A Study to Evaluate the Effects of 4 Weeks Treatment With Subcutaneous Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Preserved Ejection Fraction

A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effects of 4 Weeks Treatment With Subcutaneous Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Preserved Ejection Fraction

This is a multi-center, randomized, double-blind, placebo-controlled study in subjects with stable heart failure with preserved ejection fraction (HFpEF) to evaluate the effects of 4 weeks treatment with subcutaneous MTP-131 (elampretide) on left ventricular function.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: elamipretide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • German Heart Center
  • Berlin, Germany, 13353
    • Charite Universitätsmedizin Berlin, Campus Virchow-Klinikum
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical centre of Serbia, Clinic for cardiology
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center "Dr Dragiša Mišović-Dedinje", Department of Cardiology
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center "Zvezdara", Department of Cardiology
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center "Bežanijska Kosa", Department of Cardiology
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center "Zemun", Department of Cardiology
  • Niš, Serbia, 18000
    • Clinical Center Niš, Clinic for Cardiology
  • Sremska Kamenica, Serbia, 21204
    • Institute for Cardiovascular Diseases Vojvodina, Clinic for Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥45 and <80 years.
• Symptomatic heart failure (i.e. NYHA II or III) due to HFpEF for at least 6 months prior to study start
• Evidence of HFpEF: LVEF ≥45% and E/e´>10 and NT-pro-BNP >220 pg/ml (sinus rhythm) / > 600 pg/mL (atrial fibrillation)
• An exercise-induced increase in E/e' of at least 1.5 units during stress echocardiography assessment.
• Heart failure is considered to be stable, in the judgment of the investigator, and no hospitalization for HFpEF or changes in dose regimen of pharmacologic treatment for HF has occurred within 1 month prior to the Screening Visit.
• Treatment with appropriate pharmacologic therapy to manage underlying risk factors according to current guidelines.

• 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:

  a) Abstinence, b) surgically sterilized male partner, or c) barrier method And hormonal contraception

• Women of child-bearing potential must have a negative serum pregnancy test at baseline
• Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures

Exclusion Criteria:

• Probable alternative diagnoses that in the opinion of the investigator could account for the patient's symptoms e.g. severe pulmonary dysfunction or severe asthma
• LVEF <45% (at the moment of enrollment or in medical history)
• Coronary or peripheral revascularization procedures, valvular procedures, OR any major surgical procedure within 3 months prior to the Screening Visit.
• Acute coronary syndrome (ACS), stroke or transient ischemic attack (TIA) within 3 months prior to the Screening Visit.
• Uncontrolled hypertension defined as a systolic blood pressure (BP) >160 mm Hg or a diastolic BP >100 mm Hg on at least 2 consecutive readings that will require a change in anti-hypertensive treatment during the study period.
• Active cancer or undergoing chemotherapy within previous 6 months
• Total bilirubin >2x the upper limit of normal (ULN) in the absence of Gilbert's Syndrome (M. Meulengracht) and liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] and/or alkaline phosphatase) elevation >3xULN
• Estimated glomerular filtration rate <30 mL/min, by MDRD
• Known active drug or alcohol abuse within 1 year of the Screening Visit.
• Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment
• Treatment with spironolactone or eplerenone for less than 3 months at study start
• Treatment with dabigatran
• Treatment with valsartan/sacubitril
• Female subjects who are pregnant, planning to become pregnant, or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40 mg elamipretide; 40 mg elamipretide once daily for 28 consecutive days	Drug: elamipretide; Subcutaneous injection of 40 mg elamipretide once daily for 28 consecutive days; Other Names: MTP-131; Bendavia
Placebo Comparator: Placebo; Placebo once daily for 28 consecutive days	Drug: Placebo; Subcutaneous injection of placebo administered once daily for 28 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Compare the delta in E/e' at rest exercise measured with echocardiography between the elamipretide and placebo groups	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Compare the change at rest and during submaximal stress in LV systolic global longitudinal strain (GLS) between the elamipretide and placebo groups at the end of the 4-week treatment period	4 weeks
Compare the change in 6-minute walking distance, between the elamipretide and placebo groups at the end of the 4-week treatment period	4 weeks
Compare the change in NT-proBNP, between the elamipretide and placebo groups at the end of the 4-week treatment period	4 weeks
Compare the percent of patients on elamipretide versus placebo presenting with TEAEs and SAEs, including changes in biomarkers of myocardial damage and changes in markers of renal function	4 weeks

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.
• Collaborators: Charite University, Berlin, Germany; SCIRENT Clinical Research and Science d.o.o.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2016
• Primary Completion (Actual): May 4, 2017
• Study Completion (Actual): June 2, 2017

Study Registration Dates

• First Submitted: June 8, 2016
• First Submitted That Met QC Criteria: June 22, 2016
• First Posted (Estimate): June 27, 2016

Study Record Updates

• Last Update Posted (Actual): September 7, 2017
• Last Update Submitted That Met QC Criteria: September 6, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Heart Failure; MTP-131; HFpEF; elamipretide; Bendavia™
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: SPIHF-203; 2015-005615-32 (EudraCT Number)