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

Chronic Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02814097
• Other study ID #: SPIHF-203
• Secondary ID: 2015-005615-32
• Status: Completed
• Phase: Phase 2
• First received: June 8, 2016
• Last updated: September 6, 2017
• Start date: September 2, 2016
• Est. completion date: June 2, 2017

Study information

• Verified date: September 2017
• Source: Stealth BioTherapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: June 2, 2017
• Est. primary completion date: May 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• elamipretide
Subcutaneous injection of 40 mg elamipretide once daily for 28 consecutive days
• Placebo
Subcutaneous injection of placebo administered once daily for 28 consecutive days

Locations

Country	Name	City	State
Germany	Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum	Berlin
Germany	German Heart Center	Berlin
Serbia	Clinical Centre of Serbia, Clinic for Cardiology	Belgrade
Serbia	Clinical Hospital Center "Bežanijska Kosa", Department of Cardiology	Belgrade
Serbia	Clinical Hospital Center "Dr Dragiša Mišovic-Dedinje", Department of Cardiology	Belgrade
Serbia	Clinical Hospital Center "Zemun", Department of Cardiology	Belgrade
Serbia	Clinical Hospital Center "Zvezdara", Department of Cardiology	Belgrade
Serbia	Clinical Center Niš, Clinic for Cardiology	Niš
Serbia	Institute for Cardiovascular Diseases Vojvodina, Clinic for Cardiology	Sremska Kamenica

Sponsors (3)

Lead Sponsor	Collaborator
Stealth BioTherapeutics Inc.	Charite University, Berlin, Germany, SCIRENT Clinical Research and Science d.o.o.

Countries where clinical trial is conducted

Germany,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the delta in E/e' at rest exercise measured with echocardiography between the elamipretide and placebo groups		4 weeks
Secondary	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
Secondary	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
Secondary	Compare the change in NT-proBNP, between the elamipretide and placebo groups at the end of the 4-week treatment period		4 weeks
Secondary	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