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

NCT02470871 — Phase 1, Completed, 9 participants, CSL Behring

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Multi-center, Randomized, Open-label, Parallel-Arm, Single-dose, Pharmacokinetic Study of rVIIa-FP (CSL689) in Subjects With Congenital Factor VII Deficiency

Registry	NCT02470871
Status	Completed
Phase	Phase 1
Study type	Interventional; randomized, parallel, masking: none, other
Enrollment	9 (Actual)
Sponsor	CSL Behring (Industry)
Conditions	Congenital Coagulation Factor VII Deficiency
Interventions	Eptacog alfa (activated) or pdFVII, CSL689 (Biological)
Dates	start 2015-07-01, primary completion 2016-07-01, completion 2016-10-01, first posted 2015-06-12, last updated 2017-04-26
Locations	2 sites in Netherlands, Norway

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Low-dose CSL689	Experimental	Biological: Eptacog alfa (activated) or pdFVII; Biological: 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
High-dose CSL689	Experimental	Biological: Eptacog alfa (activated) or pdFVII; Biological: 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.

Eptacog alfa (activated) or pdFVII (Biological): 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.
CSL689 (Biological): 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)

+Outcome measures

Primary outcomes

Terminal half-life of plasma FVIIa activity [Up to 48 hours after CSL689 injection]
Maximum observed plasma FVIIa activity [Before injection and at up to 9 time points until 48 hours after injection]
Area under the curve (AUC0-t) [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 outcomes

Total clearance [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 [Before injection and at up to 9 time points until 48 hours after injection]
AUC(0-inf) [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 [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 [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 [Up to 30 days after CSL689 injection]
Number of subjects with inhibitors against FVII [Up to 30 days after CSL689 injection]

+Eligibility

Sex: All, ages: 18 Years to any

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 \[eg, for oral bleeds\])

+Locations (2)

Facility	City	Country	Status
Site Reference 5280023	Njmegen	Netherlands
Site Reference # 5780001	Oslo	Norway

+Investigators

Alex Veldman, Study director, CSL Behring

+Funding

NIH grants: 2014