TerminatedNCT02291237LIBERTY-HCMUpdated Sep 24, 2018Results posted

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

A Phase 2/3 interventional study of Eleclazine and Placebo in Hypertrophic Cardiomyopathy, sponsored by Gilead Sciences. Terminated at 46 sites in 8 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-09-24.

Sponsored by Gilead Sciences · Phase 2/3, Interventional, and Treatment

Phase: Phase 2/3
Study type: Interventional
Enrollment: 172
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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 studied

Hypertrophic Cardiomyopathy

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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

In context

Cardiomyopathies

1,176 studies on the registry are indexed under Cardiomyopathies; 287 are open to participants now.

This study's enrollment of 172 is above the median of 51 across 609 interventional studies indexed under Cardiomyopathies.

Browse Cardiomyopathies studies →

Lead sponsor

Gilead Sciences is the lead sponsor of 680 studies on the registry; 24 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 249 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Key Inclusion Criteria:

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)

Key Exclusion Criteria:

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design

Phase: Phase 2 / Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 172 participants (actual)

Study arms

Experimental
Eleclazine
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
Experimental
Placebo
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

DrugEleclazine
Tablet (s) administered orally once daily
Also known as: GS-6615
DrugPlacebo
Placebo to match eleclazine administered orally once daily

What researchers measure

Primary outcomes

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

Secondary outcomes

Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12
Time frame: Baseline to Week 12
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24
The MLHFQ is a 21-item quality of life (QoL) questionnaire that measures the effects of symptoms, functional limitations, and psychological distress on an individual. Each item is measured on a 6-point Likert scale (0 to 5) and is scored by summing the responses to all 21 questions. Scores range from 0 to 105, with lower scores indicating a better quality of life.
Time frame: Baseline to Week 24
Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12
The MLHFQ is a 21-item quality of life (QoL) questionnaire that measures the effects of symptoms, functional limitations, and psychological distress on an individual. Each item is measured on a 6-point Likert scale (0 to 5) and is scored by summing the responses to all 21 questions. Scores range from 0 to 105, with lower scores indicating a better quality of life.
Time frame: Baseline to Week 12
Change in Treadmill Exercise Time From Baseline to Week 24
Treadmill exercise time is the time to peak exercise.
Time frame: Baseline to Week 24
Change in Treadmill Exercise Time From Baseline to Week 12
Treadmill exercise time is the time to peak exercise.
Time frame: Baseline to Week 12

Results

Posted Mar 22, 2018

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.

Participant flow

Participants were enrolled at study sites in Asia, Australia, Europe and North America. The first participant was screened on 05 February 2015. The last study visit occurred on 22 February 2017.

Participant flow — Overall Study
Milestone	Eleclazine 30/3/6 mg	Placebo
Started	86	86
Completed	0	0
Not completed	86	86
Withdrew: Study terminated by sponsor	72	67
Withdrew: Adverse event	1	3
Withdrew: Investigator's discretion	0	3
Withdrew: Withdrew consent	11	11
Withdrew: Lost to follow-up	0	2
Withdrew: Subject required prohibited medication	2	0

Outcome measures

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

Time frame:: Baseline to Week 24
Reported as:: Mean · mL/kg/min

Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24
mL/kg/min	Eleclazine 30/3/6 mg	Placebo
Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24	0.15 ± 4.312	0.48 ± 4.143

Statistical analysis

Eleclazine 30/3/6 mg vs Placebo · ANCOVA · p = 0.416 · Ls mean difference(eleclazine - placebo): -0.55 · 95% CI -1.87 to 0.78P-value and Least Squares (LS) Means are from model with terms for sex, age (continuous), and treatment group and baseline peak VO2 as the covariate.

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

Time frame:: Baseline to Week 12
Reported as:: Mean · mL/kg/min

Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12
mL/kg/min	Eleclazine 30/3/6 mg	Placebo
Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12	0.28 ± 4.028	0.57 ± 4.314

Statistical analysis

Eleclazine 30/3/6 mg vs Placebo · ANCOVA · p = 0.517 (P-value and LS Means are from model with terms for sex, age (continuous), and treatment group and baseline peak VO2 as the covariate.) · Ls mean difference(eleclazine - placebo): -0.42 · 95% CI -1.68 to 0.85

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

The MLHFQ is a 21-item quality of life (QoL) questionnaire that measures the effects of symptoms, functional limitations, and psychological distress on an individual. Each item is measured on a 6-point Likert scale (0 to 5) and is scored by summing the responses to all 21 questions. Scores range from 0 to 105, with lower scores indicating a better quality of life.

