Phase 3 study for people with Haemophilia

Reproduced exactly, unedited. Written for researchers rather than for patients.

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.
• Participants aged 1 to 5 years must be at least 5 kgs at time of consent.
• Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B
• Participants must have at least 1 year (if aged 6 to 17 years), or at least 3 months (if aged 1 to 5 years) 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 over the above specified timeframe 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 for participants aged 6 to 17 years. Participants from 1 to 5 years do not require a minimum documented number of exposure days
• 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 for participants aged 6 to 17 years, for at least 3 months prior to consent for participants from 1 to 5 years

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.
• Participants aged 6 to 17 years: 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 aged 1 to 5 years of age with at least 3 months' on-demand bypass treatment regimen and at least 1 treated hemophilic bleeding in the last 3 months or at least 2 treated hemophilic bleedings in the last 6 months documented prior to the time of informed consent
• Participants aged 6 to 17 years must be on an on-demand bypass treatment regimen during the 12 months prior to informed consent
• Participants aged 1 to 5 years of age must be on an on-demand bypass treatment regimen during the 3 months prior to informed consent

Exclusion Criteria:

• Known coronary artery, thrombotic, or ischemic disease, or current evidence of congenital or acquired thrombophilic disease such as Anti-thrombin III deficiency, Factor V Leiden mutation, prothrombin 20210 mutation, protein C deficiency, protein S deficiency 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
• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. Participants aged 1 to 5 years with known hepatitis B or C will also be excluded
• Known HIV-positive for participants aged 1 to 5 years of age
• 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. Some of these agents may be permitted if it is authorized for use in the respective country, is part of the standard of care in the study population, its use is short term and on a PRN basis and following discussion with the Pfizer medical monitor.
• 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, for participants aged 6 to 17 years
• 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