SEVENFACT® for Bleeding Events in Hemophilia With Inhibitors

Study Overview
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Brief Summary
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Phase IV multi-center, US-centric, open-label, safety study enrolling participants with Hemophilia A or 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.

Detailed Description
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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 up to 2 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 in order to achieve treatment of approximately 100 bleeding events. The study will target enrollment of a minimum of 23 participants on emicizumab prophylactic treatment and 5 participants on other treatments. Data Analysis: Sample Size Determination: Results from the Haven 1 study were used to calculate the annual bleeding rates (ABR) in individuals receiving prophylactic treatment. These were calculated at an ABR of three for participants receiving emicizumab prophylactic treatment and 20 for participants receiving other treatments. Based on these data, it was calculated that between 28 and 55 participants would be necessary to reach 100 BEs with a minimum of 23 participants on emicizumab prophylactic treatment and 5 participants on other treatments. 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.

Official Title
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Safety of SEVENFACT® for the Treatment of Bleeding Events in Patients With Hemophilia A or B With Inhibitors

Conditions
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Hemophilia A With Inhibitor, Hemophilia B With Inhibitor

Intervention / Treatment
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* Drug: coagulation factor VIIa [recombinant]-jncw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of hemophilia A or B with inhibitors. Be 12 years of age and older Be capable of understanding and willing to comply with the conditions of the protocol or have a legal guardian who is capable of understanding and complying with the conditions of the protocol Have read, understood, and documented written informed consent/assent Be able to provide medical evidence through prior medical history of previous inhibitor levels Be willing and able to use the ATHN mobile application or a paper diary to document BEs and medication usage Exclusion Criteria: Have a disorder of hemostasis in addition to Hemophilia A or B Have a known or suspected intolerance or hypersensitivity to SEVENFACT® or its ingredients Have a known allergy or hypersensitivity to rabbits or rabbit proteins Are receiving prophylactic treatment for bleeding with a drug or biologic that is not approved for this use by the FDA Have had implantation of an investigational medical device within the prior 6 months Have received an investigational drug within 30 days of the baseline visit Have an elective surgical procedure planned during the duration of their participation in the study* Have any life-threatening disease, or other disease or condition which, in the investigator's judgment, could pose a potential hazard to the patient or interfere with study participation or study outcome (e.g., a history of non responsiveness to bypassing products or thromboembolic disease) Should a participant require an unplanned surgery, the participant will not be withdrawn from the study unless the investigator deems it necessary. Instead, the participant will receive standard of care treatment as determined by the attending physician. If the participant is not withdrawn from the study, the participant's participation in the study will be paused until the investigator feels it is safe for them to continue.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: ATHN 16 is a phase IV multi-center, US-centric, open-label, safety study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hemophilia A and B Cases<br>SEVENFACT® has been approved for the treatment of bleeding events in individuals with hemophilia A or B with inhibitors. This study is intended to further investigate the safety and tolerability of SEVENFACT in participants with hemophilia A or B with inhibitors in the presence or absence of prophylactic therapies. Dosing will be at the discretion of the attending physician, and each participant will be supplied with the equivalent of nine 75 µg/kg doses, which aligns with the recommended dosing schedule as provided in SEVENFACT's United States Prescribing Information (USPI). In the event of a bleeding episode (BE), the participant will either self-administer the correct dose under the guidance of the treating investigator or the dose will be administered at a treatment facility. | Drug: coagulation factor VIIa [recombinant]-jncw<br>* a transgenically produced, activated, recombinant, human factor VII (rhFVIIa) protein with the brand name of SEVENFACT®. This protein is a clotting factor in the coagulation cascade that is produced in and purified from the milk of transgenic rabbits. SEVENFACT is approved for the treatment and control of bleeding episodes occurring in adults and adolescents (12 years of age and older) with hemophilia A or B with inhibitors.<br>* Other names: SEVENFACT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants and percentage of Safety Events (AEs) | Adverse Events and SAEs defined by the European Haemophilia Safety Surveillance System 2018 (EUHASS) and Serious Adverse Events (SAEs) as defined by the US Food and Drug Association. | From time of consent through BE onset until 3 days after last dose of SEVENFACT®. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Hemophilia B, bleeding event, prophylactic treatment