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

Study Overview
=================
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).

Official Title
-----------------
Study Title: A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of GS-6615 on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy

Conditions
-----------------
Hypertrophic Cardiomyopathy

Intervention / Treatment
-----------------
* Drug: Eleclazine
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eleclazine<br>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<br>* Tablet (s) administered orally once daily<br>* Other names: GS-6615;|
| Experimental: Placebo<br>Placebo to match eleclazine until at least Week 24, followed by active eleclazine 6 mg in an open-label extension period. | Drug: Eleclazine<br>* Tablet (s) administered orally once daily<br>* Other names: GS-6615;Drug: Placebo<br>* Placebo to match eleclazine administered orally once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24 |  | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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. | Baseline to Week 12 | 
| Change in Treadmill Exercise Time From Baseline to Week 24 | Treadmill exercise time is the time to peak exercise. | Baseline to Week 24 | 
| Change in Treadmill Exercise Time From Baseline to Week 12 | Treadmill exercise time is the time to peak exercise. | Baseline to Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
angina, hcm, hypertrophic cardiomyopathy, hocm, hypertrophic myocardiopathy, hypertrophic obstructive cardiomyopathies, cardiomyopathy, hypertrophic, familial hypertrophic cardiomyopathy, genetic heart disease, echocardiography, cardiopulmonary exercise testing, exercise Capacity, heart failure, dyspnea, diastolic dysfunction, microvascular ischemia, late sodium current inhibitor, GS-6615, late INA