ACACIA-HCM: The Purpose of This Study is to Evaluate the Efficacy and Safety of Aficamten (CK-3773274) Compared to Placebo in Adults With Symptomatic Non-obstructive Hypertrophic Cardiomyopathy

Sponsor

Cytokinetics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06081894

Collaborator

(none)

420

Enrollment

Locations

Arms

36.1

Anticipated Duration (Months)

210

Patients Per Site

5.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial will study the effects of aficamten (versus placebo) on the quality of life, exercise capacity, and clinical outcomes of patients with non-obstructive hypertrophic cardiomyopathy.

Condition or Disease	Intervention/Treatment	Phase
Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy	Drug: Aficamten Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

420 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Multi-Center, Randomized, Double-Blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

Actual Study Start Date :

Aug 30, 2023

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aficamten Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose levels guided by echocardiography assessments, for up to 72 weeks.	Drug: Aficamten Oral Tablet
Placebo Comparator: Placebo Participants in this arm will receive placebo, for up to 72 weeks.	Drug: Placebo Oral Tablet

Arm

Intervention/Treatment

Experimental: Aficamten

Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose levels guided by echocardiography assessments, for up to 72 weeks.

Drug: Aficamten

Oral Tablet

Placebo Comparator: Placebo

Participants in this arm will receive placebo, for up to 72 weeks.

Drug: Placebo

Oral Tablet

Outcome Measures

Primary Outcome Measures

Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [Baseline to Week 36]
Effect of aficamten compared with placebo on participant health status

Secondary Outcome Measures

Change in composite of two Z-scores of CPET parameters (pVO2 and VE/VCO2 slope) [Baseline to Week 36]
Effect of aficamten compared with placebo on global exercise capacity based on maximal and sub-maximal exercise performance
Proportion of participants with ≥ 1 class improvement in NYHA Functional Class [Baseline to Week 36]
Effect of aficamten compared with placebo on NYHA Functional Classification
Change in NT-proBNP [Baseline to Week 36]
Effect of aficamten compared with placebo on a biomarker of cardiac wall stress
Change in LAVI [Baseline to Week 36]
Effect of aficamten compared with placebo on echocardiographic measures of structural remodeling
Time to first CV event (CV death; heart transplantation or left ventricular assist device; aborted sudden cardiac death; non-fatal stroke; heart failure hospitalization; or cardiac arrhythmia requiring treatment or hospitalization) [Baseline to End of Study, Week 72]
Effect of aficamten compared with placebo on cardiovascular events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 18-85 years of age
Body mass index < 40 kg/m2
Diagnosed with nHCM and has a screening echocardiogram with the following:
End-diastolic left ventricular (LV) wall thickness:
≥ 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 AND
Resting LVOT-G < 30 mmHg AND Valsalva LVOT-G < 50 mmHg AND
LVEF ≥ 60%
Participants with a history of intracavitary obstruction are eligible.
NYHA class II or III
Respiratory exchange ratio of ≥ 1.00 at screening by cardiopulmonary exercise testing (CPET) and predicted peak oxygen uptake (pVO2) ≤ 90% for age and sex
KCCQ-CSS score of ≥ 30 and ≤ 85
NT-proBNP of:
NT-pro BNP ≥ 300 pg/mL or NT-proBNP ≥ 900 pg/mL if in atrial fibrillation or atrial flutter OR
For Black participants, an NT-pro BNP ≥ 225 pg/mL or NT-proBNP ≥ 675 pg/mL if in atrial fibrillation or atrial flutter

Exclusion Criteria:

Significant valvular heart disease (per Investigator judgment)
Moderate or severe valvular aortic stenosis or fixed subaortic obstruction
Moderate or severe mitral regurgitation
Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
Known current unrevascularized coronary artery stenosis of ≥ 70% or documented history of myocardial infarction.
History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy
Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
Documented room air oxygen saturation reading < 90% at screening or history of significant chronic obstructive pulmonary disease or severe/significant pulmonary hypertension
History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 3 months prior to screening
History of resistant hypertension (persistently elevated blood pressure despite maximal doses of 3 or more classes of medications for hypertension control)
Screening diastolic blood pressure ≥ 100 mmHg
Received prior treatment with aficamten
Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening)
Undergone septal reduction therapy < 6 months prior to screening
Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period
Paroxysmal or permanent atrial fibrillation is excluded only if:
rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 3 months prior to screening
rate control and anticoagulation have not been achieved for at least 3 months prior to screening.