Aficamten Compared to Placebo in Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

What is the Purpose of this Study?

The purpose of this study is to compare the effects of an experimental drug called aficamten and placebo (inactive substance) on the exercise capacity and health status of patients with symptomatic, non-obstructive hypertrophic cardiomyopathy (nHCM). nHCM is typically a genetic condition in which the main pumping chamber of the heart (left ventricle) becomes abnormally thickened and stiff. The effectiveness of aficamten and placebo will be compared by measuring patients’ ability to exercise, heart failure symptoms, and structure of the heart, as well as questionnaires regarding the status of general health, nHCM symptoms, and quality of life. The safety and tolerability of aficamten at increasing dose levels will also be studied. All participants will eventually be eligible to receive the study drug.

Eligibility

* Between 18-85 years of age
* Body mass index \< 40 kg/m2
* Diagnosed with nHCM and has a screening echocardiogram with the following:

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.

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Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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

Study Details

Disease Type/Condition

Other

Principal Investigator

Rader, Florian

Age Group

Adult

Phase

III

IRB Number

STUDY00002841

ClinicalTrials.gov ID

NCT06081894

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org