Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure

NCT ID: NCT03759392

Last Updated: 2023-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-09
• Study Completion Date: 2022-01-06

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

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

Conditions

Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Omecamtiv Mecarbil

Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.

Group Type: EXPERIMENTAL

Omecamtiv Mecarbil

Intervention Type: DRUG

Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing

Placebo

Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral placebo twice daily for up to 20 weeks

Interventions

Omecamtiv Mecarbil

Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing

Intervention Type: DRUG

Placebo

Oral placebo twice daily for up to 20 weeks

Intervention Type: DRUG

Other Intervention Names

CK-1827452; AMG-423

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cytokinetics, MD

Role: STUDY_DIRECTOR

Cytokinetics

Locations

Alaska Heart and Vascular Institute

Anchorage, Alaska, United States

Arkansas Cardiology Clinic

Little Rock, Arkansas, United States

Harbor-UCLA Medical Center

Torrance, California, United States

South Denver Cardiology Associates, PC

Littleton, Colorado, United States

Hartford Hospital-University of Connecticut School of Medicine

Hartford, Connecticut, United States

Holy Cross Hospital - Fort Lauderdale

Fort Lauderdale, Florida, United States

Broward Research Center - Pembroke Pines

Pembroke Pines, Florida, United States

Emory University

Atlanta, Georgia, United States

Community Hospital South, Inc.

Indianapolis, Indiana, United States

Saint Vincent Medical Group Inc.

Indianapolis, Indiana, United States

University of Maryland

Baltimore, Maryland, United States

Massachusetts General Hospital (MGH) - Cardiac Unit Associates

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Heart & Vascular Institute

Detroit, Michigan, United States

McLaren Health Care Corporation

Petoskey, Michigan, United States

Michigan Heart

Ypsilanti, Michigan, United States

Saint Luke's Health System

Kansas City, Missouri, United States

Glacier View Research Institute, Cardiology

Kalispell, Montana, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Cardiovascular Associates Of The Delaware Valley (Cadv), P.A. - Elmer Physicians Care Center - Elmer

Elmer, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

NYU Langone Medical Center

New York, New York, United States

Queens Heart Institute

Rosedale, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Med Health and Hospital

Raleigh, North Carolina, United States

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

The Ohio State University

Columbus, Ohio, United States

St. John Clinical Research Institute

Tulsa, Oklahoma, United States

Oregon Health

Portland, Oregon, United States

Capital Area Research, LLC

Camp Hill, Pennsylvania, United States

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, United States

Lancaster Heart And Stroke Foundation

Lancaster, Pennsylvania, United States

Greenville Health System

Greenville, South Carolina, United States

University of Texas - Southwestern Medical Center

Dallas, Texas, United States

Baylor Scott and White Heart and Vascular Hospital

Dallas, Texas, United States

Inova Heart and Vascular Institute

Falls Church, Virginia, United States

Foothills Medical Centre

Calgary, Alberta, Canada

London Health Sciences Centre - University Hospital

London, Ontario, Canada

Ecogene-21

Chicoutimi, Quebec, Canada

Universite de Montreal Institut de Cardiologie de Montreal ICM Montreal Heart Institute MHI

Montreal, Quebec, Canada

Mcgill University Health Centre (MUHC)-The Montreal General Hospital (MGH)

Montreal, Quebec, Canada

Centre Hospitalier De La Cote Basque

Bayonne, , France

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, , France

Centre Hospitalier Universitaire de Grenoble-Hopital Albert Michallon

La Tronche, , France

Universite De Nantes - L'Institut Du Thorax

Nantes, , France

Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Lariboisiere

Paris, , France

Chu de Rouen Hopital Charles Nicolle

Rouen, , France

Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil

Toulouse, , France

Universitaetsklinik Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Universitatsklinikum Magdeburg

Magdeburg, Saxony-Anhalt, Germany

Universitaetsklinikum Jena

Jena, Thuringia, Germany

Kerckhoff-Klinik- Bad Nauheim

Bad Nauheim, , Germany

Praxisklinik Dresden

Dresden, , Germany

Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes

Homburg, , Germany

Balatonfuredi Allami Szivkorhaz

Balatonfüred, , Hungary

Semmelweis University Heart and Vascular Center

Budapest, , Hungary

Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)

Pécs, , Hungary

Ospedali Riuniti Foggia

Foggia, Apulia, Italy

Centro Cardiologico Monzino IRCCS

Milan, Lombardy, Italy

Azienda Ospedaliera S.Orsola Malpighi

Bologna, Province of Bologna, Italy

Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia

Brescia, Province Of Brescia, Italy

Insituto Di Ricovero E Cura A Carattere Scientifico San Raffaele Pisana

Roma, Rome, Italy

Divisione di Cardiologia con Utic ed Emodinamica

Napoli, , Italy

Ospedale Monaldi

Napoli, , Italy

Erasmus MC - Universitair Medisch Centrum Rotterdam

Rotterdam, South Holland, Netherlands

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Onze Lieve Vrouwe Gasthuis (OLVG) Locatie West

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc)

Nijmegen, , Netherlands

Universitair Medisch Centrum Utrecht - Wilhelmina Kinderziekenhuis

Utrecht, , Netherlands

Maxima Medisch Centrum Veldhoven

Veldhoven, , Netherlands

Centrum Medyczne Medyk Sp z o.o. Sp. k.

Rzeszów, Podkarpackie Voivodeship, Poland

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

Uniwersyteckie Centrum Kliniczne Kliniczne Centrum Kardiologii

Gdansk, , Poland

Oddzial Kliniczny Choroby Wiencowej i Niewydolnosci Serca z Pododdzialem Intensywnego Nadzoru Kardiologicznego

Krakow, , Poland

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika, Oddzial Kardiologiczny

Lodz, , Poland

Instytut Kardiologii Heart Failure Clinic

Warsaw, , Poland

Centrum Chorob Serca, Uniwersytecki Szpital Kllniczny im. Jana Mikulicza Radeckiego we Wrociawiu

Wroclaw, , Poland

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Enhet Klinisk forskning, hjartmedicin, Skanes Universitet Sjukhus

Lund, , Sweden

Countries

United States; Canada; France; Germany; Hungary; Italy; Netherlands; Poland; Sweden

References

Lewis GD, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, Ezekowitz JA, Bohm M, Teerlink JR, Docherty KF, Lopes RD, Divanji PH, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Felker GM. Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure With Reduced Ejection Fraction: The METEORIC-HF Randomized Clinical Trial. JAMA. 2022 Jul 19;328(3):259-269. doi: 10.1001/jama.2022.11016.

Reference Type: DERIVED

PMID: 35852527 (View on PubMed)

Lewis GD, Docherty KF, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, Ezekowitz JA, Ponikowski P, Bohm M, Teerlink JR, Heitner SB, Kupfer S, Malik FI, Meng L, Felker GM. Developments in Exercise Capacity Assessment in Heart Failure Clinical Trials and the Rationale for the Design of METEORIC-HF. Circ Heart Fail. 2022 May;15(5):e008970. doi: 10.1161/CIRCHEARTFAILURE.121.008970. Epub 2022 Mar 3.

Reference Type: DERIVED

PMID: 35236099 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001233-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CY 1031

Identifier Type: -

Identifier Source: org_study_id