Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
Conditions
Keywords
CK-3773274, CK-274, Aficamten, Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy, nHCM, ACACIA-HCM, ACACIA
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.
Interventions
DRUGAficamten
Oral Tablet
DRUGPlacebo
Oral Tablet
Sponsors
Cytokinetics
Sanofi
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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 ≤ 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Change in pVO2 | Baseline to Week 36 | Effect of aficamten compared with placebo on maximal exercise capacity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 New York Heart Association (NYHA) Functional Class | Baseline to Week 36 | Effect of aficamten compared with placebo on NYHA Functional Classification |
| Change in N-terminal prohormone brain natriuretic peptide (NT-proBNP) | Baseline to Week 36 | Effect of aficamten compared with placebo on a biomarker of cardiac wall stress |
| Change in Left Atrial Volume Index (LAVI) in participants without atrial fibrillation or flutter at baseline on ECG | Baseline to Week 36 | Effect of aficamten compared with placebo on echocardiographic measures of structural remodeling |
| Time to first cardiovascular (CV) event | Baseline to End of Study, Week 72 | Effect of aficamten compared with placebo on cardiovascular events (ie, CV 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) |
Countries
Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, Greece, Hungary, Iceland, Israel, Italy, Japan, Netherlands, Poland, Portugal, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORCytokinetics MD
Cytokinetics
Outcome results
None listed