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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Biological: rVIIa-FP
* Biological: Placebo (0.9% normal saline)


Participation Criteria
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Eligibility Criteria
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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®).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rVIIa-FP<br> | Biological: rVIIa-FP<br>* 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.<br>|
| Placebo Comparator: Placebo (0.9% normal saline)<br> | Biological: Placebo (0.9% normal saline)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |