Hypertrophic Cardiomyopathy
Conditions
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
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).
Interventions
DRUGEleclazine
Tablet (s) administered orally once daily
DRUGPlacebo
Placebo to match eleclazine administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24 | Baseline to Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12 | 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. |
| Change in Treadmill Exercise Time From Baseline to Week 24 | Baseline to Week 24 | Treadmill exercise time is the time to peak exercise. |
| Change in Treadmill Exercise Time From Baseline to Week 12 | Baseline to Week 12 | Treadmill exercise time is the time to peak exercise. |
Countries
Australia, France, Germany, Israel, Italy, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
264 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Eleclazine 30/3/6 mg Single loading dose of eleclazine 30 mg (5 x 6 mg tablets) on Day 1, followed by 3 mg (1 x 3 mg tablet) daily maintenance dose until Week 12, then 6 mg (2 x 3 mg tablets) daily maintenance dose from Week 12 to at least Week 24 | 86 |
| Placebo Placebo to match eleclazine administered orally for up to at least 24 weeks | 86 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Investigator's Discretion | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Study Terminated by Sponsor | 72 | 67 |
| Overall Study | Subject Required Prohibited Medication | 2 | 0 |
| Overall Study | Withdrew Consent | 11 | 11 |
Baseline characteristics
| Characteristic | Eleclazine 30/3/6 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 11.7 | 48 years STANDARD_DEVIATION 10.3 | 47 years STANDARD_DEVIATION 11.1 |
| Peak Oxygen Intake (VO2) | 19.06 mL/kg/min STANDARD_DEVIATION 4.853 | 19.88 mL/kg/min STANDARD_DEVIATION 4.645 | 19.47 mL/kg/min STANDARD_DEVIATION 4.755 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 7 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic Or Latino | 11 Participants | 9 Participants | 20 Participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 75 Participants | 75 Participants | 150 Participants |
| Race/Ethnicity, Customized Not Permitted | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 74 Participants | 73 Participants | 147 Participants |
| Region of Enrollment Australia | 1 participants | 1 participants | 2 participants |
| Region of Enrollment France | 3 participants | 5 participants | 8 participants |
| Region of Enrollment Germany | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Israel | 8 participants | 6 participants | 14 participants |
| Region of Enrollment Italy | 12 participants | 13 participants | 25 participants |
| Region of Enrollment Netherlands | 2 participants | 5 participants | 7 participants |
| Region of Enrollment United Kingdom | 3 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 55 participants | 54 participants | 109 participants |
| Sex: Female, Male Female | 37 Participants | 36 Participants | 73 Participants |
| Sex: Female, Male Male | 49 Participants | 50 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 86 |
| other Total, other adverse events | 58 / 86 | 62 / 86 |
| serious Total, serious adverse events | 14 / 86 | 16 / 86 |
Outcome results
Primary
Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24
Time frame: Baseline to Week 24
Population: Full Analysis Set: all randomized participants who received at least 1 dose of study drug. Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eleclazine 30/3/6 mg | Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24 | 0.15 mL/kg/min | Standard Deviation 4.312 |
| Placebo | Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24 | 0.48 mL/kg/min | Standard Deviation 4.143 |
Comparison: The analysis evaluated the change in Peak VO2 from baseline to Week 24 for the eleclazine group compared with that of the placebo group using analysis of covariance (ANCOVA) including terms for baseline Peak VO2, sex, and age (continuous).p-value: 0.41695% CI: [-1.87, 0.78]ANCOVA
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eleclazine 30/3/6 mg | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12 | Baseline | 40.22 Score | Standard Deviation 25.544 |
| Eleclazine 30/3/6 mg | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12 | Change at Week 12 | -3.84 Score | Standard Deviation 15.654 |
| Placebo | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12 | Baseline | 38.80 Score | Standard Deviation 23.177 |
| Placebo | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 12 | Change at Week 12 | -3.40 Score | Standard Deviation 13.78 |
Comparison: The analysis evaluated the change in MLHFQ from baseline to Week 12 for the eleclazine group compared with that of the placebo group using ANCOVA including terms for baseline treadmill exercise time, sex, and age (continuous).p-value: 0.96495% CI: [-4.36, 4.56]ANCOVA
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eleclazine 30/3/6 mg | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24 | Baseline | 40.22 Score | Standard Deviation 25.544 |
| Eleclazine 30/3/6 mg | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24 | Change from Baseline at Week 24 | -4.05 Score | Standard Deviation 15.164 |
| Placebo | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24 | Baseline | 38.80 Score | Standard Deviation 23.177 |
| Placebo | Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24 | Change from Baseline at Week 24 | -5.57 Score | Standard Deviation 14.345 |
Comparison: The analysis evaluated the change in MLHFQ from baseline to Week 24 for the eleclazine group compared with that of the placebo group using ANCOVA including terms for baseline treadmill exercise time, sex, and age (continuous).p-value: 0.51395% CI: [-3.11, 6.19]ANCOVA
Secondary
Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12
Time frame: Baseline to Week 12
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eleclazine 30/3/6 mg | Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12 | 0.28 mL/kg/min | Standard Deviation 4.028 |
| Placebo | Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 12 | 0.57 mL/kg/min | Standard Deviation 4.314 |
Comparison: The analysis evaluated the change in Peak VO2 from baseline to Week 12 for the eleclazine group compared with that of the placebo group using ANCOVA including terms for baseline Peak VO2, sex, and age (continuous).p-value: 0.51795% CI: [-1.68, 0.85]ANCOVA
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eleclazine 30/3/6 mg | Change in Treadmill Exercise Time From Baseline to Week 12 | Baseline | 12.88 min | Standard Deviation 4.641 |
| Eleclazine 30/3/6 mg | Change in Treadmill Exercise Time From Baseline to Week 12 | Change from Baseline at Week 12 | 0.48 min | Standard Deviation 3.295 |
| Placebo | Change in Treadmill Exercise Time From Baseline to Week 12 | Baseline | 13.60 min | Standard Deviation 4.317 |
| Placebo | Change in Treadmill Exercise Time From Baseline to Week 12 | Change from Baseline at Week 12 | 0.38 min | Standard Deviation 3.03 |
Comparison: The analysis evaluated the change in treadmill exercise time from baseline to Week 12 for the eleclazine group compared with that of the placebo group using ANCOVA including terms for baseline treadmill exercise time, sex, and age (continuous).p-value: 0.99395% CI: [-0.96, 0.97]ANCOVA
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eleclazine 30/3/6 mg | Change in Treadmill Exercise Time From Baseline to Week 24 | Baseline | 12.88 min | Standard Deviation 4.641 |
| Eleclazine 30/3/6 mg | Change in Treadmill Exercise Time From Baseline to Week 24 | Change from Baseline at Week 24 | 0.27 min | Standard Deviation 3.954 |
| Placebo | Change in Treadmill Exercise Time From Baseline to Week 24 | Baseline | 13.60 min | Standard Deviation 4.317 |
| Placebo | Change in Treadmill Exercise Time From Baseline to Week 24 | Change from Baseline at Week 24 | 0.24 min | Standard Deviation 3.208 |
Comparison: The analysis evaluated the change in treadmill exercise time from baseline to Week 24 for the eleclazine group compared with that of the placebo group using ANCOVA including terms for baseline treadmill exercise time, sex, and age (continuous).p-value: 0.94495% CI: [-1.18, 1.1]ANCOVA