Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM)

• Register: ClinicalTrials.gov
• Last refreshed on: 10 March 2025
• Main ID: NCT05186818
• Date of registration: 23/12/2021
• Prospective Registration: Yes
• Primary sponsor: Cytokinetics
• Public title: Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM) SEQUOIA-HCM
• Scientific 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
• Date of first enrolment: February 1, 2022
• Target sample size: 282
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT05186818
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

China, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States

Contacts

• Name: Cytokinetics MD
• Affiliation: Cytokinetics

Key inclusion & exclusion 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.


Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Obstructive Hypertrophic Cardiomyopathy (oHCM)

Intervention(s)

Drug: Aficamten (5 mg, 10 mg, 15 mg, and 20 mg)

Drug: Placebo to match aficamten

Primary Outcome(s)

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

Secondary Outcome(s)

Change in post-Valsalva left ventricular outflow tract gradients (LVOT-G) [Time Frame: Baseline to Week 12 and Week 24]

Change in total workload during CPET [Time Frame: Baseline to Week 24]

Proportion of patients with =1 class improvement in New York Heart Association (NYHA) Functional Class [Time Frame: Baseline to Week 12 and Week 24]

Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [Time Frame: Baseline to Week 12 and Week 24]

Duration of eligibility for septal reduction therapy (SRT) [Time Frame: Baseline to Week 24]

Proportion of patients with post-Valsalva LVOT G <30 mmHg [Time Frame: Baseline to Week 12 and Week 24]

Secondary ID(s)

CY 6031

2021-003536-92

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Corxel Pharmaceuticals