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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02083965




Registration number
NCT02083965
Ethics application status
Date submitted
7/03/2014
Date registered
11/03/2014
Date last updated
19/12/2020

Titles & IDs
Public title
Pharmacokinetics of rFVIIIFc at Two Vial Strengths
Scientific title
A Randomized, Open-Label, Crossover Study to Evaluate the Pharmacokinetics of 2 Vial Strengths of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in Previously Treated Subjects With Severe Hemophilia A
Secondary ID [1] 0 0
2013-003013-18
Secondary ID [2] 0 0
997HA307
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - rFVIIIFc

Experimental: rFVIIIFc 1000 / 3000 PK Assessment - A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial.

Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.

Experimental: rFVIIIFc 3000 / 1000 PK Assessment - A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial.

Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.


Treatment: Other: rFVIIIFc
Administered as specified in the treatment arm.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay
Timepoint [1] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Primary outcome [2] 0 0
Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay
Timepoint [2] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [1] 0 0
Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay
Timepoint [1] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [2] 0 0
Half-life (t½) as Measured by aPTT Clotting Assay
Timepoint [2] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [3] 0 0
Clearance (CL) as Measured by the aPTT Clotting Assay
Timepoint [3] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [4] 0 0
Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay
Timepoint [4] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [5] 0 0
Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay
Timepoint [5] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [6] 0 0
Time of Cmax (Tmax) as Measured by aPTT Clotting Assay
Timepoint [6] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [7] 0 0
Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay
Timepoint [7] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [8] 0 0
Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay
Timepoint [8] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [9] 0 0
Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay
Timepoint [9] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [10] 0 0
Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay
Timepoint [10] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [11] 0 0
Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT
Timepoint [11] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [12] 0 0
AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [12] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [13] 0 0
IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [13] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [14] 0 0
Cmax as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [14] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [15] 0 0
t½ as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [15] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [16] 0 0
CL as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [16] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [17] 0 0
Vss as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [17] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [18] 0 0
MRT as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [18] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [19] 0 0
Tmax as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [19] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [20] 0 0
AUClast as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [20] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [21] 0 0
Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [21] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [22] 0 0
AUCext as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [22] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [23] 0 0
DNAUC as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [23] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [24] 0 0
Vz as Measured by Two-Stage Chromogenic Clotting Assay
Timepoint [24] 0 0
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Secondary outcome [25] 0 0
Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay
Timepoint [25] 0 0
Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only)

Eligibility
Key inclusion criteria
Key

* Have severe hemophilia A
* Previously treated subject, defined as having at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc- study drug or commercial product) at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
* No history of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude subjects.
* No measurable inhibitor activity using the Nijmegen-modified Bethesda assay at Screening.
* Platelet count =100,000 platelets/µL at screening
* CD4 lymphocytes >200 mm3 if known as HIV antibody positive at screening.
* Viral load of <400 copies/mL if known HIV antibody positive at screening.

Key
Minimum age
12 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion.
* Previous treatment with rFVIIIFc as study drug or commercial product.
* Other coagulation disorder(s) in addition to hemophilia A.
* History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
* Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other nonsteroidal anti-inflammatory drugs are permitted).
* Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Day 1. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days at a dose of =1 mg/kg within 12 weeks prior to Day 1) and/or inhaled steroids.

NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2015
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Herston
Recruitment hospital [2] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
- Herston
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Utah
Country [3] 0 0
United States of America
State/province [3] 0 0
Washington
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Basingstoke
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Cambridge
Country [6] 0 0
United Kingdom
State/province [6] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bioverativ Therapeutics Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to characterize the pharmacokinetics (PK) of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A. The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months for a continued treatment period.
Trial website
https://clinicaltrials.gov/study/NCT02083965
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Bioverativ Therapeutics Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02083965