Phase 2
N=16
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)
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT03205163 ↗Enrolled (actual)
16
Serious AEs
6.5%
Results posted
Dec 2019
Primary outcome: Primary: Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During Advate Treatment Period — 2; 1; 1; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Advate (Low Dose) (Biological); Advate (High Dose) (Biological); BIVV001 (Low Dose) (Biological); BIVV001 (High Dose) (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Bioverativ, a Sanofi company
- Primary completion
- Nov 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During Advate Treatment Period |
2; 1; 1; 0 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) During BIVV001 Treatment Period |
3; 6; 1; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During Advate Treatment Period |
0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormalities in Laboratory Tests During BIVV001 Treatment Period |
0; 0 | — |
| PRIMARY Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay |
0; 0 | — |
| SECONDARY Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (Low Dose Comparison) |
51.8; 70.1 | 0.032 sig |
| SECONDARY PK: Maximum Observed Plasma Concentration (Cmax) for Advate and BIVV001 (High Dose Comparison) |
138; 161 | <0.001 sig |
| SECONDARY PK: Half-Life (t1/2) for Advate and BIVV001 (Low Dose Comparison) |
9.12; 37.61 | <0.001 sig |
| SECONDARY PK: Half-Life for Advate and BIVV001 (High Dose Comparison) |
13.15; 42.54 | <0.001 sig |
| SECONDARY PK: Total Body Clearance (CL) for Advate and BIVV001 (Low Dose Comparison) |
3.91; 0.558 | <0.001 sig |
| SECONDARY PK: Total Body Clearance (CL) for Advate and BIVV001 (High Dose Comparison) |
3.31; 0.505 | <0.001 sig |
| SECONDARY PK: Volume of Distribution at Steady State (Vss) for Advate and BIVV001 (Low Dose Comparison) |
55.9; 34.8 | 0.003 sig |
| SECONDARY PK: Volume of Distribution at Steady State (Vss) for Advate and BIVV001 (High Dose Comparison) |
58.3; 35.0 | <0.001 sig |
| SECONDARY PK: Area Under the Concentration Time Curve (AUC) From Time 0 to Infinity (AUCinfinity) for Advate and BIVV001 (Low Dose Comparison) |
638; 4470 | <0.001 sig |
| SECONDARY PK: Area Under the Concentration Time Curve From Time 0 to Infinity (AUCinfinity) for Advate and BIVV001 (High Dose Comparison) |
1960; 12800 | <0.001 sig |
| SECONDARY PK: Mean Residence Time (MRT) for Advate and BIVV001 (Low Dose Comparison) |
12.54; 56.93 | <0.001 sig |
| SECONDARY PK: Mean Residence Time (MRT) for Advate and BIVV001 (High Dose Comparison) |
15.66; 67.66 | <0.001 sig |
| SECONDARY PK: Incremental Recovery (IR) for Advate and BIVV001 (Low Dose Comparison) |
2.0; 2.72 | 0.063 |
| SECONDARY PK: Incremental Recovery (IR) for Advate and BIVV001 (High Dose Comparison) |
2.11; 2.48 | <0.001 sig |
| SECONDARY PK: Time to 1% Above Baseline for FVIII Activity for Advate and BIVV001 (Low Dose Comparison) |
56.97; 260.53 | <0.001 sig |
| SECONDARY PK: Time to 1% Above Baseline for FVIII Activity for Advate and BIVV001 (High Dose Comparison) |
78.48; 350.34 | <0.001 sig |
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.
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%, then a repeat endogenous FVIII activity level was performed using the one stage clotting assay from the central laboratory. If the repeated result was =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.
Data sourced from ClinicalTrials.gov (NCT03205163). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.