Study to Assess the Safety and Efficacy of SelK2 to Prevent Blood Clots in Patients Undergoing Total Knee Replacement

Study Overview
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Brief Summary
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The main purpose of this study is to determine if an investigational medication called SelK2 works in preventing a condition called venous thromboembolism (VTE) in patients having a total knee replacement. SelK2 has been designed to attach to a protein found on blood cells and blood vessels. By attaching to this protein, SelK2 is designed to decrease the inflammatory process in the blood vessel wall that leads to the formation of blood clots in the vessel (called thrombosis). By decreasing the inflammatory process, SelK2 may reduce the risk of VTE following joint replacement surgery. In addition, because SelK2 is not a blood thinner, it is expected that the risk for bleeding will also be reduced.

Official Title
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A Phase 2, Randomized, Active Comparator-Controlled, Open-Label, Adaptive Design Study to Assess the Safety and Efficacy of Intravenously-Administered SelK2 in Patients Undergoing Total Knee Arthroplasty

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: SelK2
* Biological: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males or females, 18-80 years of age (inclusive) Planned to undergo elective, primary total unilateral Total Knee Arthroplasty under general anesthesia Key Exclusion Criteria: Previous deep vein thrombosis (DVT) of the leg or pulmonary embolism (PE) within the past year Any underlying condition (e.g., atrial fibrillation, mechanical heart valve, or recent pulmonary embolism) that may lead to the required concomitant use of anticoagulants/antiplatelet agents (e.g., warfarin, dabigatran, rivaroxaban, apixaban, clopidogrel) that may affect study outcome or any other drug influencing coagulation (except low dose aspirin (100 mg or less)) Anticipated use of intermittent pneumatic compression devices and/or electrical/mechanical muscle stimulators post Total Knee Arthroplasty procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This was an adaptive design study. The first two arms of the study enrolled patients in a 1:1 ratio to receive either SelK2 or an active comparator. The adaptive arm (SelK2 plus active comparator) was initiated at the discretion of the Steering and Safety Committee. The study then enrolled patients in a 2:1 ratio to receive either SelK2 with an active comparator or an active comparator only.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SelK2 and Enoxaparin<br>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin) | Drug: SelK2<br>* I.V., single-dose<br>Biological: Enoxaparin<br>* SC, QD for up to 10 ± 2 days<br>* Other names: Lovenox;|
| Active Comparator: Enoxaparin<br>SC, QD for up to 10 ± 2 days | Biological: Enoxaparin<br>* SC, QD for up to 10 ± 2 days<br>* Other names: Lovenox;|
| Experimental: SelK2<br>I.V., single-dose | Drug: SelK2<br>* I.V., single-dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Total Venous Thromboembolism | The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC). | 10 ± 2 Days After Total Knee Replacement | 
| Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events | All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB. | 10 ± 2 Days After Total Knee Replacement | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venous thromboembolism, adhesion molecule, P-selectin glycoprotein ligand 1, P-selectin, venous thrombosis