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

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

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.

Study Overview

• Status: Withdrawn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

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Gabrovo
    • Sevlievo, Gabrovo, Bulgaria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (ANTICIPATED): September 1, 2015
• Study Completion (ANTICIPATED): October 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): October 15, 2015
• Last Update Submitted That Met QC Criteria: October 14, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Heart Failure; MTP-131; Bendavia™
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: SPIHF-202