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

Phase 1

Completed

• Conditions: Congenital Coagulation Factor VII Deficiency
• Interventions: Biological: Eptacog alfa (activated) or pdFVII; Biological: CSL689

• Registration Number: NCT02470871
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-10
• Study First Submitted QC: 2015-06-10
• Study First Posted: 2015-06-12
• Study Start: 2015-07
• Primary Completion: 2016-07
• Study Completion: 2016-10
• Status Verified: 2016-11
• Last Update Submitted: 2017-04-25
• Last Update Posted: 2017-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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.

Read More

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])

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose CSL689	Eptacog alfa (activated) or pdFVII	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
Low-dose CSL689	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	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.
High-dose CSL689	Eptacog alfa (activated) or pdFVII	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of subjects with antibodies against Chinese hamster ovary protein and FVII	Up to 30 days after CSL689 injection
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
Number of subjects with inhibitors against FVII	Up to 30 days after CSL689 injection
Time of occurrence of maximum observed plasma FVIIa activity	Before injection and at up to 9 time points until 48 hours after injection

Trial Locations

Locations (2)

Site Reference # 5780001; 🇳🇴 Oslo, Norway

Site Reference 5280023; 🇳🇱 Njmegen, Netherlands