A Safety, Tolerability, and Pharmacokinetics Study of a Single Intravenous Injection of Recombinant Coagulation Factor VIII Fc - Von Willebrand Factor - XTEN Fusion Protein (rFVIIIFc-VWF-XTEN) (BIVV001) in Previously Treated Adults With Severe Hemophilia A (EXTEN-A)

NCT ID: NCT03205163

Last Updated: 2022-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-28
• Study Completion Date: 2018-11-12

Brief Summary

The primary purpose was to assess the safety and tolerability of a single intravenous (IV) administration of BIVV001 in adult previously treated patients (PTPs) with severe hemophilia A.

Conditions

Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Low Dose Cohort: Advate 25 IU/kg Then BIVV001 25 IU/kg

Participants received a single intravenous (IV) dose of Advate 25 international units per kilogram (IU/kg) on Day 1 of Advate treatment period (3 days) followed by a single IV dose of BIVV001 25 IU/kg in BIVV001 treatment period (BTP) (28 days). Advate treatment period (ATP) consisted of a washout of at least 72 hours which was started from the time of Advate dosing.

Group Type: EXPERIMENTAL

Advate (Low Dose)

Intervention Type: BIOLOGICAL

Participants received a single IV low dose of Advate 25 IU/kg.

BIVV001 (Low Dose)

Intervention Type: BIOLOGICAL

Participants received single IV low dose of BIVV001 25 IU/kg.

High Dose Cohort: Advate 65 IU/kg Then BIVV001 65 IU/kg

Participants received a single IV dose of Advate 65 IU/kg on Day 1 of ATP (4 days) followed by a single IV dose of BIVV001 65 IU/kg in BTP (28 days). ATP consisted of a washout of at least 96 hours which was started from the time of Advate dosing.

Group Type: EXPERIMENTAL

Advate (High Dose)

Intervention Type: BIOLOGICAL

Participants received a single IV high dose of Advate 65 IU/kg.

BIVV001 (High Dose)

Intervention Type: BIOLOGICAL

Participants received single IV high dose of BIVV001 65 IU/kg.

Interventions

Advate (Low Dose)

Participants received a single IV low dose of Advate 25 IU/kg.

Intervention Type: BIOLOGICAL

Advate (High Dose)

Participants received a single IV high dose of Advate 65 IU/kg.

Intervention Type: BIOLOGICAL

BIVV001 (Low Dose)

Participants received single IV low dose of BIVV001 25 IU/kg.

Intervention Type: BIOLOGICAL

BIVV001 (High Dose)

Participants received single IV high dose of BIVV001 65 IU/kg.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Ability of the participant, or his legally authorized representative (e.g., parent or legal guardian) if applicable in accordance with local regulations, to understand the purpose and risks of the study and provide signed and dated informed consent/assent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
• Severe hemophilia A, defined as less than (<) 1 international units per deciliter (IU/dL) (<1 percent [%]) endogenous FVIII at screening as determined by the one-stage clotting assay from the central laboratory. If the initial screening result was greater than or equal to (>=) 1%, then a repeat endogenous FVIII activity level was performed using the one stage clotting assay from the central laboratory. If the repeated result was < 1 IU/dL (<1%), then the participant met this inclusion requirement.
• Previous treatment for hemophilia A, defined as at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
• Platelet count >=100,000 cells/ microliter (mcL) at screening (test performed by the central laboratory and reviewed prior to the Day 1 Advate dose).
• A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to Day 1 Advate dose: cluster of differentiation 4 (CD4) lymphocyte count greater than (>) 200 cells/millimeter (mm)^3; viral load of <400 copies/mL.

Exclusion Criteria

Medical History:

• Any concurrent clinically significant major disease that, in the opinion of the Investigator, made the participant unsuitable for enrollment.
• Serious active bacterial or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening.
• Other known coagulation disorder(s) in addition to hemophilia A.
• History of hypersensitivity or anaphylaxis associated with any FVIII product.
• Known or suspected allergy to mice, hamsters, or any ingredient in Advate.
• History of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors not excluded the participant.

Medications and Procedures:

• Current enrollment or participation within 30 days prior to screening in any other investigational study.

Other:

• Inability to comply with study requirements as assessed by the Investigator.
• Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bioverativ, a Sanofi company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California Los Angeles Medical Center

Los Angeles, California, United States

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Michigan State University

East Lansing, Michigan, United States

Mississippi Center for Advanced Medicine

Madison, Mississippi, United States

Hemophilia Center of Western PA

Pittsburgh, Pennsylvania, United States

University of Washington

Seattle, Washington, United States

Nara Medical University Hospital

Kashihara-shi, Nara, Japan

Tokyo Medical University Hospital

Shinjuku-Ku, Tokyo-To, Japan

Ogikubo Hospital

Tokyo, Tokyo-To, Japan

Countries

United States; Japan

References

Konkle BA, Shapiro AD, Quon DV, Staber JM, Kulkarni R, Ragni MV, Chhabra ES, Poloskey S, Rice K, Katragadda S, Fruebis J, Benson CC. BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A. N Engl J Med. 2020 Sep 10;383(11):1018-1027. doi: 10.1056/NEJMoa2002699.

Reference Type: DERIVED

PMID: 32905674 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

242HA101

Identifier Type: OTHER

Identifier Source: secondary_id

TDU16220

Identifier Type: -

Identifier Source: org_study_id