A study of aficamten (CK-3773274) in adults with symptomatic non-obstructive hypertrophic cardiomyopathy (ACACIA)
- Conditions
- SYMPTOMATIC NON-OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHYMedDRA version: 20.0Level: PTClassification code: 10020871Term: Hypertrophic cardiomyopathy Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- CTIS2023-505797-15-00
- Lead Sponsor
- Cytokinetics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 420
Between 18–85 years of age at screening, Body mass index < 40 kg/m2, Diagnosed with nHCM and has a screening echocardiogram with the following: • End-diastolic 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, New York Heart Association (NYHA) class II or III, Respiratory exchange ratio of = 1.00 at screening by CPET and predicted peak oxygen uptake (pVO2) of = 90% for age and sex, KCCQ-CSS score of = 30 and = 85, N-terminal prohormone brain natriuretic peptide (NT-proBNP) of: • = 300 pg/mL or = 900 pg/mL if in atrial fibrillation or atrial flutter OR • For Black participants, = 225 pg/mL or = 675 pg/mL if in atrial fibrillation or atrial flutter, Hemoglobin = 10 g/d
Significant valvular heart disease (per Investigator judgment) • Moderate or severe valvular aortic stenosis or fixed subaortic obstruction • Moderate or severe mitral regurgitation, 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, 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, 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), 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 the following events with exercise within 3 months prior to screening • syncope, • symptomatic ventricular arrhythmia, or • sustained ventricular tachyarrhythmia
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of aficamten compared with placebo on participant health status and maximal exercise capacity;Secondary Objective: To evaluate the effect of aficamten compared with placebo on maximal and sub-maximal exercise capacity, To evaluate the effect of aficamten compared with placebo on NYHA Functional Classification, To evaluate the effect of aficamten compared with placebo on a biomarker of cardiac wall stress, To evaluate the effect of aficamten compared with placebo on echocardiographic measures of structural remodeling, To evaluate the effect of aficamten compared with placebo on cardiovascular events;Primary end point(s): Primary: Change in KCCQ-CSS from baseline to Week 36 Co-primary: Change in pVO2 from baseline to Week 36
- Secondary Outcome Measures
Name Time Method Secondary end point(s):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;Secondary end point(s):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);Secondary end point(s):Proportion of participants with = 1 class improvement in NYHA Functional Class from baseline to Week 36;Secondary end point(s):Change in NT-proBNP from baseline to Week 36;Secondary end point(s):Change in LAVI from baseline to Week 36