A Safety and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor VIIa With Albumin (rVIIa-FP) in Healthy Male Volunteers

A Randomized, Placebo-controlled, Single Center, 5 Cohort Dose Escalation Trial to Investigate Safety and Pharmacokinetics of rVIIa-FP (CSL689) in Comparison to Placebo in Healthy Male Human Volunteers

This is a first in man, prospective, single-center, randomized, double-blind, dose-escalation cohort study to investigate tolerability, safety and pharmacokinetics of rVIIa-FP in comparison to placebo.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: rVIIa-FP; Biological: Placebo (0.9% normal saline)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Phase I Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects between 18 and 35 years of age, both inclusive.
• Body weight between 50.0 and 100.0 kg, both inclusive.
• Body mass index (BMI) between 18.0 and 29.9 kg/m2, both inclusive.
• Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

• Subjects at increased cardiovascular risk.
• Any clinical sign or known history of atherosclerosis or thromboembolic events.
• A subject considered at high risk of thromboembolic events confirmed either from history or by thrombophilia screening test.
• Subjects with significant elevation of cholesterol level.
• Renal dysfunction.
• Overt bleeding.
• Smokers with positive cotinine test at screening.
• Participation in any other trial investigating a procoagulant within the last six months prior to screening.
• Known or suspected hypersensitivity to the investigational medicinal product (IMP), or to any excipients of the IMP.
• Contraindications to Warfarin (Coumadin®).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rVIIa-FP	Biological: rVIIa-FP; Recombinant VIIa-FP (rVIIa-FP) is a fusion protein linking coagulation factor VIIa with albumin and will be administered by intravenous infusion in escalating doses up to 1000 mcg/kg. Participants will receive pre-treatment with an oral anticoagulant starting 7 days prior to administration of study product and continuing for 7 days after study product has been administered.
Placebo Comparator: Placebo (0.9% normal saline)	Biological: Placebo (0.9% normal saline); Placebo will be administered by intravenous infusion. Participants will receive pre-treatment with an oral anticoagulant starting 7 days prior to administration of placebo and continuing for 7 days after placebo has been administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The frequency of related Adverse Events (AEs) to rVIIa-FP.	28 days
Number of subjects who develop inhibitors against Factor VII (FVII).	28 days
Number of subjects who develop antibodies against rVIIa-FP.	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under curve to the last sample with quantifiable drug concentration (AUC0-t) of a single dose of rVIIa-FP	120 hours
Half- life (t1/2) of a single dose of rVIIa-FP	120 hours
Incremental recovery (IR) of rVIIa-FP	120 hours
Clearance (Cl) of a single dose of rVIIa-FP	120 hours

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Alex Veldman, M.D., CSL Behring

Publications and helpful links

General Publications

• Golor G, Bensen-Kennedy D, Haffner S, Easton R, Jung K, Moises T, Lawo JP, Joch C, Veldman A. Safety and pharmacokinetics of a recombinant fusion protein linking coagulation factor VIIa with albumin in healthy volunteers. J Thromb Haemost. 2013 Nov;11(11):1977-85. doi: 10.1111/jth.12409.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: February 26, 2012
• First Submitted That Met QC Criteria: February 26, 2012
• First Posted (Estimate): March 2, 2012

Study Record Updates

• Last Update Posted (Actual): April 21, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Other Study ID Numbers: CSL689_1001; 2011-004568-32 (EudraCT Number)