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Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency

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ClinicalTrials.gov Identifier: NCT02470871
Recruitment Status : Completed
First Posted : June 12, 2015
Last Update Posted : April 26, 2017
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Tracking Information
First Submitted Date  ICMJE June 10, 2015
First Posted Date  ICMJE June 12, 2015
Last Update Posted Date April 26, 2017
Study Start Date  ICMJE July 2015
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • Terminal half-life of plasma FVIIa activity [ Time Frame: Up to 48 hours after CSL689 injection ]
  • Maximum observed plasma FVIIa activity [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
  • Area under the curve (AUC0-t) [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
    Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02470871 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • Total clearance [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
    Total clearance of plasma FVIIa activity
  • Volume of distribution of the terminal phase [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
  • AUC(0-inf) [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
    Area under plasma FVIIa activity versus time curve from time 0 extrapolated to infinity
  • Incremental recovery [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
    Incremental recovery of plasma FVIIa activity
  • 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 ]
  • Number of subjects with antibodies against Chinese hamster ovary protein and FVII [ Time Frame: Up to 30 days after CSL689 injection ]
  • Number of subjects with inhibitors against FVII [ Time Frame: Up to 30 days after CSL689 injection ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Pharmacokinetics and Safety of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) in Patients With Congenital Factor VII Deficiency
Official Title  ICMJE Multi-center, Randomized, Open-label, Parallel-Arm, Single-dose, Pharmacokinetic Study of rVIIa-FP (CSL689) in Subjects With Congenital Factor VII Deficiency
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Congenital Coagulation Factor VII Deficiency
Intervention  ICMJE
  • Biological: Eptacog alfa (activated) or pdFVII

    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.

  • Biological: CSL689
    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)
Study Arms  ICMJE
  • Experimental: Low-dose CSL689
    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
    Interventions:
    • Biological: Eptacog alfa (activated) or pdFVII
    • Biological: CSL689
  • Experimental: High-dose CSL689
    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.
    Interventions:
    • Biological: Eptacog alfa (activated) or pdFVII
    • Biological: CSL689
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2016)
9
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2015)
16
Actual Study Completion Date  ICMJE October 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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])
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands,   Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02470871
Other Study ID Numbers  ICMJE CSL689_1002
2014-002982-32 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alex Veldman CSL Behring
PRS Account CSL Behring
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP