Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure (ATOMIC-AHF)

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared with placebo on dyspnea in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure. This is a multicenter, randomized, double-blind, placebo-controlled study with 3 dose cohorts enrolled sequentially in order of ascending dose strength of omecamtiv mecarbil. In each cohort, subjects are randomized 1:1 to omecamtiv mecarbil or placebo.

Detailed Description
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This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of IV Infusion Treatment With Omecamtiv Mecarbil in Subjects With Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: Omecamtiv mecarbil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 - 85 years Hospitalized for worsening heart failure, within 24 hours of initiating IV loop diuretic Dyspnea due to heart failure, at rest or with minimal exertion History of left ventricular ejection fraction (LVEF) ≤ 40% Elevated brain natriuretic peptide (BNP) or N-terminal fragment BNP (NT-proBNP) Exclusion Criteria: Receiving IV vasopressor (excluding low dopamine), inotropic or mechanical support Acute coronary syndrome (ACS) Within 30 days prior to enrollment: cardiac resynchronization therapy (CRT) or implantable cardioverter defibrillator (ICD) implantation, ACS, coronary revascularization, transient ischemic attack (TIA) or stroke, sustained ventricular arrhythmia, or major surgery Severe valvular stenosis, hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease Estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Omecamtiv mecarbil<br> | Drug: Omecamtiv mecarbil<br>* 48-hour infusion of omecamtiv mecarbil; dose strength will depend on cohort assignment.<br>* Other names: AMG 423;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 48-hour infusion of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of the study is to evaluate the effect of 48 hours of intravenous (IV) omecamtiv mecarbil compared with placebo on dyspnea in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure. |  | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize pharmacokinetics of omecamtiv mecarbil including metabolites following IV infusion and to evaluate the relationship between omecamtiv mecarbil plasma concentration and echocardiographic parameters in subjects with AHF |  | 48 hours | 
| To assess the safety and tolerability of 3 dose levels of IV omecamtiv mecarbil compared with placebo in subjects with left ventricular systolic dysfunction hospitalized for acute heart failure |  | 48 hours | 
| To evaluate the effects of 48 hours treatment with IV omecamtiv mecarbil on additional measures of dyspnea, patient global assessment (PGA), change in NT-proBNP, incidence of worsening heart failure, and short term clinical outcomes |  | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravenous, IV, Left Ventricular Systolic Dysfunction, Hospitalized, Acute heart failure, Heart failure, Left ventricular ejection fraction, pharmacokinetics, Pharmacodynamics, Dyspnea, hospitalization, In-patient, Omecamtiv mecarbil, Double-blind, Randomized, Placebo-controlled