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)

Phase 2CompletedNCT03205163

Bioverativ, a Sanofi company16 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Hemophilia A

Interventions

Advate (Low Dose)BIOLOGICAL

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

Advate (High Dose)BIOLOGICAL

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

BIVV001 (Low Dose)BIOLOGICAL

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

Eligibility

Sex: MALEMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (10)

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

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During Advate Treatment Period

AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAE is defined as any AE that begins on or after the single dose of Advate but before the single dose of BIVV001. Serious AE (SAE) was defined as any AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.

Time frame: Up to Day 3 for Advate 25 IU/kg; up to Day 4 for Advate 65 IU/kg

Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During BIVV001 Treatment Period

AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAE is defined as any AE that begins on or after the study treatment (BIVV001) and within 28 days after BIVV001 administration. SAE was defined as any AE resulting in death, immediate risk of death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or a congenital/anomaly/birth defect, or any other medically important event.

Time frame: Up to 28 days after BIVV001 administration

Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During Advate Treatment Period

Number of Participants with Clinically Significant Abnormalities in Laboratory tests (including hematology, clinical chemistry, urinalysis, and coagulation and thrombosis markers) was reported.

Time frame: Up to Day 3 for Advate 25 IU/kg; up to Day 4 for Advate 65 IU/kg

Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During BIVV001 Treatment Period

Number of participants with clinically significant abnormalities (including hematology, clinical chemistry, urinalysis, and coagulation and thrombosis markers) was reported.

Data from ClinicalTrials.gov

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Secondary Outcomes

Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (Low Dose Comparison)

Cmax of Advate and BIVV001 at low dose was assessed and compared based on One-stage activated partial thromboplastin time (aPTT)-based clotting assay.

Time frame: For Advate: Pre-dose and Post dose at 0.5, 1, 6, 24, 48, and 72 hours; For BIVV001: Pre-dose and Post dose at 0.17, 0.5, 1, 3, 6, 9, 24, 48, 72, 96, 120, 168, and 240 hours

PK: Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (High Dose Comparison)

Cmax of Advate and BIVV001 at high dose was assessed and compared based on One-stage aPTT-based clotting assay.