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

NCT ID: NCT02388464

Last Updated: 2015-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-06-30

Brief Summary

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).

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Low dose

Group Type: EXPERIMENTAL

MTP-131

Intervention Type: DRUG

MTP-131 (low dose) administered as single intravenous infusion over 4 hours

Intermediate dose

Group Type: EXPERIMENTAL

MTP-131

Intervention Type: DRUG

MTP-131 (intermediate dose) administered as single intravenous infusion over 4 hours

High dose

Group Type: EXPERIMENTAL

MTP-131

Intervention Type: DRUG

MTP-131 (high dose) administered as single intravenous infusion over 4 hours

Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo Comparator (at each dose cohort) administered as single intravenous infusion over 4 hours

Interventions

MTP-131

MTP-131 (low dose) administered as single intravenous infusion over 4 hours

Intervention Type: DRUG

MTP-131

MTP-131 (intermediate dose) administered as single intravenous infusion over 4 hours

Intervention Type: DRUG

MTP-131

MTP-131 (high dose) administered as single intravenous infusion over 4 hours

Intervention Type: DRUG

Placebo

Placebo Comparator (at each dose cohort) administered as single intravenous infusion over 4 hours

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jim Carr, PharmD

Role: STUDY_DIRECTOR

Stealth BioTherapeutics Inc.

Sotir Marchev, MD,PhD, FESC

Role: PRINCIPAL_INVESTIGATOR

Bulgaria

Locations

Sevlievo, Gabrovo, Bulgaria

Countries

Bulgaria

References

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.

Reference Type: DERIVED

PMID: 29217757 (View on PubMed)

Other Identifiers

SPIHF-101

Identifier Type: -

Identifier Source: org_study_id