Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction

NCT ID: NCT02788747

Last Updated: 2020-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2017-10-31

Brief Summary

This was a randomized, double-blinded, placebo-controlled, multiple-dose study in subjects with stable heart failure (HF) with reduced ejection fraction (HFrEF).

Detailed Description

This was a randomized, double-blinded, placebo-controlled, multiple-dose study in subjects with stable heart failure (HF) with reduced ejection fraction (HFrEF). After completing the Screening period, a total of 71 subjects were randomized, in a 1:1:1 ratio, to receive either placebo, 4 mg elamipretide, or 40 mg elamipretide once daily for 28 consecutive days.

Each treatment group went through 3 distinct periods: Screening, Treatment, and Follow up.

Conditions

Heart Failure

Study Design

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

Study Groups

4 mg elamipretide

4 mg elamipretide once daily for 28 consecutive days

Group Type: EXPERIMENTAL

4 mg elamipretide

Intervention Type: DRUG

Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days

40 mg elamipretide

40 mg elamipretide once daily for 28 consecutive days

Group Type: EXPERIMENTAL

40 mg elamipretide

Intervention Type: DRUG

Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days

Placebo

Placebo once daily for 28 consecutive days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subcutaneous injection of placebo administered once daily for 28 consecutive days

Interventions

4 mg elamipretide

Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days

Intervention Type: DRUG

40 mg elamipretide

Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days

Intervention Type: DRUG

Placebo

Subcutaneous injection of placebo administered once daily for 28 consecutive days

Intervention Type: DRUG

Other Intervention Names

MTP-131; Bendavia; MTP-131; Bendavia

Eligibility Criteria

Inclusion Criteria

• Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures.
• Age ≥40 and ≤80 years.
• A known history of chronic ischemic or non-ischemic cardiomyopathy of at least 6 months duration from the time of the initial diagnosis.
• Receiving heart failure (HF) treatment, including, but not limited to, angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), and an evidence-based beta blocker for the treatment of HF. Subjects who cannot tolerate ACEI or ARB due to reduced renal function or hypotension are eligible. Subjects may be receiving aldosterone antagonists, but this is not a requirement for the study.
• HF is considered to be stable in the judgment of the Investigator AND doses of HF treatment have been stable for at least 1 month prior to the Screening Visit.
• In normal sinus rhythm (electrocardiogram documented) at Screening and Day 1 and no history of atrial fibrillation in the past 12 months
• No hospitalization related to HF within 1 month prior to the Screening Visit.
• Left Ventricular Ejection Fraction (LVEF) ≤ 40% by 2-D echocardiography at Screening.
• At least 3 viable segments (hyperenhancement ≤ 25%) by a qualifying delayed gadolinium-enhanced cardiac MRI examination at Screening (confirmed by independent core lab).
• Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until two months after the last dose of study medication:

• Abstinence, maintenance of monogamous relationship with a male partner who has been surgically sterilized by vasectomy, or barrier method AND either hormonal contraception or an intrauterine device or system.

Exclusion Criteria

• History of any concurrent medical condition which, in the opinion of the Investigator, significantly increased the potential risks associated with administration of study medication or any other aspect of study participation.
• Any contraindication to MRI scanning.
• Left ventricular end diastolic dimension (LVEDD) indexed to Body Surface Area is > 45 mm/m2.
• Coronary or peripheral revascularization procedures, valvular procedures, OR any major surgical procedure within 3 months prior to the Screening Visit.
• Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 3 months prior to the Screening Visit.
• Obstructive or restrictive cardiomyopathy, infiltrative diseases of the myocardium (e.g., amyloid, sarcoid, etc.) myocarditis, or reductions in LV function thought to be secondary primarily to valvular heart disease, prior cardiac valve surgery or known aortic stenosis.
• The presence or anticipated placement of any pacemaker, implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) devices during the ensuing 6-week study period.
• Presence of second degree or advanced heart block.
• Uncontrolled hypertension defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 110 mmHg on at least two consecutive readings.
• Presence of any left ventricular thrombus, pericardial disease, uncorrected thyroid disease or a dyskinetic left ventricular aneurysm.
• History of cancer that causes symptoms, disabilities, or is likely to lead to hospitalization or treatment in the next 12 months.
• Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or has received prior radiation therapy to the chest.
• Liver enzymes (alanine aminotransferase [ALT] AND/OR aspartate. aminotransferase [AST]) elevation > 3 times the upper limit of normal (ULN).
• Total bilirubin > 1.5 times ULN in the absence of Gilbert's Syndrome.
• Bleeding diathesis or any known blood dyscrasia.
• Anemia, defined as hemoglobin < 9 g/dL or planned blood transfusions in the next 6 weeks.
• Estimated glomerular filtration rate (eGFR) < 30 mL/min, using the Modification of Diet in Renal Disease (MDRD) Study equation.
• History of hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, or diagnosis of immunodeficiency.
• Known active drug or alcohol abuse within 1 year of the Screening Visit. Alcohol abuse is defined as 15 or more drinks for men per week or 8 or more for women.
• Recipient of any investigational drugs, stem cell or gene therapies, or devices OR participation in another clinical trial, within 3 months prior to the Screening Visit.
• Female subjects who are pregnant, planning to become pregnant, or lactating.
• Requiring any change in doses of cardiovascular medication (including diuretics) in order to control worsening of HF symptoms.
• Known allergy to gadolinium.
• Currently receiving treatment with therapeutic doses of anticoagulants. Antiplatelet therapy used to prevent cardiovascular disease (primary prevention) or to treat chronic disease (secondary prevention) is permitted.
• Currently receiving treatment with sacubitril/valsartan or trimetazidine.
• Hyponatremia defined as plasma Na+ level <125 mEq/L (UK only).

• Minimum Eligible Age: 40 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

Gerasimos Filippatos, MD

Role: STUDY_CHAIR

University of Athens, School of Medicine, Athens, Greece

Locations

A.O. Papa Giovanni XXIII Cardiologia 1, Torre 5

Bergamo, , Italy

A.O. Spedali Civili di Brescia Cardiologia

Brescia, , Italy

Azienda Ospedaliera Brotzu Cardiologia

Cagliari, , Italy

Centro Cardiologico Monzino U.O. Scompenso, Cardiologia Clinica e Cardiologia Riabilitativa

Milan, , Italy

Ospedale Niguarda Ca' Granda SC Cardiologia 2

Milan, , Italy

Cardiologia clinica, Unità dello Scompenso e Terapia intensive Reparto Carlo Magno, Faggi Policlinico di Monza

Monza, , Italy

Dip. Cardiotoracovascolare: Cardiologia Fondazione IRCCS Policlinico San Matteo Pad. Nuovo Ospedale "DEA" Degenza: PIANO +3 Ambulatori: P.T. e P+3

Pavia, , Italy

Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica

Pisa, , Italy

Deventer Hospital, Department of Cardiology

Deventer, , Netherlands

University Medical Centre Groningen

Groningen, , Netherlands

Anthonius Ziekenhuis, Cardiology Department

Sneek, , Netherlands

Elisabeth Twee Steden Hospital (ETZ), Department of Cardiology

Tilburg, , Netherlands

Gelre Ziekenhuis Zutphen, Department of Cardiology

Zutphen, , Netherlands

Ninewells Hospital and Medical School

Dundee, , United Kingdom

William Harvey Heart Centre CRC, (Barts Health NHS Trust)

London, , United Kingdom

Countries

Italy; Netherlands; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-005724-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPIHF-201

Identifier Type: -

Identifier Source: org_study_id