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

Phase 1
Completed
Conditions
Congestive Heart Failure
Interventions
Drug: Placebo
Registration Number
NCT02388464
Lead Sponsor
Stealth BioTherapeutics Inc.
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intermediate doseMTP-131-
High doseMTP-131-
PlaceboPlacebo-
Low doseMTP-131-
Primary Outcome Measures
NameTimeMethod
Incidence of Adverse EventsAssessed up to Day 7
Secondary Outcome Measures
NameTimeMethod
Left ventricular ejection fraction assessed by 2-D echocardiographyAssessed up to 24 hours post-infusion start
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