Time frame:: Baseline to Week 24
Reported as:: Mean · Score

Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24
Score	Eleclazine 30/3/6 mg	Placebo
Baseline	40.22 ± 25.544	38.80 ± 23.177
Change from Baseline at Week 24	-4.05 ± 15.164	-5.57 ± 14.345

Statistical analysis

Eleclazine 30/3/6 mg vs Placebo · ANCOVA · p = 0.513 · Ls mean difference(eleclazine - placebo): 1.54 · 95% CI -3.11 to 6.19P-value and LS Means are from model with terms for sex, age (continuous), and treatment group and baseline score as the covariate.

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

Time frame:: Baseline to Week 12
Reported as:: Mean · Score

Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12
Score	Eleclazine 30/3/6 mg	Placebo
Baseline	40.22 ± 25.544	38.80 ± 23.177
Change at Week 12	-3.84 ± 15.654	-3.40 ± 13.780

Statistical analysis

Eleclazine 30/3/6 mg vs Placebo · ANCOVA · p = 0.964 · Ls mean difference(eleclazine - placebo): 0.10 · 95% CI -4.36 to 4.56P-value and LS Means are from model with terms for sex, age (continuous), and treatment group and baseline score as the covariate.

SecondaryChange in Treadmill Exercise Time From Baseline to Week 24

Treadmill exercise time is the time to peak exercise.

Time frame:: Baseline to Week 24
Reported as:: Mean · min

Change in Treadmill Exercise Time From Baseline to Week 24
min	Eleclazine 30/3/6 mg	Placebo
Baseline	12.88 ± 4.641	13.60 ± 4.317
Change from Baseline at Week 24	0.27 ± 3.954	0.24 ± 3.208

Statistical analysis

Eleclazine 30/3/6 mg vs Placebo · ANCOVA · p = 0.944 · Ls mean difference(eleclazine - placebo): -0.04 · 95% CI -1.18 to 1.10P-value and LS Means are from model with terms for sex, age (continuous), and treatment group and baseline score as the covariate.

SecondaryChange in Treadmill Exercise Time From Baseline to Week 12

Treadmill exercise time is the time to peak exercise.

Time frame:: Baseline to Week 12
Reported as:: Mean · min

Change in Treadmill Exercise Time From Baseline to Week 12
min	Eleclazine 30/3/6 mg	Placebo
Baseline	12.88 ± 4.641	13.60 ± 4.317
Change from Baseline at Week 12	0.48 ± 3.295	0.38 ± 3.030

Statistical analysis

Eleclazine 30/3/6 mg vs Placebo · ANCOVA · p = 0.993 · Ls mean difference(eleclazine - placebo): 0.00 · 95% CI -0.96 to 0.97P-value and LS Means are from model with terms for sex, age (continuous), and treatment group and baseline score as the covariate.

Adverse events

Collected over Baseline up to the last dose date plus 30 days (maximum exposure: 668 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Eleclazine 30/3/6 mg	0/86 (0%)	14/86 (16.3%)	58/86 (67.4%)
Placebo	0/86 (0%)	16/86 (18.6%)	62/86 (72.1%)

Most frequent serious events

Showing 10 of 40

Most frequent serious events
Event	Eleclazine 30/3/6 mg	Placebo
VENTRICULAR TACHYCARDIACardiac disorders	0/86	3/86
ATRIAL FIBRILLATIONCardiac disorders	2/86	1/86
CARDIAC FAILURE CONGESTIVECardiac disorders	2/86	0/86
CHEST PAINGeneral disorders	2/86	2/86
DEVICE RELATED INFECTIONInfections and infestations	2/86	0/86
ATRIAL FLUTTERCardiac disorders	1/86	0/86
CARDIAC FAILURECardiac disorders	1/86	0/86
CARDIAC FAILURE ACUTECardiac disorders	1/86	0/86
SINUS BRADYCARDIACardiac disorders	0/86	1/86
HYPERTROPHIC CARDIOMYOPATHYCongenital, familial and genetic disorders	0/86	1/86

Most frequent other events

Showing 10 of 22

Most frequent other events
Event	Eleclazine 30/3/6 mg	Placebo
DYSPNOEARespiratory, thoracic and mediastinal disorders	16/86	8/86
DIZZINESSNervous system disorders	12/86	14/86
PALPITATIONSCardiac disorders	9/86	11/86
NAUSEAGastrointestinal disorders	11/86	11/86
CHEST PAINGeneral disorders	11/86	9/86
NASOPHARYNGITISInfections and infestations	5/86	11/86
HEADACHENervous system disorders	11/86	11/86
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations	7/86	10/86
FATIGUEGeneral disorders	9/86	7/86
BACK PAINMusculoskeletal and connective tissue disorders	9/86	6/86

