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

Congestive Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02388464
• Other study ID #: SPIHF-101
• Status: Completed
• Phase: Phase 1
• First received: March 1, 2015
• Last updated: September 16, 2015
• Start date: July 2014
• Est. completion date: June 2015

Study information

• Verified date: September 2015
• Source: Stealth BioTherapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• MTP-131
MTP-131 (low dose) administered as single intravenous infusion over 4 hours
• MTP-131
MTP-131 (intermediate dose) administered as single intravenous infusion over 4 hours
• MTP-131
MTP-131 (high dose) administered as single intravenous infusion over 4 hours
• Placebo
Placebo Comparator (at each dose cohort) administered as single intravenous infusion over 4 hours

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Stealth BioTherapeutics Inc.

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events		Assessed up to Day 7	Yes
Secondary	Left ventricular ejection fraction assessed by 2-D echocardiography		Assessed up to 24 hours post-infusion start	No