Effect of Eleclazine (GS-6615) on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy

NCT02291237 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-361-11572013-004429-97
• Study Type: interventional
• Target: 172
• Locations: 8 countries
• Sites: 46

Brief Summary

The primary objective of this study was to evaluate the effect of eleclazine (GS-6615) on exercise capacity as measured by Peak oxygen uptake (VO2) achieved during cardiopulmonary exercise testing (CPET), in participants with symptomatic hypertrophic cardiomyopathy (HCM).

Conditions

Hypertrophic Cardiomyopathy

Keywords

hypertrophic cardiomyopathy; hcm; hocm; hypertrophic myocardiopathy; hypertrophic obstructive cardiomyopathies; cardiomyopathy; hypertrophic; familial hypertrophic cardiomyopathy; genetic heart disease; echocardiography; cardiopulmonary exercise testing; exercise Capacity; heart failure; angina; dyspnea; diastolic dysfunction; microvascular ischemia; late sodium current inhibitor; GS-6615; late INA

Outcome Measures

Primary Outcomes (1)

• Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24

  Baseline to Week 24

Secondary Outcomes (5)

• Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12

  Baseline to Week 12

• Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24

  Baseline to Week 24

• Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12

  Baseline to Week 12

• Change in Treadmill Exercise Time From Baseline to Week 24

  Baseline to Week 24

• Change in Treadmill Exercise Time From Baseline to Week 12

  Baseline to Week 12

Study Arms (2)

Eleclazine

EXPERIMENTAL

Eleclazine 30 mg single loading dose followed by 3 mg daily maintenance dose up until Week 12, then 6 mg daily maintenance dose from Week 12 at least Week 24, followed by eleclazine 6 mg in an open-label extension period.

Drug: Eleclazine

Placebo

EXPERIMENTAL

Placebo to match eleclazine until at least Week 24, followed by active eleclazine 6 mg in an open-label extension period.

Drug: Eleclazine; Drug: Placebo

Interventions

Eleclazine DRUG

Tablet (s) administered orally once daily

Also known as: GS-6615

Eleclazine; Placebo

Placebo DRUG

Placebo to match eleclazine administered orally once daily

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Established diagnosis of hypertrophic cardiomyopathy defined by standard criteria as a maximal left ventricular wall thickness ≥ 15 mm at initial diagnosis
• Exertional symptoms including at least one of the following:
• New York Heart Association (NYHA) Class ≥ II dyspnea
• Canadian Cardiovascular Society (CCS) Class ≥ II angina
• Screening (baseline) peak VO2 \< 80% of predicted for age, sex, and weight
• Ability to perform an upright treadmill cardiopulmonary exercise test (CPET)

You may not qualify if:

• Known aortic valve stenosis (moderate or severe)
• Known coronary artery disease
• Left ventricular systolic dysfunction (ejection fraction \< 50%)
• Recent septal reduction procedure (ie, surgical myectomy or alcohol septal ablation) within six months prior to screening or such a procedure scheduled to occur during the study

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (46)

Cedars-Sinai Heart Institute

Los Angeles, California, United States

Location

University of California Los Angeles

Los Angeles, California, United States

Location

Stanford University

Stanford, California, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, United States

Location

Athens Regional Medical Center

Athens, Georgia, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Location

Brigham & Women's Hospital and Harvard Medical School

Boston, Massachusetts, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

Tufts Medical Center

Boston, Massachusetts, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

Morristown Medical Center

Morristown, New Jersey, United States

Location

Columbia University Medical Center/ New York Presbyterian

New York, New York, United States

Location

NYU School of Medicine Pediatrics

New York, New York, United States

Location

Duke Health Center at Southpoint

Durham, North Carolina, United States

Location

Oregon Health and Science University

Portland, Oregon, United States

Location

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Location

St. Thomas Research Institute

Nashville, Tennessee, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

Houston Methodist Hospital

Houston, Texas, United States

Location

Texas Heart Institute

Houston, Texas, United States

Location

UT Southwestern Medical Center

Houston, Texas, United States

Location

University of Washington

Seattle, Washington, United States

Location

Marshfield Clinic Research Institute

Marshfield, Wisconsin, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, Germany

Location

Ein Kerem-Hadassah Medical Organization

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Madonna del Soccorso Hospital

San Benedetto del Tronto, Ascoli Piceno, Italy

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Italy

Location

Azienda Ospedaliero Universitaria Di Bologna

Bologna, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Italy

Location

Ospedale San Raffaele S.r.l.

Milan, Italy

Location

Azienda Ospedaliera Monaldi

Naples, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Italy

Location

Academisch Medisch Centrum Amsterdam

Amsterdam, North Holland, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

University Hospital of Wales

Cardiff, South Glamergon, United Kingdom

Location

Northern General Hospital

Sheffield, Yorkshire, United Kingdom

Location

Related Publications (1)

• Olivotto I, Hellawell JL, Farzaneh-Far R, Blair C, Coppini R, Myers J, Belardinelli L, Maron MS. Novel Approach Targeting the Complex Pathophysiology of Hypertrophic Cardiomyopathy: The Impact of Late Sodium Current Inhibition on Exercise Capacity in Subjects with Symptomatic Hypertrophic Cardiomyopathy (LIBERTY-HCM) Trial. Circ Heart Fail. 2016 Mar;9(3):e002764. doi: 10.1161/CIRCHEARTFAILURE.115.002764.

  PMID: 26915375 BACKGROUND

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Cardiomyopathies; Hypertrophy; Cardiomyopathy, Hypertrophic, Familial; Heart Failure; Angina Pectoris; Dyspnea

Interventions

eleclazine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myocardial Ischemia; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory

Limitations and Caveats

The totality of the data did not support continuation of the eleclazine development program. So, this study was terminated prior to the end of the double-blind phase, and therefore no participants entered the open-label extension (OLE) period.

Results Point of Contact

• Title: Clinical Trial Disclosures & Data Transparency
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: November 14, 2014
• Study Start: February 5, 2015
• Primary Completion: January 20, 2017
• Study Completion: February 17, 2017
• Last Updated: September 24, 2018
• Results First Posted: March 22, 2018

Record last verified: 2018-02

Locations

GB (2); AU (1); IL (4); FR (1); DE (1); NL (3); US (26); IT (8)