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

Sponsor

Stealth BioTherapeutics Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02814097

Collaborator

Charite University, Berlin, Germany (Other), SCIRENT Clinical Research and Science d.o.o. (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

5.1

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Heart Failure	Drug: elamipretide Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 2, 2016

Actual Primary Completion Date :

May 4, 2017

Actual Study Completion Date :

Jun 2, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Compare the delta in E/e' at rest exercise measured with echocardiography between the elamipretide and placebo groups [4 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum	Berlin	Germany	13353
2	German Heart Center	Berlin	Germany	13353
3	Clinical Centre of Serbia, Clinic for Cardiology	Belgrade	Serbia	11000
4	Clinical Hospital Center "Dr Dragiša Mišović-Dedinje", Department of Cardiology	Belgrade	Serbia	11000
5	Clinical Hospital Center "Zvezdara", Department of Cardiology	Belgrade	Serbia	11000
6	Clinical Hospital Center "Bežanijska Kosa", Department of Cardiology	Belgrade	Serbia	11080
7	Clinical Hospital Center "Zemun", Department of Cardiology	Belgrade	Serbia	11080
8	Clinical Center Niš, Clinic for Cardiology	Niš	Serbia	18000
9	Institute for Cardiovascular Diseases Vojvodina, Clinic for Cardiology	Sremska Kamenica	Serbia	21204