).
• Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.
• Platelet count <100,000/μl or hemoglobin <10 g/dL.
• Clinically significant renal or hepatic function abnormality based on laboratory results at screening, or known kidney or liver disease.
• CD4 cell count ≤200/μl if HIV positive.
• Screening 12-lead ECG that demonstrates clinically significant abnormalities that, in the opinion of the investigator, may affect participant safety or interpretation of study results.
• Known planned surgical procedure.
• Hypersensitivity or allergic reaction to hamster protein or other components of the study intervention.
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor-delegate employees directly involved in the conduct of the study and their family members.