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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. (A study of aficamten in adults with symptomatic non-obstructive hypertrophic cardiomyopathy (ACACIA-HCM))

A study of aficamten (CK-3773274) in adults with symptomatic non-obstructive hypertrophic cardiomyopathy
(ACACIA-HCM)

Divanji Punagh

Cytokinetics, Inc.

4-1-3 Kyuutaromachi, Chuo-ku, Osaka, 541-0056, Japan

Japan-Chiken@iconplc.com

Clinical trial contact

ICON Clinical Research GK

4-1-3 Kyutaro-cho, Chuuou-ku, Osaka-city, Osaka, 541-0056, Japan

+81-6-4560-2001

Japan-Chiken@iconplc.com

Recruiting

May. 01, 2025

Interventional

non-randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- 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

- 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 (e.g, 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 (e.g., 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.

Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

Drug: Aficamten Oral Tablet
Drug: Placebo Oral Tablet
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.
Interventions:
Drug: Aficamten
Placebo Comparator: Placebo
Participants in this arm will receive placebo, for up to 72 weeks.
Interventions:
Drug: Placebo

Dual primary endpoints of:
- Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [Time Frame: Baseline to Week 36]
- Change in pVO2 from baseline to Week 36"

- Proportion of participants with >= 1 class improvement in NYHA Functional Class from baseline to Week 36
- Change in the composite of two Z-scores of CPET parameters from baseline to Week 36:
- pVO2 (maximal exercise capacity)
- VE/VCO2 slope (sub-maximal exercise capacity)
- Change in NT-proBNP from baseline to Week 36
- Change in LAVI from baseline to Week 36
- Time to first event of cardiovascular death, heart transplantation or left ventricular assist device, aborted sudden cardiac death, non-fatal stroke, heart failure hospitalization, or cardiac arrhythmia (atrial fibrillation or ventricular tachyarrhythmia) requiring treatment or hospitalization)

+81-3-3541-5151

Mar. 13, 2025

No

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