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)

Bioverativ

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hemophilia A

Treatments: Biological: BIVV001 (Low Dose); Biological: Advate (Low Dose); Biological: BIVV001 (High Dose); Biological: Advate (High Dose)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03205163

242HA101 (Other Identifier)

TDU16220

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Biological: BIVV001 (Low Dose)

Biological: Advate (Low Dose)

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

Experimental group

Description:

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.

Treatment:

Biological: BIVV001 (High Dose)

Biological: Advate (High Dose)