Dose-Response in PD and Safety of Cofact Under VKA Anticoagulation

Study Overview
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Brief Summary
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This is a randomized, open label, placebo-controlled, parallel design, single center, prospective study. Subjects will receive treatment with VKA. Subjects who reach the targeted INR, will receive single dose of Cofact. Multiple coagulation laboratory tests will be evaluated over a period of 15 days

Official Title
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A Phase 1/2 Study of the Dose-Response in Pharmacodynamics and Safety of Prothrombin Complex Concentrate Cofact in Healthy Subjects Under Vitamin K Antagonist Anticoagulation.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Cofact


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of nonchildbearing potential. Healthy subjects. Exclusion Criteria: Evidence of coagulation disturbances, or disposition for thrombo-embolic events Liver function tests more than 1.2 times the upper normal limits Participants with thyroid disorders as evidenced by assessment of TSH levels outside the normal reference range at screening. Prior history of thromboembolic complications including those in first degree relatives. Glomerular filtration rate (GFR) is lower than estimated GFR 62 mL/min/1.73 m2 using the Modification of Diet in Renal Disease Study equation. Anaphylactic or systemic reactions to human plasma, plasma products, or blood products. History of hypersensitivity to active or inactive excipients of VKA Gastrointestinal disease that may impair VKA absorption.. Participation in another clinical study <30 days prior to study entry. Any clinically significant history of or current clinically significant disease or disorder as judged by the Investigator. Positive nasopharyngeal PCR test for SARS-CoV-2 on Day -11 or Day -1. Positive pregnancy test at screening, Day -11, or Day -1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cofact Dose 1<br> | Biological: Cofact<br>* Human prothrombin complex concentrate<br>|
| Experimental: Cofact Dose 2<br> | Biological: Cofact<br>* Human prothrombin complex concentrate<br>|
| Placebo Comparator: Placebo<br> | Biological: Cofact<br>* Human prothrombin complex concentrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak thrombin generation at 30 minutes after end of the Cofact infusion |  | 30 minutes post Cofact infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ETP | Change in endogenous thrombin potential (ETP) over 24 hours after the EOI | 24 hours post Cofact infusion | 
| Concentration in clotting factors | Changes in aPTT, PT, and INR | up to Day 15 | 
| Coagulation markers | Concentration over time of clotting factors: FII, FVII, FIX, FX, protein C, and protein S | up to Day 15 | 
| Coagulation activation markers | Concentration over time of Prothrombin fragment 1+2, D-dimer, and thrombin-antithrombin complexes (TATs) | up to Day 15 | 
| Safety outcome | Frequency and severity of adverse events (AEs) | up to Day 15 |