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Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction

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ClinicalTrials.gov Identifier: NCT02788747
Recruitment Status : Completed
First Posted : June 2, 2016
Results First Posted : April 22, 2020
Last Update Posted : May 14, 2020
Sponsor:
Information provided by (Responsible Party):
Stealth BioTherapeutics Inc.

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

Condition or disease Intervention/treatment Phase
Heart Failure Drug: 4 mg elamipretide Drug: 40 mg elamipretide Drug: Placebo Phase 2

Detailed Description:

This was a randomized, double-blinded, placebo-controlled, multiple-dose study in subjects with stable heart failure (HF) with reduced ejection fraction (HFrEF). After completing the Screening period, a total of 71 subjects were randomized, in a 1:1:1 ratio, to receive either placebo, 4 mg elamipretide, or 40 mg elamipretide once daily for 28 consecutive days.

Each treatment group went through 3 distinct periods: Screening, Treatment, and Follow up.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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 Fraction
Actual Study Start Date : June 2016
Actual Primary Completion Date : September 2017
Actual Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: 4 mg elamipretide
4 mg elamipretide once daily for 28 consecutive days
Drug: 4 mg elamipretide
Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
Other Names:
  • MTP-131
  • Bendavia

Experimental: 40 mg elamipretide
40 mg elamipretide once daily for 28 consecutive days
Drug: 40 mg elamipretide
Subcutaneous injection of 40 mg elamipretide administered 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




Primary Outcome Measures :
  1. Change in Left Ventricular End Systolic Volume (ml) [ Time Frame: Baseline to Week 4 ]
    Change in left ventricular end systolic volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.


Secondary Outcome Measures :
  1. Change in Left Ventricular Ejection Fraction (% of Blood Volume) [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular Ejection Fraction as measured by percentage of blood volume from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  2. Change in Left Ventricular End Diastolic Volume (ml) as Measured by MRI [ Time Frame: Baseline to Week 4 ]
    Change from baseline in Left Ventricular End Diastolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  3. Change in Left Ventricular Stroke Volume (ml) [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular Stroke Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  4. Change in Left Ventricular Cardiac Output (L/Min) [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular Cardiac Output as measured by L/min from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  5. Change in Left Ventricular Myocardial Mass (g) [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular Myocardial Mass as measured by grams from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  6. Change in Right Ventricular End Systolic Volume (mL) [ Time Frame: Baseline to Week 4 ]
    Change in Right Ventricular End Systolic Volume as measured by mL from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  7. Change in Right Ventricular End Diastolic Volume (mL) [ Time Frame: Baseline to Week 4 ]
    Change in Right Ventricular End Diastolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  8. Change in Right Ventricular Ejection Fraction (% Blood Volume) [ Time Frame: Baseline to Week 4 ]
    Change in Right Ventricular Ejection Fraction as measured by percentage of blood volume from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

  9. Change in Early and Late Mitral Inflow Velocity Ratio [ Time Frame: Baseline to Week 4 ]
    Change in Early and Late Mitral Inflow Velocity Ratio from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  10. Change in Early Mitral Inflow Velocity and Mitral Annular Early Diastolic Velocity Ratio (E/e') [ Time Frame: Baseline to Week 4 ]
    Change in Early Mitral Inflow Velocity and Mitral Annular Early Diastolic Velocity Ratio as measured by E/e' from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  11. Change in Left Atrial Volume (mL) [ Time Frame: Baseline to Week 4 ]
    Change in Left Atrial Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  12. Change in Left Ventricular Global Longitudinal Strain Assessment (%) [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular Global Longitudinal Strain Assessment as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  13. Change in Left Ventricular End Diastolic Volume (mL) as Measured by Echocardiography [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular End Diastolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  14. Change in Left Ventricular End Systolic Volume (mL) as Measured by Echocardiography [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular End Systolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  15. Change in Biplane Ejection Fraction (mL) [ Time Frame: Baseline to Week 4 ]
    Change in Biplane Ejection Fraction as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  16. Left Ventricular Mass Assessment (g) [ Time Frame: Baseline to Week 4 ]
    Change in Left Ventricular Mass Assessment as measured by grams from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  17. Change in Tricuspid Regurgitation Severity Assessment (cm²) [ Time Frame: Baseline to Week 4 ]
    Change in Tricuspid Regurgitation Severity Assessment as measured by cm from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  18. Change in Right Ventricular Fractional Area (%) [ Time Frame: Baseline to Week 4 ]
    Change Right Ventricular Fractional Area in as measured by percentage from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  19. Change in Right Ventricular Systolic Pressure (mmHg) [ Time Frame: Baseline to Week 4 ]
    Change in Change in Right Ventricular Systolic Pressure as measured by mmHg from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

  20. Change in Mitral Regurgitation Severity (cm²) [ Time Frame: Baseline to Week 4 ]
    Change in Mitral Regurgitation Severity as measured by cm² from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02788747


Locations
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Italy
A.O. Papa Giovanni XXIII Cardiologia 1, Torre 5
Bergamo, Italy, 24127
A.O. Spedali Civili di Brescia Cardiologia
Brescia, Italy, 25123
Azienda Ospedaliera Brotzu Cardiologia
Cagliari, Italy, 09134
Centro Cardiologico Monzino U.O. Scompenso, Cardiologia Clinica e Cardiologia Riabilitativa
Milano, Italy, 20138
Ospedale Niguarda Ca' Granda SC Cardiologia 2
Milano, Italy, 20162
Cardiologia clinica, Unità dello Scompenso e Terapia intensive Reparto Carlo Magno, Faggi Policlinico di Monza
Monza, Italy, 20900
Dip. Cardiotoracovascolare: Cardiologia Fondazione IRCCS Policlinico San Matteo Pad. Nuovo Ospedale "DEA" Degenza: PIANO +3 Ambulatori: P.T. e P+3
Pavia, Italy, 27100
Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanità Pubblica
Pisa, Italy, 56124
Netherlands
Deventer Hospital, Department of Cardiology
Deventer, Netherlands, 7416 SE
University Medical Centre Groningen
Groningen, Netherlands, 9713 GZ
Anthonius Ziekenhuis, Cardiology Department
Sneek, Netherlands, 8601 ZK
Elisabeth Twee Steden Hospital (ETZ), Department of Cardiology
Tilburg, Netherlands, 5022 GC
Gelre Ziekenhuis Zutphen, Department of Cardiology
Zutphen, Netherlands, 7207 AE
United Kingdom
Ninewells Hospital and Medical School
Dundee, United Kingdom, DDI 9SY
William Harvey Heart Centre CRC, (Barts Health NHS Trust)
London, United Kingdom, EC1M 6BQ
Sponsors and Collaborators
Stealth BioTherapeutics Inc.
Investigators
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Study Chair: Gerasimos Filippatos, MD University of Athens, School of Medicine, Athens, Greece
  Study Documents (Full-Text)

Documents provided by Stealth BioTherapeutics Inc.:
Study Protocol  [PDF] March 21, 2017
Statistical Analysis Plan  [PDF] December 4, 2017

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Responsible Party: Stealth BioTherapeutics Inc.
ClinicalTrials.gov Identifier: NCT02788747    
Other Study ID Numbers: SPIHF-201
2014-005724-10 ( EudraCT Number )
First Posted: June 2, 2016    Key Record Dates
Results First Posted: April 22, 2020
Last Update Posted: May 14, 2020
Last Verified: April 2020
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases