A Phase 2 Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment With Elamipretide in Patients Hospitalized With Congestion Due to Heart Failure

July 26, 2020 updated by: Stealth BioTherapeutics Inc.

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment With Elamipretide in Patients Hospitalized With Congestion Due to Heart Failure

This is a phase 2 randomized, double-blind, placebo-controlled study to evaluate the cardiac and renal effects of short term treatment with elamipretide in patients hospitalized with congestion due to heart failure

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

308

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium, 9300
        • Hospital Onze Lieve Vrouw campus Aalst
      • Antwerp, Belgium, 2020
        • Hospital ZNA Middelheim
  • Bulgaria
      • Dimitrovgrad, Bulgaria, 6400
        • Department of Internal Diseases, "Multiprofile Hospital for Active Treatment Sveta Ekaterina - Dimitrovgrad" EOOD
      • Sofia, Bulgaria, 1202
        • Clinic of Cardiology, "Second Multiprofile Hospital for Active Treatement - Sofia" EAD
      • Sofia, Bulgaria, 1309
        • Clinic of Cardiology, Multiprofile Hospital for Active Treatment National Heart Hospital" EAD
      • Sofia, Bulgaria, 1407
        • Clinic of Cardiology, "City Clinic University Multiprofile Hospital for Active Treatment" EOOD
      • Sofia, Bulgaria, 1750
        • Clinic of Internal Diseases, "Multiprofile Hospital for Active Treatment, "Sveta Anna Sofia" AD
      • Veliko Tarnovo, Bulgaria, 5000
        • Department of Cardiology, "Multiprofile Regional Hospital for Active Treatement Dr. Stefan Cherkezov" AD
  • France
      • Créteil, France, 94000
        • Hopital Henri Mondor
      • Toulouse Cedex 9, France, 31059
        • CHU de Rangueil
  • Hungary
      • Budapest, Hungary, 1122
        • Semmelweis University Heart and Vascular Center
      • Budapest, Hungary, 1096
        • Hungarian Institute Of Cardiology, Department of Adult Cardiology
      • Székesfehérvár, Hungary, 8000
        • County St. George University Teaching Hospital, Department of Internal Medicine Cardiology
      • Zalaegerszeg, Hungary, 8900
        • Zala County Hospital Cardiology Department
  • Latvia
      • Daugavpils, Latvia, LV5417
        • Daugavpils Regional Hospital
      • Liepaja, Latvia, LV1038
        • Riga East Clinical University Hospital, Clinic Gailezers
      • Liepaja, Latvia, LV3402
        • Liepaja Regional Hospital
      • Riga, Latvia, LV1002
        • Pauls Stradins Clinical University Hospital, Latvian Centre of Cardiology
  • Netherlands
      • Deventer, Netherlands, 7416 S
        • Deventer Hospital
      • Ede, Netherlands, 6716 RP
        • Hospital Gelderse Vallei
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen
      • Hertogenbosch, Netherlands, 5223 GV 's
        • Hospital Jeroen Bosch
      • Sneek, Netherlands, 8601 ZR
        • Hospital Antonius/D&A research Genetic
      • Tilburg, Netherlands, 5042 AD
        • Hospital Elisabeth -Tweesteden
      • Zutphen, Netherlands, 7207 AE
        • Hospitals Gelre
  • Poland
      • Lodz, Poland, 91-347
        • Bieganski Provincial Specialist Hospital, Department of Cardiology, Clinic of Cardiology UM
      • Warsaw, Poland, 04-628
        • Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic Heart Failure and Transplantation
      • Warsaw, Poland, 04-628
        • Cardinal Stefan Wyszynski, Institute of Cardiology, Clinic of Coronary Heart Disease and Structural Heart Disease
  • Serbia
      • Belgrade, Serbia, 11080
        • Clinical Hospital Centre Zemun
      • Belgrade, Serbia, 11000
        • Clinical Centre of Serbia, Emergency Centre
      • Belgrade, Serbia, 11000
        • Clinical Centre of Serbia, Institute for Cardiovascular Diseases
      • Belgrade, Serbia, 11070
        • Clinical Hospital Centre Bezanijska Kosa
      • Nis, Serbia, 18000
        • Clinical Centre Nis
      • Sremska Kamenica, Serbia, 21204
        • Institute for Cardiovascular Diseases of Vojvodina
  • Spain
      • Barcelona, Spain, 08907
        • Hospital Universitario de Bellvitge
      • Coruña, Spain, 15006 A
        • Complexo Hospitalario Universitario de A Coruña
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Madrid, Spain, 28222 Majadahonda
        • Hospital Universitario Puerta de Hierro Majadahonda
      • Pontevedra, Spain, 36312 Vigo
        • Hospital Alvaro Cunqueiro
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46014
        • Consorci Hospital General Universitari de València
  • United Kingdom
      • Bradford, United Kingdom, BD6 6RJ
        • Bradford Royal Infirmary
      • Leicester, United Kingdom, LE3 9QP
        • Glenfield Hospital
      • Torquay, United Kingdom, TQ2 7AA
        • Torbay Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • A history of chronic heart failure for at least 1 month
  • Treated with ≥40 mg/day of furosemide or bumetanide ≥1 mg/day or torasemide ≥10 mg/day for at least 1 month
  • In-hospital observation/admission and treatment for ≤72 hours and primary cause for admission is heart failure with persistent congestion in the opinion of the Investigator (i.e. at least +2 pitting oedema and/or an estimated 8 kg gain in weight over baseline over the past 4 weeks) requiring intravenous loop diuretic therapy
  • Sufficiently severe oedema to justify treatment by an intravenous infusion of furosemide of 10 mg/hour for at least 48 hours
  • Systolic blood pressure >90 mmHg and considered to be haemodynamically stable, in the opinion of the Investigator
  • History of left ventricular ejection fraction (LVEF) ≤40% confirmed in the last 18 months
  • NT-proBNP >1500 pg/ml or BNP >500 pg/ml
  • An eGFR of >30 mL/min/1.73 m2 using the 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)

