Phase 2
N=71
Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction
Heart Failure
Bottom Line
View on ClinicalTrials.gov: NCT02788747 ↗Enrolled (actual)
71
Serious AEs
1.4%
Results posted
Apr 2020
Primary outcome: Primary: Change in Left Ventricular End Systolic Volume (ml) — -4.4; -1.2; -3.8 mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- 4 mg elamipretide (Drug); 40 mg elamipretide (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Stealth BioTherapeutics Inc.
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Left Ventricular End Systolic Volume (ml) |
-4.4; -1.2; -3.8 | — |
| SECONDARY Change in Left Ventricular Ejection Fraction (% of Blood Volume) |
2.2; 1.5; 2.3 | — |
| SECONDARY Change in Left Ventricular End Diastolic Volume (ml) as Measured by MRI |
-2.8; 0.5; -2.2 | — |
| SECONDARY Change in Left Ventricular Stroke Volume (ml) |
3.1; 3.7; 3.0 | — |
| SECONDARY Change in Left Ventricular Cardiac Output (L/Min) |
0.21; -0.01; 0.27 | — |
| SECONDARY Change in Left Ventricular Myocardial Mass (g) |
0.0; -0.4; -0.0 | — |
| SECONDARY Change in Right Ventricular End Systolic Volume (mL) |
-0.9; -0.8; -0.6 | — |
| SECONDARY Change in Right Ventricular End Diastolic Volume (mL) |
0.5; -1.2; -0.0 | — |
| SECONDARY Change in Right Ventricular Ejection Fraction (% Blood Volume) |
1.4; 0.4; 1.2 | — |
| SECONDARY Change in Early and Late Mitral Inflow Velocity Ratio |
-0.04; -0.03; -0.07 | — |
| SECONDARY Change in Early Mitral Inflow Velocity and Mitral Annular Early Diastolic Velocity Ratio (E/e') |
-0.94; 0.47; -0.20 | — |
| SECONDARY Change in Left Atrial Volume (mL) |
-3.4; -0.2; 1.6 | — |
| SECONDARY Change in Left Ventricular Global Longitudinal Strain Assessment (%) |
-1.76; -1.50; -1.46 | — |
| SECONDARY Change in Left Ventricular End Diastolic Volume (mL) as Measured by Echocardiography |
-1.1; 1.6; 2.0 | — |
| SECONDARY Change in Left Ventricular End Systolic Volume (mL) as Measured by Echocardiography |
-1.9; -0.5; 0.6 | — |
| SECONDARY Change in Biplane Ejection Fraction (mL) |
1.8; 2.0; 1.5 | — |
| SECONDARY Left Ventricular Mass Assessment (g) |
3.0; -4.2; -0.7 | — |
| SECONDARY Change in Tricuspid Regurgitation Severity Assessment (cm²) |
-1.03; 0.25; -0.30 | — |
| SECONDARY Change in Right Ventricular Fractional Area (%) |
0.1; 0.1; 0.9 | — |
| SECONDARY Change in Right Ventricular Systolic Pressure (mmHg) |
5.7; -1.5; -7.0 | — |
| SECONDARY Change in Mitral Regurgitation Severity (cm²) |
0.70; -0.71; -0.73 | — |
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.
- Hi
Data sourced from ClinicalTrials.gov (NCT02788747). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.