Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: 4 mg elamipretide; 40 mg elamipretide; Placebo
Intervention description: Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days; Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days; Subcutaneous injection of placebo administered once daily for 28 consecutive days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 71.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This was a randomized, double-blinded, placebo-controlled, multiple-dose study in subjects
      with stable heart failure (HF) with reduced ejection fraction (HFrEF).
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  Anemia, defined as hemoglobin < 9 g/dL or planned blood transfusions in the next 6
             weeks.

          -  Estimated glomerular filtration rate (eGFR) < 30 mL/min, using the Modification of
             Diet in Renal Disease (MDRD) Study equation.

          -  History of hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection,
             or diagnosis of immunodeficiency.

          -  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.

          -  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.

          -  Female subjects who are pregnant, planning to become pregnant, or lactating.

          -  Requiring any change in doses of cardiovascular medication (including diuretics) in
             order to control worsening of HF symptoms.

          -  Known allergy to gadolinium.

          -  Currently receiving treatment with therapeutic doses of anticoagulants. Antiplatelet
             therapy used to prevent cardiovascular disease (primary prevention) or to treat
             chronic disease (secondary prevention) is permitted.

          -  Currently receiving treatment with sacubitril/valsartan or trimetazidine.

          -  Hyponatremia defined as plasma Na+ level <125 mEq/L (UK only).