phase 3 trial to evaluate the efficacy and safety of aficamten compared to placebo in adults with symptomatic nhcm

Conditions: Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

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.


Eligibility criteria:
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.

Keywords: ck-3773274 ck-274 aficamten symptomatic non-obstructive hypertrophic cardiomyopathy nhcm acacia-hcm acacia