Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure (METEORIC-HF)

• Sponsor: Amgen
• Collaborators: Cytokinetics; Servier
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

The purpose of this study is to evaluate the effect of treatment with omecamtiv mecarbil compared with placebo on exercise capacity as determined by cardiopulmonary exercise testing following 20 weeks of treatment with omecamtiv mecarbil or placebo

Condition or disease	Intervention/treatment	Phase
Heart Failure With Reduced Ejection Fraction	Drug: Omecamtiv Mecarbil; Drug: Placebo	Phase 3

Detailed Description:

Oversight Authorities:

United States: Food and Drug Administration Canada: Health Canada France: National Agency for the Safety of Medicine and Health Products Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy and Nutrition Italy: Italian Medicines Agency Netherlands: Medicines Evaluation Board Poland: Chief Pharmaceutical Inspectorate Sweden: Medical Products Agency

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	270 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure With Reduced Ejection Fraction and Decreased Exercise Tolerance
Estimated Study Start Date :	March 29, 2019
Estimated Primary Completion Date :	February 15, 2021
Estimated Study Completion Date :	March 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Omecamtiv Mecarbil	Drug: Omecamtiv Mecarbil; Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing
Placebo Comparator: Placebo	Drug: Placebo; Oral placebo twice daily for up to 20 weeks

Outcome Measures

Primary Outcome Measures :

1. Change in peak oxygen uptake (VO2) on cardiopulmonary exercise testing from baseline to Week 20 [ Time Frame: Week 20 ]

Secondary Outcome Measures :

1. Change in exercise capacity, as measured by the change in total workload during cardiopulmonary exercise testing (CPET) from baseline to Week 20 [ Time Frame: Week 20 ]
2. Change in ventilatory efficiency, as measured by the change in Ventilation (VE)/Carbon dioxide output (VCO2) slope during cardiopulmonary exercise testing (CPET) from baseline to Week 20 [ Time Frame: Week 20 ]
3. Change in the average daily activity units measured over a 2-week period from baseline (Week -2 to Day 1) to Week 18-20 [ Time Frame: Week 20 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

• Male or female, greater than or equal to 18 to lesser than or equal to 85 years of age
• History of chronic HF, defined as requiring continuous treatment with medications for HF for a minimum of 3 months before screening
• New York Heart Association (NYHA) class II or III at screening
• Left ventricular ejection fraction less than or equal to 35%
• On maximally tolerated HF standard of care (SoC) therapies consistent with regional clinical practice guidelines, if not contraindicated and according to investigator judgment of the subject's clinical status. Beta blocker dose must be stable for 30 days prior to randomization.
• N-terminal (NT)-proBNP level greater than or equal to 200 pg/mL
• Peak VO2 less than or equal to 75% of the predicted normal value with respiratory exchange ratio (RER) greater than or equal to 1.05 on a screening CPET, confirmed by a CPET core laboratory

Exclusion Criteria

• Severe uncorrected valvular heart disease
• Paroxysmal atrial fibrillation or flutter documented within the previous 6 months, direct-current (DC) cardioversion or ablation procedure for atrial fibrillation within 6 months, or plan to attempt to restore sinus rhythm within 6 months of randomization. Subjects with persistent atrial fibrillation and no sinus rhythm documented in the prior 6 months are permitted.
• Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart block without a pacemaker.
• History of gastrointestinal bleeding requiring hospitalization, urgent procedure or transfusion in the prior year, or received intravenous (IV) iron, blood transfusion, or an erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or planned blood transfusion or ESA use during the study screening or treatment period. Chronic, stable use of oral iron is permitted.
• Ongoing or planned enrollment in cardiac rehabilitation.
• Requires assistance to walk or use of mobility assistive devices such as motorized devices, wheelchairs, or walkers. The use of canes for stability while ambulating is acceptable if the subject is deemed capable of performing CPET.
• Major medical event or procedure within 3 months prior to randomization, including: hospitalization, surgery, renal replacement therapy or cardiac procedure. This includes episodes of decompensated HF that require IV HF treatment.
• At screening: Resting systolic BP greater than 140 mmHg or less than 85 mmHg, or diastolic BP greater than 90 mmHg (mean of triplicate readings); Resting heart rate greater than 90 beats per minute, or less than 50 beats per minute (mean of triplicate readings); Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 (by the modified Modification of Diet in Renal Disease equation); Hepatic impairment defined by a total bilirubin (TBL) greater than or equal to 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times ULN. Patients with documented Gilbert syndrome and TBL greater than or equal to 2 times ULN due to unconjugated hyperbilirubinemia, without other hepatic impairment, are permitted.
• Room air oxygen saturation under 90% at screening
• Hemoglobin less than 10.0 g/dL at screening
• Significant adverse finding (e.g., exercise-induced early ischemic changes, abnormal decrease in BP [systolic BP falls by more than 10 mmHg], unexpected arrhythmia or other serious finding) during CPET at screening that precludes safe participation in the study, per investigator
• Chronotropic incompetence (including inadequate pacemaker rate response) during CPET at screening, defined as a maximum heart rate <60% of the maximum predicted heart rate

Contacts and Locations

Contacts

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Contact: Amgen Call Center	866-572-6436	medinfo@amgen.com

Sponsors and Collaborators

Amgen

Cytokinetics

Servier

Investigators

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Study Director:	MD	Amgen

More Information

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Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT03759392 History of Changes
Other Study ID Numbers:	CY 1031; 2018-001233-40 ( EudraCT Number )
First Posted:	November 30, 2018
Last Update Posted:	March 13, 2019
Last Verified:	March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials:	Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
Time Frame:	Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria:	Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL:	http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

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Heart Failure; Heart Diseases; Cardiovascular Diseases