A Study Investigating the Safety, Tolerability, and Pharmacokinetics of MTP-131 in Subjects With Congestive Heart Failure

A Phase 1 Clinical Pharmacology Study of the Effects of a Single 4 Hour Intravenous Infusion of Bendavia™ (MTP-131) in Subjects With Stable New York Heart Association Class II-III Congestive Heart Failure Due to Left Ventricular Systolic Dysfunction

This is a Phase 1, single-center, randomized, double-blind, single ascending dose, placebo-controlled study, in subjects aged 45-80 years with stable mild to moderate heart failure due to left ventricular systolic dysfunction, to evaluate the safety, tolerability, and pharmacokinetics of escalating single intravenous infusion doses of Bendavia™ (MTP-131).

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Drug: MTP-131; Drug: MTP-131; Drug: MTP-131; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Gabrovo
    • Sevlievo, Gabrovo, Bulgaria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic ischemic or non-ischemic cardiomyopathy of at least 6 months duration from the time of the initial diagnosis.
• LVEF ≤35% by 2-D echocardiogram.
• Diagnosis of NYHA Class II or III HF for a minimum of 6 months prior to the Screening Visit.
• HF is considered to be stable and no hospitalization for HF has occurred within the previous 3 months 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 (i.e. carvedilol, bisoprolol, or extended-release metoprolol).
• Dose and dose regimen of pharmacologic treatments for HF must be stable for a minimum of 1 month prior to the Screening Visit.
• Females of child-bearing potential must have a negative serum pregnancy test at the Screening Visit and Day 1.

Exclusion Criteria:

• LV end-diastolic dimension (LVEDD), by the same method as qualifying LVEF, is >80 mm or LVEDD indexed to body surface area is >0.45.
• 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.
• Placement of an automated implantable cardioverter defibrillator (AICD) or any hardware associated with resynchronization therapy.
• Atrial fibrillation at the Screening or Baseline Visits.
• 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
• Cardiac surgery or valvuloplasty within 2 months 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.
• Estimated glomerular filtration rate (eGFR) <40 mL/min, using the Modification of Diet in Renal Disease (MDRD) Study equation
• Serologic evidence of hepatitis B or C infection.

• Known acquired immunodeficiency syndrome or HIV-positive status, or diagnosis of immunodeficiency.

  • Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Drug: Placebo; Placebo Comparator (at each dose cohort) administered as single intravenous infusion over 4 hours
Experimental: Low dose	Drug: MTP-131; MTP-131 (low dose) administered as single intravenous infusion over 4 hours; Drug: MTP-131; MTP-131 (intermediate dose) administered as single intravenous infusion over 4 hours; Drug: MTP-131; MTP-131 (high dose) administered as single intravenous infusion over 4 hours
Experimental: High dose	Drug: MTP-131; MTP-131 (low dose) administered as single intravenous infusion over 4 hours; Drug: MTP-131; MTP-131 (intermediate dose) administered as single intravenous infusion over 4 hours; Drug: MTP-131; MTP-131 (high dose) administered as single intravenous infusion over 4 hours
Experimental: Intermediate dose	Drug: MTP-131; MTP-131 (low dose) administered as single intravenous infusion over 4 hours; Drug: MTP-131; MTP-131 (intermediate dose) administered as single intravenous infusion over 4 hours; Drug: MTP-131; MTP-131 (high dose) administered as single intravenous infusion over 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events	Assessed up to Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Left ventricular ejection fraction assessed by 2-D echocardiography	Assessed up to 24 hours post-infusion start

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.

Publications and helpful links

General Publications

• Daubert MA, Yow E, Dunn G, Marchev S, Barnhart H, Douglas PS, O'Connor C, Goldstein S, Udelson JE, Sabbah HN. Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. Circ Heart Fail. 2017 Dec;10(12):e004389. doi: 10.1161/CIRCHEARTFAILURE.117.004389.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 1, 2015
• First Submitted That Met QC Criteria: March 9, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Estimate): September 17, 2015
• Last Update Submitted That Met QC Criteria: September 16, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Congestive Heart Failure; MTP-131; Bendavia™
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: SPIHF-101