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

NCT02788747 | Completed Phase 2 Results

• 2 other identifiers: SPIHF-2012014-005724-10
• Study Type: interventional
• Target: 71
• Locations: 3 countries
• Sites: 15

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).

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Change in Left Ventricular End Systolic Volume (ml)

  Change in left ventricular end systolic volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  Baseline to Week 4

Secondary Outcomes (20)

• Change in Left Ventricular Ejection Fraction (% of Blood Volume)

  Baseline to Week 4

• Change in Left Ventricular End Diastolic Volume (ml) as Measured by MRI

  Baseline to Week 4

• Change in Left Ventricular Stroke Volume (ml)

  Baseline to Week 4

• Change in Left Ventricular Cardiac Output (L/Min)

  Baseline to Week 4

• Change in Left Ventricular Myocardial Mass (g)

  Baseline to Week 4

Study Arms (3)

4 mg elamipretide

EXPERIMENTAL

4 mg elamipretide once daily for 28 consecutive days

Drug: 4 mg elamipretide

40 mg elamipretide

EXPERIMENTAL

40 mg elamipretide once daily for 28 consecutive days

Drug: 40 mg elamipretide

Placebo

PLACEBO COMPARATOR

Placebo once daily for 28 consecutive days

Drug: Placebo

Interventions

4 mg elamipretide DRUG

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

Also known as: MTP-131, Bendavia

4 mg elamipretide

40 mg elamipretide DRUG

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

Also known as: MTP-131, Bendavia

40 mg elamipretide

Placebo DRUG

Subcutaneous injection of placebo administered once daily for 28 consecutive days

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead

Study Sites (15)

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

Bergamo, 24127, Italy

Location

A.O. Spedali Civili di Brescia Cardiologia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Brotzu Cardiologia

Cagliari, 09134, Italy

Location

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

Milan, 20138, Italy

Location

Ospedale Niguarda Ca' Granda SC Cardiologia 2

Milan, 20162, Italy

Location

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

Monza, 20900, Italy

Location

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

Pavia, 27100, Italy

Location

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

Pisa, 56124, Italy

Location

Deventer Hospital, Department of Cardiology

Deventer, 7416 SE, Netherlands

Location

University Medical Centre Groningen

Groningen, 9713 GZ, Netherlands

Location

Anthonius Ziekenhuis, Cardiology Department

Sneek, 8601 ZK, Netherlands

Location

Elisabeth Twee Steden Hospital (ETZ), Department of Cardiology

Tilburg, 5022 GC, Netherlands

Location

Gelre Ziekenhuis Zutphen, Department of Cardiology

Zutphen, 7207 AE, Netherlands

Location

Ninewells Hospital and Medical School

Dundee, DDI 9SY, United Kingdom

Location

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

London, EC1M 6BQ, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Jim Carr PharmD Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics Inc.

jim.carr@stealthbt.com

617-600-6888

Study Officials

• Gerasimos Filippatos, MD

  University of Athens, School of Medicine, Athens, Greece

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2016
• First Posted: June 2, 2016
• Study Start: June 1, 2016
• Primary Completion: September 1, 2017
• Study Completion: October 1, 2017
• Last Updated: May 14, 2020
• Results First Posted: April 22, 2020

Record last verified: 2020-04

Locations

IT (8); NL (5); GB (2)