SEVENFACT® for Bleeding Events in Hemophilia With Inhibitors

Primary Objective: To evaluate the safety of SEVENFACT® when used to treat bleeding episodes in participants with Hemophilia A or B with inhibitors either with or without prophylactic treatment Study Design: Phase IV multi-center, US-centric, open-label, safety study enrolling participants with Hemophilia A and B with inhibitors12 years of age and older, who are either on long term prophylactic treatment (e.g., emicizumab) at risk of experiencing a breakthrough bleeding event (BE), or who are not on prophylactic treatment who may need to control a BE. Study Duration: Participants will be followed longitudinally from the time of enrollment to the end of their participation in the study. The maximal study duration for any participant in the study will be approximately 4 years from the time of enrollment. Target Accrual: This is a multi-site study in which it is anticipated approximately 28 to 55 participants will be enrolled. The study will target enrollment of participants with Hemophilia A and B with inhibitors on prophylaxis with FDA-approved therapies. Enrollment will continue until September 30, 2026, or until the time that the 28th participant is enrolled, whichever comes first. Data Analysis: Sample Size Determination: Results from the study (March 19, 2024, data transfer) with 19 participants enrolled and 3 participant discontinuations were used to calculate the annual bleeding rate for participants receiving prophylactic treatment. Adjusted annualized bleeding rate was calculated at 0.58. Based on these data, up to 28 participants with hemophilia A and B with inhibitors on FDA-approved prophylaxis treatments will be attempted to enroll. Analysis Populations: The Safety Analysis Set is defined as all participants who received at least a single dose of SEVENFACT®. All analyses of safety will be performed based on the safety population, and participants will be analyzed according to the dose of SEVENFACT® that they actually received. Baseline Characteristics: Baseline characteristics will be summarized using descriptive statistics for continuous variables, and frequencies and percentages for categorical variables. Safety Evaluations: All Adverse Events (AEs) will be graded for severity utilizing Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and coded using Medical Dictionary of Regulatory Activities (MedDRA) version 23.x. The number and percentage of participants with treatment-emergent AEs (TEAEs), serious AEs (SAEs), serious TEAEs and treatment related TEAEs (i.e., adverse drug reactions \[ADRs\]) will be presented for all participants. The number of TEAEs, as well as the number and percentage of participants with TEAEs, serious TEAEs, and treatment-related TEAEs will be presented by MedDRA System Organ Class (SOC) and preferred term for all participants. The number and percentage of participants with treatment-emergent adverse event and/or allergic and anaphylactic reactions will be presented for all participants. Efficacy Evaluations: There are no pre-specified efficacy endpoints. Interim Analysis: An interim analysis will be conducted after 20 participants have been enrolled into the study. The analysis will seek to characterize baseline, disease, dosing and safety outcome profiles of participants treated with SEVENFACT.