Overview

This trial has been completed.

Condition congenital coagulation factor vii deficiency
Treatments eptacog alfa (activated) or pdfvii, csl689
Phase phase 1
Sponsor CSL Behring
Start date July 2015
End date July 2016
Trial size 9 participants
Trial identifier NCT02470871, CSL689_1002

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Arm
(Experimental)
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
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.
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)
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
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
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 Outcomes

Measure
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

Secondary Outcomes

Measure
Total clearance
time frame: Before injection and at up to 9 time points until 48 hours after injection
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
Incremental recovery
time frame: Before injection and at up to 9 time points until 48 hours after injection
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

Eligibility Criteria

Male or female participants at least 18 years old.

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])

Additional Information

Official title Multi-center, Randomized, Open-label, Parallel-Arm, Single-dose, Pharmacokinetic Study of rVIIa-FP (CSL689) in Subjects With Congenital Factor VII Deficiency
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by CSL Behring.