SEVENFACT® for Bleeding Events in Hemophilia With Inhibitors

• Sponsor: American Thrombosis and Hemostasis Network (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04647227
• Collaborator: LFB USA, Inc. (Industry)
• Enrollment: 55
• Locations: 24
• Arm: 1
• Anticipated Duration (Months): 47.1
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A With Inhibitor; Hemophilia B With Inhibitor	Drug: coagulation factor VIIa [recombinant]-jncw	Phase 4

Detailed 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: ATHN 16 is a phase IV multi-center, US-centric, open-label, safety studyATHN 16 is a phase IV multi-center, US-centric, open-label, safety study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of SEVENFACT® for the Treatment of Bleeding Events in Patients With Hemophilia A or B With Inhibitors
• Actual Study Start Date: Jun 28, 2021
• Anticipated Primary Completion Date: Oct 31, 2023
• Anticipated Study Completion Date: Jun 1, 2025

Arms and Interventions

Arm

Intervention/Treatment

Other: Hemophilia A and B Cases 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; 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.; Other Names: SEVENFACT

Outcome Measures

Primary Outcome Measures

1. Number of participants and percentage of Safety Events (AEs) [From time of consent through BE onset until 3 days after last dose of SEVENFACT®.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Hemophilia and Thrombosis Center at Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Orthopaedic Institute for Children	Los Angeles	California	United States	90007
3	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
4	Center for Inherited Blood Disorders	Orange	California	United States	92868
5	University of California at Davis UC Davis Hemostasis and Thrombosis Center	Sacramento	California	United States	95817
6	Children's National Hemophilia Center	Washington	District of Columbia	United States	20010
7	Hemophilia of Georgia Center for Bleeding and Clotting Disorders of Emory, Adult Division	Atlanta	Georgia	United States	31404
8	Willett Children's Hospital at Memorial University Medical Center	Savannah	Georgia	United States	31404
9	Louisiana Center for Bleeding and Clotting Disorders, Tulane	New Orleans	Louisiana	United States	70112
10	Louisiana Center for Advanced Medicine	Slidell	Louisiana	United States	70461
11	Maine Hemophilia and Thrombosis Center	Scarborough	Maine	United States	04074
12	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
13	Henry Ford Health System	Detroit	Michigan	United States	48202
14	MSU Center for Bleeding and Clotting Disorders	Lansing	Michigan	United States	48912
15	Center for Bleeding and Clotting Disorders, University of Minnesota	Minneapolis	Minnesota	United States	55455
16	Mayo Comprehensive Hemophilia Center	Rochester	Minnesota	United States	55905
17	Mississippi Center for Advanced Medicine	Madison	Mississippi	United States	39110
18	Kansas City Regional Hemophilia Center	Kansas City	Missouri	United States	64108
19	Northwell Health, Long Island Jewish	New Hyde Park	New York	United States	11040
20	Brody School of Medicine at East Carolina University	Greenville	North Carolina	United States	27834
21	University Hospitals Health System Cleveland	Cleveland	Ohio	United States	44106
22	Oklahoma Center for Bleeding and Clotting Disorders	Oklahoma City	Oklahoma	United States	73104
23	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
24	Gulf States Hemophilia and Thrombophilia Center-University of Texas Health Science Center @Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• American Thrombosis and Hemostasis Network
• LFB USA, Inc.

Investigators

• Principal Investigator: Tammuella Chrisentery-Singleton, MD, Louisiana Center for Advanced Medicine
• Principal Investigator: Mark Reding, MD, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: American Thrombosis and Hemostasis Network
• ClinicalTrials.gov Identifier: NCT04647227
• Other Study ID Numbers: ATHN 16
• First Posted: Nov 30, 2020
• Last Update Posted: Aug 12, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by American Thrombosis and Hemostasis Network: Hemophilia A; Hemophilia B; bleeding event; prophylactic treatment
• Additional relevant MeSH terms: Hemophilia A; Hemophilia B; Hemorrhage

Study Results

No Results Posted as of Aug 12, 2022