A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effects of Multiple Subcutaneous Injections of Elamipretide on Left Ventricular Function in Subjects with Stable Heart Failure with Reduced Ejection Fractio

Phase 1

Conditions: Stable Heart Failure with Reduced Ejection Fraction
MedDRA version: 19.1Level: LLTClassification code 10008908Term: Chronic heart failureSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2014-005724-10-NL

Lead Sponsor: Stealth BioTherapeutics Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 70

Inclusion Criteria

1. Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures.
2. Age =40 and =80 years.
3. A known history of chronic ischemic or non-ischemic cardiomyopathy of at least 6 months duration from the time of the initial diagnosis, or signs and symptoms consistent with heart failure.
4. 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.
5. 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.
6. In normal sinus rhythm (electrocardiogram documented) at Screening and Day 1 and no history of atrial fibrillation in the past 12 months
7. No hospitalization related to HF within 1 month prior to the Screening Visit.
8. Left Ventricular Ejection Fraction (LVEF) = 40% by 2-D echocardiography at Screening.
9. At least 3 viable segments (hyperenhancement = 25%) by a qualifying delayed gadolinium-enhanced cardiac MRI examination at Screening (confirmed by independent core lab).
10. Willing to adhere to the study requirements for the length of the trial.
11. 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, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use an acceptable method of contraception should they become sexually active.
b. Maintenance of monogamous relationship with a male partner who has been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit or confirmed via sperm analysis).
c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system.

Note: Non-childbearing potential is defined as surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or tubal ligation) or postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to the Screening Visit).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1. History of any concurrent medical condition which, in the opinion of the Investigator, significantly increases the potential risks associated with administration of study medication or any other aspect of study participation.
2. Any contraindication to MRI scanning as assessed by local MRI safety questionnaire, which may include:
a. History of intra-orbital metal fragments which have not been removed
b. Severe claustrophobia
c. Non-MRI safe cochlear implant(s) or intracranial aneurysm clips
d. Extensive tattoos located on the torso that contain metallic inks
e. Other non-removable implanted metallic or electronic devices that have not been determined to be MRI safe
f. Inability to lie flat
3. Inadequate echocardiogram image quality (defined as poor sound transmission and/or < 10 endocardial segments seen).
4. LVEDD indexed to Body Surface Area is > 45 mm/m2 assessed by 2-D echocardiography.
5. Coronary or peripheral revascularization procedures, valvular procedures, OR any major surgical procedure within 3 months prior to the Screening Visit.
6. Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 3 months prior to the Screening Visit.
7. 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.
8. 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.
9. Presence of second degree or advanced heart block.
10. Uncontrolled hypertension defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 110 mmHg on at least two consecutive readings.
11. Presence of any left ventricular thrombus, pericardial disease, uncorrected thyroid disease or a dyskinetic left ventricular aneurysm.
12. History of cancer that causes symptoms, disabilities, or is likely to lead to hospitalization or treatment in the next 12 months.
13. Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or has received prior radiation therapy to the chest.
14. Liver enzymes (alanine aminotransferase [ALT] AND/OR aspartate aminotransferase[AST]) elevation > 3 times the upper limit of normal (ULN).
15. Total bilirubin > 1.5 times ULN in the absence of Gilbert’s Syndrome.
16. Bleeding diathesis or any known blood dyscrasia.
17. Anemia, defined as hemoglobin < 9 g/dL or planned blood transfusions in the next 6 weeks.
18. Estimated glomerular filtration rate (eGFR) < 30 mL/min, using the Modification of Diet in Renal Disease (MDRD) Study equation:
eGFR (mL/min/1.73 m2) = 175 x (Scr)^[-1.154] x (Age)^[-0.203] x (0.742 if female) x (1.212 if African American)
19. History of hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, or diagnosis of immunodeficiency.
20. 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.
21. 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.
22. Any significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromi

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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