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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

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.

Condition or disease Intervention/treatment Phase
Congenital Coagulation Factor VII Deficiency Biological: Eptacog alfa (activated) or pdFVII Biological: CSL689 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
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 Start Date : July 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : October 2016


Arm Intervention/treatment
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
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)

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.
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)




Primary Outcome Measures :
  1. Terminal half-life of plasma FVIIa activity [ Time Frame: Up to 48 hours after CSL689 injection ]
  2. Maximum observed plasma FVIIa activity [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
  3. 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


Secondary Outcome Measures :
  1. Total clearance [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
    Total clearance of plasma FVIIa activity

  2. Volume of distribution of the terminal phase [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
  3. 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

  4. Incremental recovery [ Time Frame: Before injection and at up to 9 time points until 48 hours after injection ]
    Incremental recovery of plasma FVIIa activity

  5. 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 ]
  6. Number of subjects with antibodies against Chinese hamster ovary protein and FVII [ Time Frame: Up to 30 days after CSL689 injection ]
  7. Number of subjects with inhibitors against FVII [ Time Frame: Up to 30 days after CSL689 injection ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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])

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02470871


Locations
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Netherlands
Site Reference 5280023
Njmegen, Netherlands, 6500
Norway
Site Reference # 5780001
Oslo, Norway, 0372
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Alex Veldman CSL Behring

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02470871     History of Changes
Other Study ID Numbers: CSL689_1002
2014-002982-32 ( EudraCT Number )
First Posted: June 12, 2015    Key Record Dates
Last Update Posted: April 26, 2017
Last Verified: November 2016

Additional relevant MeSH terms:
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Factor VII Deficiency
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn