Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency
Primary Purpose
Congenital Coagulation Factor VII Deficiency
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Eptacog alfa (activated) or pdFVII
CSL689
Sponsored by
About this trial
This is an interventional other trial for Congenital Coagulation Factor VII Deficiency
Eligibility Criteria
Inclusion Criteria:
- Proven congenital FVII deficiency.
- Age ≥ 18 years.
- FVII level < 2% of normal levels.
- Minimum of 50 previous exposure days to pdFVII (including prothrombin complex concentrates [PCCs]) or rFVIIa.
Exclusion Criteria:
- History of, or risk factors for, thromboembolic events, including known deep vein thrombosis.
- Inhibitor to FVII or rFVIIa, current or historic.
- Known or suspected hypersensitivity to hamster protein, to CSL689, or to any excipient of CSL689.
- Known or suspected allergy to rFVIIa or hamster protein.
- Major surgery within 1 month before screening.
- Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke).
- Human immunodeficiency virus (HIV)-positive subjects with cluster of differentiation 4 (CD4)+ lymphocyte count of < 200/µL at screening.
- Use of an investigational agent within 30 days before the study.
- Use of concomitant therapy not permitted during the study (ie, other platelet inhibitors, desmopressin, fibrinolysis inhibitors, except if used as local treatment [eg, for oral bleeds])
Sites / Locations
- Site Reference 5280023
- Site Reference # 5780001
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Low-dose CSL689
High-dose CSL689
Arm Description
Single dose of subject's routine FVII replacement therapy (either eptacog alfa [activated] [ie, comparator drug 1] or pdFVII [ie, comparator drug 2]), followed by a single dose of CSL689 at the low dose
Single dose of subject's routine FVII replacement therapy (either eptacog alfa [activated] [ie, comparator drug 1] or pdFVII [ie, comparator drug 2]), followed by a single dose of CSL689 at the high dose.
Outcomes
Primary Outcome Measures
Terminal half-life of plasma FVIIa activity
Maximum observed plasma FVIIa activity
Area under the curve (AUC0-t)
Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity
Secondary Outcome Measures
Total clearance
Total clearance of plasma FVIIa activity
Volume of distribution of the terminal phase
AUC(0-inf)
Area under plasma FVIIa activity versus time curve from time 0 extrapolated to infinity
Incremental recovery
Incremental recovery of plasma FVIIa activity
Time of occurrence of maximum observed plasma FVIIa activity
Number of subjects with antibodies against Chinese hamster ovary protein and FVII
Number of subjects with inhibitors against FVII
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02470871
Brief Title
Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency
Official Title
Multi-center, Randomized, Open-label, Parallel-Arm, Single-dose, Pharmacokinetic Study of rVIIa-FP (CSL689) in Subjects With Congenital Factor VII Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
October 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to investigate the pharmacokinetics (PK) and safety of rVIIa-FP (CSL689) in a total of 10 to 16 male or female adults with inherited coagulation factor VII (FVII) deficiency. Subjects will receive a single dose of their routine FVII replacement product (ie, either recombinant activated coagulation FVII [rFVIIa, eptacog alfa (activated)] or plasma-derived FVII [pdFVII]) as a comparator, and will then be randomly assigned to a single low dose or a single high dose of the study product CSL689 (8 subjects per CSL689 dose level). Serial blood samples for PK analysis will be taken up to 24 hours after the eptacog alfa (activated) or pdFVII injection, and up to 48 hours after the CSL689 injection. Subject safety will be routinely monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Coagulation Factor VII Deficiency
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low-dose CSL689
Arm Type
Experimental
Arm Description
Single dose of subject's routine FVII replacement therapy (either eptacog alfa [activated] [ie, comparator drug 1] or pdFVII [ie, comparator drug 2]), followed by a single dose of CSL689 at the low dose
Arm Title
High-dose CSL689
Arm Type
Experimental
Arm Description
Single dose of subject's routine FVII replacement therapy (either eptacog alfa [activated] [ie, comparator drug 1] or pdFVII [ie, comparator drug 2]), followed by a single dose of CSL689 at the high dose.
Intervention Type
Biological
Intervention Name(s)
Eptacog alfa (activated) or pdFVII
Intervention Description
Comparator Drug 1: Recombinant activated FVII (rFVIIa). Subjects with eptacog alfa (activated) as their routine FVII replacement therapy will receive a single dose of eptacog alfa (activated) in the study.
Comparator Drug 2: Plasma-derived FVII (pdFVII). Subjects with pdFVII as their routine FVII replacement therapy will receive a single injection of pdFVII in the study.
Intervention Type
Biological
Intervention Name(s)
CSL689
Intervention Description
Experimental Drug: Recombinant fusion protein, linking activated FVII with albumin (rVIIa-FP). Subjects will receive a single dose of CSL689 at either a low dose (Arm 1) or a high dose (Arm 2)
Primary Outcome Measure Information:
Title
Terminal half-life of plasma FVIIa activity
Time Frame
Up to 48 hours after CSL689 injection
Title
Maximum observed plasma FVIIa activity
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Title
Area under the curve (AUC0-t)
Description
Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Secondary Outcome Measure Information:
Title
Total clearance
Description
Total clearance of plasma FVIIa activity
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Title
Volume of distribution of the terminal phase
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Title
AUC(0-inf)
Description
Area under plasma FVIIa activity versus time curve from time 0 extrapolated to infinity
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Title
Incremental recovery
Description
Incremental recovery of plasma FVIIa activity
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Title
Time of occurrence of maximum observed plasma FVIIa activity
Time Frame
Before injection and at up to 9 time points until 48 hours after injection
Title
Number of subjects with antibodies against Chinese hamster ovary protein and FVII
Time Frame
Up to 30 days after CSL689 injection
Title
Number of subjects with inhibitors against FVII
Time Frame
Up to 30 days after CSL689 injection
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Proven congenital FVII deficiency.
Age ≥ 18 years.
FVII level < 2% of normal levels.
Minimum of 50 previous exposure days to pdFVII (including prothrombin complex concentrates [PCCs]) or rFVIIa.
Exclusion Criteria:
History of, or risk factors for, thromboembolic events, including known deep vein thrombosis.
Inhibitor to FVII or rFVIIa, current or historic.
Known or suspected hypersensitivity to hamster protein, to CSL689, or to any excipient of CSL689.
Known or suspected allergy to rFVIIa or hamster protein.
Major surgery within 1 month before screening.
Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke).
Human immunodeficiency virus (HIV)-positive subjects with cluster of differentiation 4 (CD4)+ lymphocyte count of < 200/µL at screening.
Use of an investigational agent within 30 days before the study.
Use of concomitant therapy not permitted during the study (ie, other platelet inhibitors, desmopressin, fibrinolysis inhibitors, except if used as local treatment [eg, for oral bleeds])
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alex Veldman
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference 5280023
City
Njmegen
ZIP/Postal Code
6500
Country
Netherlands
Facility Name
Site Reference # 5780001
City
Oslo
ZIP/Postal Code
0372
Country
Norway
12. IPD Sharing Statement
Learn more about this trial
Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency
We'll reach out to this number within 24 hrs