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

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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Coagulation Factor VII Deficiency
• Intervention / Treatment: Biological: Eptacog alfa (activated) or pdFVII; Biological: CSL689

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Njmegen, Netherlands, 6500
    • Site Reference 5280023
• Norway
  • Oslo, Norway, 0372
    • Site Reference # 5780001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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])

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Area under plasma FVIIa activity versus time curve from time 0 to last sample with quantifiable activity	Before injection and at up to 9 time points until 48 hours after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total clearance	Total clearance of plasma FVIIa activity	Before injection and at up to 9 time points until 48 hours after injection
Volume of distribution of the terminal phase		Before injection and at up to 9 time points until 48 hours after injection
AUC(0-inf)	Area under plasma FVIIa activity versus time curve from time 0 extrapolated to infinity	Before injection and at up to 9 time points until 48 hours after injection
Incremental recovery	Incremental recovery of plasma FVIIa activity	Before injection and at up to 9 time points until 48 hours after injection
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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Alex Veldman, CSL Behring

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 10, 2015
• First Posted (Estimate): June 12, 2015

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Factor VII Deficiency
• Other Study ID Numbers: CSL689_1002; 2014-002982-32 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No