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

NCT02470871 | Completed Phase 1

• 2 other identifiers: CSL689_10022014-002982-32
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 2

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• Total clearance

  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)

  Before injection and at up to 9 time points until 48 hours after injection

• Incremental recovery

  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

Study Arms (2)

Low-dose CSL689

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

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

High-dose CSL689

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.

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

Interventions

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.

High-dose CSL689; Low-dose CSL689

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)

High-dose CSL689; Low-dose CSL689

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[eg, for oral bleeds\])

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (2)

Site Reference 5280023

Njmegen, 6500, Netherlands

Location

Site Reference # 5780001

Oslo, 0372, Norway

Location

MeSH Terms

Interventions

recombinant FVIIa

Study Officials

• Alex Veldman

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 12, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: October 1, 2016
• Last Updated: April 26, 2017

Record last verified: 2016-11

Locations

NL (1); NO (1)