Efficacy and Safety of OPL-0301 Compared to Placebo in Adults With Post-Myocardial Infarction (MI)

Study Overview
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Brief Summary
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Study OPL-0301-201 is intended to generate efficacy and safety data of OPL-0301 in participants with post-myocardial infarction (MI) left ventricular dysfunction (LVD)

Detailed Description
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OPL-0301 is intended to address the disease state of post-myocardial infarction (MI) left ventricular dysfunction (LVD). MI is a manifestation of atherosclerotic coronary artery disease, the pathogenesis of which is closely associated with vascular and endothelial dysfunction, and inflammation. Acute MI leads to acute LVD, which often persists, leading to poor cardiovascular outcomes. The therapeutic hypothesis is that these effects mediated by Sphingosine-1 Phosphate 1 (S1P1) receptor agonism with OPL-0301 will reduce infarct size and benefit post-MI left ventricular function, thereby supporting improved cardiovascular outcomes in this patient population.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Multiple-arm, Parallel-group, Adaptive Study to Investigate the Efficacy and Safety of OPL-0301 in Patients With Post-myocardial Infarction Left Ventricular Dysfunction (RESTORE)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: OPL-0301 Dose 1
* Drug: OPL-0301 Dose 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are male or female between 18 and 90 years of age, inclusive, at the time of signing the informed consent Are hospitalized with acute ST-Elevated Myocardial Infarction (STEMI), defined based on American Heart Association (AHA)/American College of Cardiology (ACC) criteria Have cardiac troponin-I (cTnI), cardiac troponin-T (cTnT) levels ≥10x upper limit of normal (ULN) at least once during the index event of myocardial infarction Exclusion Criteria: Previous history of documented myocardial infarction Previous history of percutaneous coronary intervention (PCI) within 6 months or coronary artery bypass graft surgery (CABG) or valvular heart surgery at any time prior to screening Previous history of documented chronic left ventricular dysfunction with ejection fraction (EF) < 50% Previous history of decompensated heart failure Previous history of documented specific cardiomyopathy (including but not limited to hypertrophic cardiomyopathy (HCM), amyloid, sarcoid, etc.) Previous history of documented arrhythmias Are being treated with Sphingosine-1 Phosphate (S1P) modulators (fingolimod, siponimod, ozanimod, ponesimod)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 2, multicenter, randomized, placebo-controlled, multiple-arm, adaptive study investigating the safety, pharmacokinetics, and potential efficacy of OPL-0301, along with standard of care, in post-myocardial infarction (MI) participants with left ventricular dysfunction (LVD). Participants will have been admitted to the hospital for acute MI and treated with primary percutaneous coronary intervention (PPCI) before entering the study. A fixed oral dose will be administered once daily, according to the blinded treatment assignment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPL-0301 Dose 1<br>Participants are randomized to OPL-0301 Dose 1 administered once daily for 90 days | Drug: OPL-0301 Dose 1<br>* Pharmaceutical form: Hard gelatin capsule; Route of administration: Oral<br>|
| Experimental: OPL-0301 Dose 2<br>Participants are randomized to OPL-0301 Dose 2 administered once daily for 90 days | Drug: OPL-0301 Dose 2<br>* Pharmaceutical form: Hard gelatin capsule; Route of administration: Oral<br>|
| Placebo Comparator: Placebo<br>Participants are randomized to matching placebo administered once daily for 90 days | Drug: Placebo<br>* Pharmaceutical form: Hard gelatin capsule; Route of administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct size as determined by cardiac magnetic resonance (CMR) at Day 90 | To evaluate the effects of OPL-0301 versus placebo on infarct size in adults with post-myocardial infarction left ventricular dysfunction at day 90 | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in infarct size by cardiac magnetic resonance (CMR) from initial CMR assessment to Day 90 | To evaluate the effects of OPL-0301 versus placebo on the change in infarct size in adults with post-myocardial infarction left ventricular dysfunction | Initial to 90 days | 
| Adverse events (AEs) and Serious adverse events (SAEs) | To assess the effects of OPL-0301 on safety and tolerability | Baseline to 120 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart attack, acute ischemic heart disease, acute coronary syndrome, ST-Elevated Myocardial Infarction, left ventricular dysfunction