B7841007 - 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

The primary objective of this study is to determine the **safety** and tolerability of long-term treatment with marstacimab in participants with severe **haemophilia** A or moderately severe to severe haemophilia B. This includes individuals aged 1 to <75 years, with or without inhibitors, where FVIII activity is <1% or FIX activity is ≤2%, respectively. The clinical relevance of this objective lies in ensuring that marstacimab can be safely administered over an extended period, which is crucial for managing these chronic conditions.

Secondary objectives include: - Evaluating the long-term efficacy of marstacimab in the same participant population, which is essential for understanding the sustained therapeutic benefits of the treatment. - Assessing the effect of marstacimab on health-related quality of life (HRQoL), providing insights into the broader impact of the treatment on patients' daily living and well-being.

The clinical trial involves a total of **203 participants** diagnosed with **hemophilia**, specifically targeting those with severe hemophilia A or moderately severe to severe hemophilia B. The study population consists exclusively of male subjects, ranging in age from 1 to less than 75 years. Participants were selected based on their successful completion of prior studies, specifically Studies B7841005 and B7841008, and their ability to comply with the study's requirements. The trial does not include female subjects and involves a vulnerable population. The health status of participants is characterized by their hemophilia condition, with FVIII activity less than 1% or FIX activity less than or equal to 2%, with or without inhibitors. The sponsor has not provided specific information regarding lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the long-term safety, tolerability, and efficacy of **marstacimab** prophylaxis in participants with severe **hemophilia A** or moderately severe to severe **hemophilia B**. This study is an open-label extension, allowing participants from previous studies (B7841005 and B7841008) to continue treatment. The trial is structured as a Phase 3 study, with a focus on assessing the safety endpoints, including adverse events (AEs), serious adverse events (SAEs), and the incidence of thrombotic events, among others. The trial will also evaluate secondary efficacy endpoints such as the annualized rate of treated bleeding episodes and changes in joint health.

The trial employs a non-randomized, open-label design, where all participants receive the investigational product, **marstacimab**, administered subcutaneously. The pharmaceutical forms used in the trial include a solution for injection in a pre-filled pen and a pre-filled syringe. The maximum daily dose is set at 150 mg or 300 mg, depending on the formulation, with a maximum treatment period of 84 days. The trial is expected to conclude by June 30, 2030, with recruitment having started on November 16, 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and previous study completion. Follow-up visits will be scheduled to monitor safety and efficacy outcomes, including laboratory tests and assessments of bleeding episodes. The end-of-study visit will conclude the participant's involvement, with a comprehensive evaluation of their health status and any long-term effects of the treatment.

The expected length of participant involvement is contingent upon their continued eligibility and adherence to the study protocol. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with study procedures, or withdrawal of consent. Participants and their legal guardians must provide informed consent before any study-specific activities are conducted, ensuring they are fully informed about the study's nature and requirements.

The clinical trial involves the administration of **marstacimab**, a biological medicinal product developed by Pfizer Inc. The experimental medication is provided in two pharmaceutical forms: a solution for injection in a pre-filled pen and a solution for injection in a pre-filled syringe. The active substance, marstacimab, is a protein of other origin, designated with the European substance number SUB193182. The pre-filled pen formulation is specifically designed for pediatric use and allows for a maximum daily dose of 150 mg, with a total maximum dose of 150 mg over a treatment period of 84 days. The pre-filled syringe formulation, not limited to pediatric use, permits a maximum daily dose of 300 mg, with a total maximum dose of 300 mg over the same treatment period. Both formulations are administered via the subcutaneous route.

Participants in the trial will receive marstacimab as a prophylactic treatment for severe hemophilia A or moderately severe to severe hemophilia B, with or without inhibitors. The trial aims to evaluate the long-term safety, tolerability, and efficacy of marstacimab. The administration of the drug will be monitored to ensure compliance with the dosing schedule, and the use of a syringe or pen for subcutaneous injection is specified, although these devices do not possess a CE mark. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned in the trial protocol.

Efficacy in this clinical trial will be assessed through a series of secondary endpoints designed to evaluate the impact of **marstacimab** prophylaxis in participants with severe Hemophilia A or moderately severe to severe Hemophilia B. The efficacy parameters include the annualized rate of treated bleeding episodes, incidence of joint bleeds, spontaneous bleeds, target joint bleeds, and total bleeds (both treated and untreated). Additionally, changes in joint health will be measured using the Hemophilia Joint Health Score (HJHS) for participants aged 4 years and older. The number of target joints will also be recorded.

Quality of life assessments will be conducted using the Haem-A-QoL for participants aged 17 years and older, and the Haemo-QoL for age-dependent versions for those aged 8 to 16 years. Health utility measures will be evaluated using the EQ-5D-5L for participants aged 12 years and older, and the EQ-5D-Y for self-assessment in participants aged 7 to 11 years, as well as proxy assessments for those aged 4 to 6 years. Total consumption of coagulation factor or bypass products will also be monitored. These efficacy endpoints will be reported annually for each year of participation in the study.