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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: elamipretide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 mg elamipretide<br>20 mg elamipretide once daily for 7 consecutive days | Drug: elamipretide<br>* 20 mg elamipretide administered intravenously once daily for 7 consecutive days<br>* Other names: MTP-131, Bendavia;|
| Placebo Comparator: Placebo<br>Placebo once daily for 7 consecutive days | Drug: Placebo<br>* Placebo administered intravenously once daily for 7 consecutive days<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |  | 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 |  | 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 |  | 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. |  | 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 |  | 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. |  | Baseline to Day 8 | 
| Half-life (T1/2) |  | Baseline to Day 8 | 
| Area under the concentration - time curve from 0-24 h (AUC 0-24) |  | Baseline to Day 8 | 
| Area under the concentration - time curve from 0- infinity (AUC 0-∞) |  | Baseline to Day 8 | 
| Peak Plasma Concentration (Cmax) |  | Baseline to Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, diuresis, dropsy, congestion, elamipretide, MTP-131, Bendavia™