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

• ClinicalTrials.gov Identifier: NCT02291237
• Recruitment Status: Terminated
• First Posted: November 14, 2014
• Results First Posted: March 22, 2018
• Last Update Posted: September 24, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: November 11, 2014
• First Posted Date: November 14, 2014
• Results First Submitted Date: January 19, 2018
• Results First Posted Date: March 22, 2018
• Last Update Posted Date: September 24, 2018
• Actual Study Start Date: February 5, 2015
• Actual Primary Completion Date: January 20, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 23, 2018): Change in Peak Oxygen Uptake (VO2) Achieved During Cardiopulmonary Exercise Testing (CPET) From Baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
• Original Primary Outcome Measures (submitted: November 11, 2014): Change in peak oxygen uptake (VO2) from baseline (screening) to Week 24 [ Time Frame: Up to 24 weeks ]

Current Secondary Outcome Measures (submitted: February 23, 2018)

• 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline to Week 24 ]
  Treadmill exercise time is the time to peak exercise.
• Change in Treadmill Exercise Time From Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
  Treadmill exercise time is the time to peak exercise.

Original Secondary Outcome Measures (submitted: November 11, 2014)

• Change in Minnesota Living With Heart Failure Questionnaire (MLHFQ) From Baseline to Week 24 [ Time Frame: Up to 24 weeks ]
• Change in Treadmill Exercise Time From Baseline to Week 24 [ Time Frame: Up to 24 weeks ]
• Change in Peak VO2 from baseline to Week 12 [ Time Frame: Up to 12 weeks ]
• Change in the MLHFQ from baseline to Week 12 [ Time Frame: Up to 12 weeks ]
• Change in Treadmill Exercise Time From Baseline to Week 12 [ Time Frame: Up to 12 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Eleclazine (GS-6615) on Exercise Capacity in Subjects With Symptomatic Hypertrophic Cardiomyopathy
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hypertrophic Cardiomyopathy

Intervention

• Drug: Eleclazine
  Tablet (s) administered orally once daily
  Other Name: GS-6615
• Drug: Placebo
  Placebo to match eleclazine administered orally once daily

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.
  Intervention: 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.
  Interventions:

  • Drug: Eleclazine
  • Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 23, 2016): 172
• Original Estimated Enrollment (submitted: November 11, 2014): 180
• Actual Study Completion Date: February 17, 2017
• Actual Primary Completion Date: January 20, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Israel, Italy, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT02291237
• Other Study ID Numbers: GS-US-361-1157; 2013-004429-97 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2018