SEVENFACT® for Bleeding Events in Hemophilia With Inhibitors

Hemophilia A With Inhibitor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04647227
• Other study ID #: ATHN 16
• Status: Recruiting
• Phase: Phase 4
• Start date: June 28, 2021
• Est. completion date: June 1, 2025

Study information

• Verified date: November 2023
• Source: American Thrombosis and Hemostasis Network
• Contact: Carol Fedor, ND, RN, CCRC
• Phone: (800)-360-2846
• Email: cfedor[@]athn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: June 1, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Have a diagnosis of hemophilia A or B with inhibitors.

2. Be 12 years of age and older

3. 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

4. Have read, understood, and documented written informed consent/assent

5. Be able to provide medical evidence through prior medical history of previous inhibitor levels

6. Be willing and able to use the ATHN mobile application or a paper diary to document BEs and medication usage

Exclusion Criteria:

1. Have a disorder of hemostasis in addition to Hemophilia A or B

2. Have a known or suspected intolerance or hypersensitivity to SEVENFACT® or its ingredients

3. Have a known allergy or hypersensitivity to rabbits or rabbit proteins

4. Are receiving prophylactic treatment for bleeding with a drug or biologic that is not approved for this use by the FDA

5. Have had implantation of an investigational medical device within the prior 6 months

6. Have received an investigational drug within 30 days of the baseline visit

7. Have an elective surgical procedure planned during the duration of their participation in the study*

8. 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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitor
• Hemophilia B
• Hemophilia B With Inhibitor
• Hemorrhage

Intervention

Drug:
• coagulation factor VIIa [recombinant]-jncw
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.

Locations

Country	Name	City	State
United States	Hemophilia of Georgia Center for Bleeding and Clotting Disorders of Emory, Adult Division	Atlanta	Georgia
United States	Massachusetts General Hospital Comprehensive Hemophilia and Thrombosis Treatment Center	Boston	Massachusetts
United States	University Hospitals Health System Cleveland	Cleveland	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	Brody School of Medicine at East Carolina University	Greenville	North Carolina
United States	Gulf States Hemophilia and Thrombophilia Center-University of Texas Health Science Center @Houston	Houston	Texas
United States	Kansas City Regional Hemophilia Center	Kansas City	Missouri
United States	MSU Center for Bleeding and Clotting Disorders	Lansing	Michigan
United States	Arkansas Center for Bleeding Disorders	Little Rock	Arkansas
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Orthopaedic Institute for Children	Los Angeles	California
United States	Mississippi Center for Advanced Medicine	Madison	Mississippi
United States	Center for Bleeding and Clotting Disorders, University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Northwell Health, Long Island Jewish	New Hyde Park	New York
United States	Louisiana Center for Bleeding and Clotting Disorders, Tulane	New Orleans	Louisiana
United States	Oklahoma Center for Bleeding and Clotting Disorders	Oklahoma City	Oklahoma
United States	Arnold Palmer Hospital for Children - The Haley Center for Children's Cancer and Blood Disorders	Orlando	Florida
United States	Arizona Hemophilia and Thrombosis Center at Phoenix Children's Hospital	Phoenix	Arizona
United States	Mayo Comprehensive Hemophilia Center	Rochester	Minnesota
United States	University of California at Davis UC Davis Hemostasis and Thrombosis Center	Sacramento	California
United States	Willett Children's Hospital at Memorial University Medical Center	Savannah	Georgia
United States	Maine Hemophilia and Thrombosis Center	Scarborough	Maine
United States	Louisiana Center for Advanced Medicine	Slidell	Louisiana
United States	Children's National Hemophilia Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
American Thrombosis and Hemostasis Network	LFB USA, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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®.