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

NCT ID: NCT02470871

Last Updated: 2017-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2016-10-31

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.

Conditions

Congenital Coagulation Factor VII Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Eptacog alfa (activated) or pdFVII

Intervention Type: 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

Intervention Type: 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)

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.

Group Type: EXPERIMENTAL

Eptacog alfa (activated) or pdFVII

Intervention Type: 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

Intervention Type: 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)

Interventions

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.

Intervention Type: 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)

Intervention Type: BIOLOGICAL

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])

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Veldman

Role: STUDY_DIRECTOR

CSL Behring

Locations

Site Reference 5280023

Njmegen, , Netherlands

Site Reference # 5780001

Oslo, , Norway

Countries

Netherlands; Norway

Other Identifiers

2014-002982-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSL689_1002

Identifier Type: -

Identifier Source: org_study_id