Back to resultsPharmacokinetic Assessment of Standard Half-Life (SHL) FVIII, Extended Half-Life (EHL) FVIII, and Efanesoctocog Alfa (BIVV001) in Severe Hemophilia A
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 1
Locations
Bulgaria
Study Type
Interventional
Intervention
Efanesoctocog alfa
Octocog alfa
Rurioctocog alfa pegol
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility Criteria
Inclusion Criteria:
- Severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII activity.
- Previous treatment for hemophilia A, defined as at least 150 days documented prior exposure to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products at Day 1.
- Platelet count ≥100,000 cells/µL at Screening.
- 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 enrollment. (CD4 lymphocyte count >200 cells/mm³ - Viral load of <400 copies/mL).
Exclusion Criteria:
- Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
- Serious active bacterial, fungal 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.
- History of a positive inhibitor test defined as ≥0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant.
- Positive inhibitor result, defined as ≥0.6 BU/mL at Screening.
- Major surgery within 8 weeks of Screening.
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number :1000001
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
efanesoctocog alfa (BIVV001)
Arm Description
Each participant will be sequentially dosed with three single intravenous (IV) doses of first rFVIII (Advate®), second Polyethylene Glycol (PEG)-rFVIII (Adynovi® or Adynovate®), and lastly, BIVV001
Outcomes
Primary Outcome Measures
Half-life of BIVV001
Half-life of SHL rFVIII
Half-Life of EHL rFVIII
Secondary Outcome Measures
Assessment of pharmacokinetic (PK) parameter : maximum activity (Cmax)
Assessment of PK parameter : clearance (CL)
Assessment of PK parameter : volume of distribution at steady state (Vss)
Assessment of PK parameter : area under the activity time curve extrapolated to infinity (AUC∞)
Assessment of PK parameter : mean residence time (MRT)
Assessment of PK parameter : incremental recovery (IR)
Number of participants with Adverse events (AE), serious AEs and treatment-emergent AEs (TEAEs)
Development of inhibitors (neutralizing antibodies directed against FVIII)
Number of participants with development of inhibitors
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05042440
Brief Title
Pharmacokinetic Assessment of Standard Half-Life (SHL) FVIII, Extended Half-Life (EHL) FVIII, and Efanesoctocog Alfa (BIVV001) in Severe Hemophilia A
Official Title
A Phase 1, Single-Site, Open-Label Study to Assess Pharmacokinetics of Efanesoctocog Alfa (BIVV001), Standard Half-Life and Extended Half-Life FVIII After Each Single Intravenous Injection in a Fixed Sequence, in Previously Treated Adults With Severe Hemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 11, 2021 (Actual)
Primary Completion Date
November 24, 2021 (Actual)
Study Completion Date
November 24, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary objective
• To assess the half-life of BIVV001, Standard Half-Life (SHL) rFVIII and Extended Half-Life (EHL) rFVIII after a single intravenous (IV) injection
Secondary objectives
To characterize additional pharmacokinetic (PK) parameters of BIVV001, SHL rFVIII and EHL rFVIII after a single IV injection
To evaluate the safety and tolerability of a single IV injection of BIVV001
Detailed Description
This is a Phase 1, single center, open-label, sequential treatment, 3-period fixed sequence study to assess PK profiles of BIVV001, SHL and EHL rFVIII after a single IV injection in male, previously treated patients, 18-65 years of age, with severe hemophilia A (defined as <1 IU/dL [<1%] endogenous FVIII).
The expected duration of the study is up to approximately 67 days including
Screening and washout up to 28 days,
Advate® dosing, PK sampling, including washout: approximately 4 days,
Adynovi® dosing and PK sampling, including washout: approximately 7 days,
BIVV001 dosing and PK sampling: approximately 14 days, Remainder of Safety Observation Period: approximately 14 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
efanesoctocog alfa (BIVV001)
Arm Type
Experimental
Arm Description
Each participant will be sequentially dosed with three single intravenous (IV) doses of first rFVIII (Advate®), second Polyethylene Glycol (PEG)-rFVIII (Adynovi® or Adynovate®), and lastly, BIVV001
Intervention Type
Drug
Intervention Name(s)
Efanesoctocog alfa
Other Intervention Name(s)
BIVV001
Intervention Description
Solution for injection Intravenous
Intervention Type
Drug
Intervention Name(s)
Octocog alfa
Other Intervention Name(s)
Advate®
Intervention Description
Solution for injection Intravenous
Intervention Type
Drug
Intervention Name(s)
Rurioctocog alfa pegol
Other Intervention Name(s)
Adynovi®
Intervention Description
Solution for injection Intravenous
Primary Outcome Measure Information:
Title
Half-life of BIVV001
Time Frame
BIVV001 period: Predose, and post-dose from 0.17 hr to 336 hr, and at day 28
Title
Half-life of SHL rFVIII
Time Frame
Advate® period: Predose, and post-dose from 0.17 hr to 72 hr
Title
Half-Life of EHL rFVIII
Time Frame
Adynovi® period: Predose, and post-dose from 0.17 hr to 120 hr
Secondary Outcome Measure Information:
Title
Assessment of pharmacokinetic (PK) parameter : maximum activity (Cmax)
Time Frame
Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001
Title
Assessment of PK parameter : clearance (CL)
Time Frame
Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001
Title
Assessment of PK parameter : volume of distribution at steady state (Vss)
Time Frame
Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001
Title
Assessment of PK parameter : area under the activity time curve extrapolated to infinity (AUC∞)
Time Frame
Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001
Title
Assessment of PK parameter : mean residence time (MRT)
Time Frame
Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001
Title
Assessment of PK parameter : incremental recovery (IR)
Time Frame
Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001
Title
Number of participants with Adverse events (AE), serious AEs and treatment-emergent AEs (TEAEs)
Time Frame
From Day 1 up to 28 days after administration of BIVV001 (total 39 days including Advate® and Adynovi® period)
Title
Development of inhibitors (neutralizing antibodies directed against FVIII)
Description
Number of participants with development of inhibitors
Time Frame
Advate® period: Pre-dose; Adynovi® period: Pre-dose; BIVV001 period: Pre-dose and at day 14 and 28 after administration.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII activity.
Previous treatment for hemophilia A, defined as at least 150 days documented prior exposure to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products at Day 1.
Platelet count ≥100,000 cells/µL at Screening.
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 enrollment. (CD4 lymphocyte count >200 cells/mm³ - Viral load of <400 copies/mL).
Exclusion Criteria:
Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
Serious active bacterial, fungal 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.
History of a positive inhibitor test defined as ≥0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant.
Positive inhibitor result, defined as ≥0.6 BU/mL at Screening.
Major surgery within 8 weeks of Screening.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences and Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :1000001
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
37538505
Citation
Lissitchkov T, Willemze A, Jan C, Zilberstein M, Katragadda S. Pharmacokinetics of recombinant factor VIII in adults with severe hemophilia A: fixed-sequence single-dose study of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa. Res Pract Thromb Haemost. 2023 May 13;7(4):100176. doi: 10.1016/j.rpth.2023.100176. eCollection 2023 May.
Results Reference
result
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Pharmacokinetic Assessment of Standard Half-Life (SHL) FVIII, Extended Half-Life (EHL) FVIII, and Efanesoctocog Alfa (BIVV001) in Severe Hemophilia A
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