Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM (SEQUOIA-HCM) (SEQUOIA-HCM)

• ClinicalTrials.gov Identifier: NCT05186818
• Recruitment Status: Completed
• First Posted: January 11, 2022
• Last Update Posted: January 8, 2024
• Sponsor: Cytokinetics
• Collaborator: Ji Xing Pharmaceuticals (Shanghai) Co., Ltd.
• Information provided by (Responsible Party): Cytokinetics

Tracking Information

• First Submitted Date: December 23, 2021
• First Posted Date: January 11, 2022
• Last Update Posted Date: January 8, 2024
• Actual Study Start Date: February 1, 2022
• Actual Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 23, 2021)

Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET) [ Time Frame: Baseline to Week 24 ]

Effect of CK-3773274 on exercise capacity in patients with symptomatic oHCM

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 20, 2023)

• Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on patient health status
• Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on NYHA Functional Classification
• Change in post-Valsalva left ventricular outflow tract gradients (LVOT-G) [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on post-Valsalva LVOT-G
• Proportion of patients with post-Valsalva LVOT G <30 mmHg [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on post-Valsalva LVOT-G
• Change in total workload during CPET [ Time Frame: Baseline to Week 24 ]
  Effect of CK-3773274 on exercise capacity
• Duration of eligibility for septal reduction therapy (SRT) [ Time Frame: Baseline to Week 24 ]
  Effect of CK-3773274 on duration of eligibility for septal reduction therapy

Original Secondary Outcome Measures (submitted: December 23, 2021)

• Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on patient health status
• Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on NYHA Functional Classification
• Change in post-Valsalva left ventricular outflow tract gradients (LVOT-G) [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on post-Valsalva LVOT-G
• Proportion of patients with post-Valsalva LVOT G <30 mmHg [ Time Frame: Baseline to Week 12 and Week 24 ]
  Effect of CK-3773274 on post-Valsalva LVOT-G
• Change in total workload during CPET [ Time Frame: Baseline to Week 24 ]
  Effect of CK-3773274 on exercise capacity

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

Descriptive Information

• Brief Title: Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM (SEQUOIA-HCM)
• Official Title: A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
• Brief Summary: The purpose of this study is to evaluate the efficacy and safety of aficamten (CK-3773274) in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Obstructive Hypertrophic Cardiomyopathy (oHCM)

Intervention

• Drug: CK-3773274 (5 mg, 10 mg, 15 mg and 20 mg)
  CK-3773274 tablets administered orally
• Drug: Placebo to match CK-3773274
  Placebo administered orally

Study Arms

• Experimental: CK-3773274 up to 20 mg
  Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 24 weeks
  Intervention: Drug: CK-3773274 (5 mg, 10 mg, 15 mg and 20 mg)
• Placebo Comparator: Placebo to match CK-3773274
  Patients will receive placebo for up to 24 weeks
  Intervention: Drug: Placebo to match CK-3773274

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 20, 2023): 282
• Original Estimated Enrollment (submitted: December 23, 2021): 270
• Actual Study Completion Date: December 1, 2023
• Actual Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Males and females between 18 and 85 years of age, inclusive, at screening.
• Body mass index <35 kg/m2.

• Diagnosed with HCM per the following criteria:

  • Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac disease and

  • Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory of:

    • ≥15 mm in one or more myocardial segments OR
    • ≥13 mm in one or more wall segments and a known-disease-causing gene mutation or positive family history of HCM
• Has resting LVOT-G ≥30 mmHg and post-Valsalva LVOT G ≥50 mmHg during screening as determined by the echocardiography core laboratory.
• LVEF ≥60% at screening as determined by the echocardiography core laboratory.
• NYHA Functional Class II or III at screening.
• Hemoglobin ≥10g/dL at screening.
• Respiratory exchange ratio (RER) ≥1.05 and pVO2 ≤90% predicted on the screening CPET per the core laboratory.
• Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for >6 weeks prior to randomization and anticipate remaining on the same medication regimen during the trial. Patients treated with disopyramide must also be concomitantly treated with a beta blocker and/or calcium channel blocker.

Key Exclusion Criteria:

• Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).

• Significant valvular heart disease (per investigator judgment).

  • Moderate-severe valvular aortic stenosis.
  • Moderate-severe mitral regurgitation not due to systolic anterior motion of the mitral valve.
• History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at any time during their clinical course.
• Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations).
• Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the trial period.
• Documented paroxysmal atrial fibrillation during the screening period.

• Paroxysmal or permanent atrial fibrillation is only excluded IF:

  • rhythm restoring treatment (eg, direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤6 months prior to screening.
  • rate control and anticoagulation have not been achieved for at least 6 months prior to screening.
• History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
• Has received prior treatment with CK-3773274 or mavacamten.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05186818
• Other Study ID Numbers: CY 6031; 2021-003536-92 ( 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
• Current Responsible Party: Cytokinetics
• Original Responsible Party: Same as current
• Current Study Sponsor: Cytokinetics
• Original Study Sponsor: Same as current
• Collaborators: Ji Xing Pharmaceuticals (Shanghai) Co., Ltd.

Investigators

• Study Director: Cytokinetics MD; Cytokinetics

• PRS Account: Cytokinetics
• Verification Date: January 2024