Exclusion Criteria:

  • Acute coronary syndrome, stroke, or transient ischemic attack (TIA), coronary or peripheral revascularization procedures, valve procedures, OR any major surgical procedure within the previous 6 weeks
  • Invasive cardiac investigation and/or treatment (i.e. coronary angiography, percutaneous coronary intervention [PCI] or surgery) or other surgical procedure planned in the next 4 weeks
  • Use of intravenous radiographic contrast agent within 72 hours prior to screening or planned use during the study
  • Severe, in the investigators opinion, uncorrected valve disease or congenital heart disease as the cause for cardiac decompensation
  • Acute mechanical cause of decompensated heart failure such as papillary muscle rupture
  • Obstructive or infiltrative cardiomyopathy (e.g. amyloid, sarcoid, etc), suspected acute myocarditis, or heart failure related to an untreated metabolic condition (e.g. haemochromatosis)
  • Second or third degree heart block unless the subject has a ventricular pacemaker
  • Atrial fibrillation/flutter with sustained ventricular response of >130 bpm
  • Placement of a ventricular resynchronization device within the previous 6 weeks
  • Treatment or planned treatment with intravenous inotropic agents other than digoxin at any time on this admission
  • Receipt of intravenous vasodilator therapy ≤ 6 hours prior to randomization
  • The presence of any mechanical assist device or listed for or a history of a heart transplant
  • Severe respiratory disease or anticipated need for mechanical respiratory support (i.e. mechanical ventilation)
  • Anuric in the previous 24 hours
  • Haemoglobin <9 g/dL at screening or planned blood transfusions in the next 30 days
  • Serum potassium >5.5 mEq/L
  • Marked proteinuria suggestive of nephrotic syndrome
  • Estimated GFR (eGFR) as per MDRD equation <30 ml/min
  • Serum albumin of < 2.8 g/dL
  • Liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) elevation >5 times the upper limit of normal (ULN)
  • Total bilirubin >2.0 times ULN in the absence of Gilbert's Syndrome
  • Current or planned ultrafiltration, paracentesis, haemofiltration or dialysis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 20 mg elamipretide
20 mg elamipretide once daily for 7 consecutive days
Drug: elamipretide
20 mg elamipretide administered intravenously once daily for 7 consecutive days
Other Names:
  • MTP-131, Bendavia
Placebo Comparator: Placebo
Placebo once daily for 7 consecutive days
Drug: Placebo
Placebo administered intravenously once daily for 7 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in NT-proBNP between Baseline and Day 8/Early Discharge
Time Frame: Baseline to Day 8
Baseline to Day 8

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of patients staying in the same functional renal function class measured with MDRD formula compared to the number of patients with decreasing or increasing renal function measured with MDRD formula
Time Frame: Baseline to Day 3 and Day 8
Baseline to Day 3 and Day 8
Number of patients showing a decrease in body weight compared to baseline as well as number of patients showing either no decrease or an increase in body weight compared to baseline
Time Frame: Baseline to Day 3 and Day 8
Baseline to Day 3 and Day 8
Calculation of decrease or increase in body weight normalised to the average dose (in mg) of furosemide administered
Time Frame: Baseline to Day 3 and Day 8
Baseline to Day 3 and Day 8
The patient and physician global assessment is a 7-point scale which either the patient or the physician will assess from 0 to 10 and will be mathematically averaged on a daily basis in order to compare the different averages throughout the study.
Time Frame: Baseline to Day 3 and Day 8
Baseline to Day 3 and Day 8
The average daily dose of diuretic (furosemide - adjusted for thiazide dose if administered) between baseline and Day 3 and Day 8/Early Discharge
Time Frame: Baseline to Day 3 and Day 8
Baseline to Day 3 and Day 8
All adverse events, serious adverse events and SUSARs will be summarised per treatment group, namely elamipretide versus placebo, and compared at the end of the study.
Time Frame: Baseline to Day 8
Baseline to Day 8
Half-life (T1/2)
Time Frame: Baseline to Day 8
Baseline to Day 8
Area under the concentration - time curve from 0-24 h (AUC 0-24)
Time Frame: Baseline to Day 8
Baseline to Day 8
Area under the concentration - time curve from 0- infinity (AUC 0-∞)
Time Frame: Baseline to Day 8
Baseline to Day 8
Peak Plasma Concentration (Cmax)
Time Frame: Baseline to Day 8
Baseline to Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stealth BioTherapeutics Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2016

Primary Completion (Actual)

November 27, 2017

Study Completion (Actual)

November 27, 2017

Study Registration Dates

First Submitted

September 14, 2016

First Submitted That Met QC Criteria

September 22, 2016

First Posted (Estimate)

September 26, 2016

Study Record Updates

Last Update Posted (Actual)

July 28, 2020

Last Update Submitted That Met QC Criteria

July 26, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPIHF-204
  • 2016-000126-19 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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