A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Bendavia™ (MTP-131) in Patients With Heart Failure

Study Overview
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Brief Summary
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This study is a single-center, randomized, double-blind, placebo-controlled study in patients with stable heart failure to evaluate the safety, tolerability, pharmacokinetics, and efficacy of multiple ascending doses of Bendavia™ (MTP-131) intravenous infusion.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Bendavia™ (MTP-131) in Patients With Heart Failure Due to Reduced Left Ventricular Ejection Fraction

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: MTP-131
* Drug: MTP-131
* Drug: MTP-131
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LVEF ≤45% by 2-D echocardiogram. Diagnosis of New York Heart Association Class II or III HF for a minimum of 6 months prior to the Screening Visit. HF is considered to be stable, in the judgment of the Principal Investigator and no hospitalization related to HF has occurred within the 1 month prior to the Screening Visit. Treatment with appropriate pharmacologic therapy for HF including, but not limited to, angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB), and an evidence-based beta blocker for the treatment of HF Females of child-bearing potential must have a negative serum pregnancy test at the Screening Visit. Written informed consent obtained that strictly adheres to the written guidelines from the local Ethical Committee (EC). Exclusion Criteria: Unstable angina pectoris within 1 month before initiation of screening procedures. Unstable angina is defined as the occurrence of chest pain more frequently than usual, pain at rest or upon minimal exertion, or protracted episodes of pain without any discernible trigger, and/or chest pain that persists despite use of vasodilatory therapy (e.g., nitroglycerin). Coronary or peripheral artery revascularization procedure within 2 months prior to the Screening Visit. An acute myocardial infarction within 3 months prior to the Screening Visit. Supine resting heart rate ≥ 100 beats per minute after 5 minutes rest. Uncontrolled hypertension defined as a systolic blood pressure (BP) >180 mm Hg or a diastolic BP >110 mm Hg on at least 2 consecutive readings. Requirement for valve or other cardiac surgery (e.g., pericardectomy). Cardiac surgery or valvuloplasty within 2 month prior to the Screening Visit. General surgery within 1 month prior to the Screening Visit. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic left ventricular aneurysm. Cerebrovascular accident or transient ischemic attack within 3 months prior to the Screening Visit. Liver enzyme (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) elevation >3x the upper limit of normal (ULN). Estimated glomerular filtration rate (eGFR) <30 mL/min, using the Modification of Diet in Renal Disease (MDRD) Study equation. Known active drug or alcohol abuse. Active infection requiring systemic treatment or surgical intervention. Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study. Female patients who are pregnant or breastfeeding. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br> | Drug: MTP-131<br>* MTP-131 (low dose) administered as once-daily 1- hour intravenous infusion for 5 consecutive days<br>|
| Experimental: Intermediate dose<br> | Drug: MTP-131<br>* MTP-131 (intermediate dose) administered as once-daily 1- hour intravenous infusion for 5 consecutive days<br>|
| Experimental: High dose<br> | Drug: MTP-131<br>* MTP-131 (high dose) administered as once-daily 1- hour intravenous infusion for 5 consecutive days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo Comparator (at each dose cohort) administered as once-daily 1- hour intravenous infusion for 5 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events |  | Assessed up to Day 33 | 
| Mean peak plasma concentration (Cmax) of MTP-131 (ng/ml) in each cohort |  | Assessed up to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in echocardiographic LV end-systolic volume (LVESV) |  | Assessed up to Day 33 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Bendavia™, MTP-131