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

Heart Failure With Reduced Ejection Fraction Clinical Trial

— METEORIC-HF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03759392
• Other study ID #: CY 1031
• Secondary ID: 2018-001233-40
• Status: Completed
• Phase: Phase 3
• Start date: April 9, 2019
• Est. completion date: January 6, 2022

Study information

• Verified date: February 2023
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: January 6, 2022
• Est. primary completion date: November 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• Omecamtiv Mecarbil
Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing
• Placebo
Oral placebo twice daily for up to 20 weeks

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	Mcgill University Health Centre (MUHC)-The Montreal General Hospital (MGH)	Montreal	Quebec
Canada	Universite de Montreal Institut de Cardiologie de Montreal ICM Montreal Heart Institute MHI	Montreal	Quebec
France	Centre Hospitalier De La Cote Basque	Bayonne cedex
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 CEDEX 1
France	Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Lariboisiere	Paris
France	Chu de Rouen Hopital Charles Nicolle	Rouen Cedex
France	Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil	Toulouse Cedex 9
Germany	Kerckhoff-Klinik- Bad Nauheim	Bad Nauheim
Germany	Praxisklinik Dresden	Dresden
Germany	Universitaetsklinik Heidelberg	Heidelberg	Baden-wurttemberg
Germany	Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes	Homburg
Germany	Universitaetsklinikum Jena	Jena	Thueringen
Germany	Universitatsklinikum Magdeburg	Magdeburg	Saxony-Anhalt
Hungary	Balatonfuredi Allami Szivkorhaz	Balatonfured
Hungary	Semmelweis University Heart and Vascular Center	Budapest
Hungary	Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)	Pecs
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	Ospedali Riuniti Foggia	Foggia	Apulia
Italy	Centro Cardiologico Monzino IRCCS	Milano	Lombardia
Italy	Divisione di Cardiologia con Utic ed Emodinamica	Napoli
Italy	Ospedale Monaldi	Napoli
Italy	Insituto Di Ricovero E Cura A Carattere Scientifico San Raffaele Pisana	Roma	Rome
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	Erasmus MC - Universitair Medisch Centrum Rotterdam	Rotterdam	South Holland
Netherlands	Universitair Medisch Centrum Utrecht - Wilhelmina Kinderziekenhuis	Utrecht
Netherlands	Maxima Medisch Centrum Veldhoven	Veldhoven
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	Centrum Medyczne Medyk Sp z o.o. Sp. k.	Rzeszow	Podkarpackie
Poland	Instytut Kardiologii Heart Failure Clinic	Warsaw
Poland	Centrum Chorob Serca, Uniwersytecki Szpital Kllniczny im. Jana Mikulicza Radeckiego we Wrociawiu	Wroclaw
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Enhet Klinisk forskning, hjartmedicin, Skanes Universitet Sjukhus	Lund
United States	Alaska Heart and Vascular Institute	Anchorage	Alaska
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Massachusetts General Hospital (MGH) - Cardiac Unit Associates	Boston	Massachusetts
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	The Ohio State University	Columbus	Ohio
United States	Baylor Scott and White Heart and Vascular Hospital	Dallas	Texas
United States	University of Texas - Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Heart & Vascular Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Cardiovascular Associates Of The Delaware Valley (Cadv), P.A. - Elmer Physicians Care Center - Elmer	Elmer	New Jersey
United States	Inova Heart and Vascular Institute	Falls Church	Virginia
United States	Holy Cross Hospital - Fort Lauderdale	Fort Lauderdale	Florida
United States	Greenville Health System	Greenville	South Carolina
United States	Hartford Hospital-University of Connecticut School of Medicine	Hartford	Connecticut
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Community Hospital South, Inc.	Indianapolis	Indiana
United States	Saint Vincent Medical Group Inc.	Indianapolis	Indiana
United States	Glacier View Research Institute, Cardiology	Kalispell	Montana
United States	Saint Luke's Health System	Kansas City	Missouri
United States	Lancaster Heart And Stroke Foundation	Lancaster	Pennsylvania
United States	Arkansas Cardiology Clinic	Little Rock	Arkansas
United States	South Denver Cardiology Associates, PC	Littleton	Colorado
United States	NYU Langone Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Broward Research Center - Pembroke Pines	Pembroke Pines	Florida
United States	McLaren Health Care Corporation	Petoskey	Michigan
United States	Oregon Health	Portland	Oregon
United States	Wake Med Health and Hospital	Raleigh	North Carolina
United States	Queens Heart Institute	Rosedale	New York
United States	Harbor-UCLA Medical Center	Torrance	California
United States	St. John Clinical Research Institute	Tulsa	Oklahoma
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina
United States	Michigan Heart	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20	The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.	Baseline and Week 20
Secondary	Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20	Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work.	Baseline and Week 20
Secondary	Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20	Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis.	Baseline and Week 20
Secondary	Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20	The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals.	Baseline (Week -2 to Day 1) to Weeks 18-20