Baseline characteristics

Safety Analysis Set: all randomized participants who received at least 1 dose of study drug

Age, Continuous
Age, Continuous(years)	Eleclazine 30/3/6 mg	Placebo	Total
Mean	46 ± 11.7	48 ± 10.3	47 ± 11.1

Sex: Female, Male
Sex: Female, Male(Participants)	Eleclazine 30/3/6 mg	Placebo	Total
Female	37	36	73
Male	49	50	99

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Eleclazine 30/3/6 mg	Placebo	Total
White	74	73	147
Black or African American	7	3	10
Asian	2	7	9
Other	2	1	3
Not Permitted	0	2	2
American Indian or Alaska Native	1	0	1

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Eleclazine 30/3/6 mg	Placebo	Total
Hispanic Or Latino	11	9	20
Not Hispanic Or Latino	75	75	150
Not Permitted	0	2	2

Region of Enrollment
Region of Enrollment(participants)	Eleclazine 30/3/6 mg	Placebo	Total
United States	55	54	109
Australia	1	1	2
France	3	5	8
Germany	2	2	4
Israel	8	6	14
Italy	12	13	25
Netherlands	2	5	7
United Kingdom	3	0	3

Peak Oxygen Intake (VO2)
Peak Oxygen Intake (VO2)(mL/kg/min)	Eleclazine 30/3/6 mg	Placebo	Total
Mean	19.06 ± 4.853	19.88 ± 4.645	19.47 ± 4.755

Study locations

46 sites

Cedars-Sinai Heart Institute
Los Angeles, California, United States
University of California Los Angeles
Los Angeles, California, United States
Stanford University
Stanford, California, United States
Yale New Haven Hospital
New Haven, Connecticut, United States
Athens Regional Medical Center
Athens, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Brigham & Women's Hospital and Harvard Medical School
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Tufts Medical Center
Boston, Massachusetts, United States
Washington University School of Medicine
Saint Louis, Missouri, United States
Morristown Medical Center
Morristown, New Jersey, United States
Columbia University Medical Center/ New York Presbyterian
New York, New York, United States
NYU School of Medicine Pediatrics
New York, New York, United States
Duke Health Center at Southpoint
Durham, North Carolina, United States
Oregon Health and Science University
Portland, Oregon, United States
St. Luke's University Health Network
Bethlehem, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
St. Thomas Research Institute
Nashville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Houston Methodist Hospital
Houston, Texas, United States
Texas Heart Institute
Houston, Texas, United States
UT Southwestern Medical Center
Houston, Texas, United States
University of Washington
Seattle, Washington, United States
Marshfield Clinic Research Institute
Marshfield, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
The Alfred Hospital
Melbourne, Victoria, Australia
Hôpital Européen Georges Pompidou
Paris, France
Universitätsklinikum Hamburg Eppendorf
Hamburg, Germany
Ein Kerem-Hadassah Medical Organization
Jerusalem, Israel
Rabin Medical Center
Petah Tikva, Israel
Sheba Medical Center
Ramat-Gan, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Madonna del Soccorso Hospital
San Benedetto del Tronto, Ascoli Piceno, Italy
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, Italy
Azienda Ospedaliero Universitaria Di Bologna
Bologna, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, Italy
Ospedale San Raffaele S.r.l.
Milan, Italy
Azienda Ospedaliera Monaldi
Naples, Italy
Azienda Ospedaliero Universitaria di Parma
Parma, Italy
Azienda Ospedaliera San Camillo Forlanini
Rome, Italy
Academisch Medisch Centrum Amsterdam
Amsterdam, Noord-Holland, Netherlands
Erasmus MC
Rotterdam, Netherlands
University Medical Center Utrecht
Utrecht, Netherlands
University Hospital of Wales
Cardiff, South Glamergon, United Kingdom
Northern General Hospital
Sheffield, Yorkshire, United Kingdom

References and documents

Publications

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. PubMed 26915375 ↗

Study documents

Study protocol · Apr 1, 2014
Study protocol · Oct 10, 2014
Study protocol · Feb 10, 2015
Study protocol · Aug 12, 2016
Statistical analysis plan · May 10, 2017

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 24, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02291237
Lead sponsor: Gilead Sciences
Responsible party: Sponsor
First posted: Nov 14, 2014
Start date: Feb 5, 2015
Primary completion: Jan 20, 2017
Completion: Feb 17, 2017
Results posted: Mar 22, 2018
Last update: Sep 24, 2018

Study contacts

Gilead Study Director

study director · Gilead Sciences

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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