Aficamten Compared to Metoprolol in Symptomatic Obstructive Hypertophic Cardiomyopathy

What is the Purpose of this Study?

The purpose of this study is to compare the effectiveness and potential side effects of an investigational drug called aficamten with the beta-blocker, metoprolol, in people with obstructive hypertrophic cardiomyopathy (oHCM). Obstructive HCM is a condition in which the heart muscle becomes abnormally thickened, which can block the blood flow out of the heart, and the heart muscle works harder to pump blood to the body (increased heart pumping function). Aficamten is designed to reduce heart pumping function. Researchers aim to determine whether aficamten works better than metoprolol in reducing abnormal heart pumping. The effectiveness of both medicines will be compared by measuring participants’ ability to exercise, heart failure symptoms, and the structure of the heart via echocardiogram. Participants will be randomly assigned to receive either aficamten or metoprolol for a total of 24 weeks. They will also be asked to provide biological samples (such as blood or urine). Additionally, researchers will measure the amount of aficamten in the blood at various times, as well as the effect the drug may have on the patient’s oHCM.

Eligibility

* Participants who meet all the following criteria at screening may be included in the trial:
* Males and females between 18 to 85 years of age, inclusive, at screening
* Body mass index \< 35 kg/m2

Inclusion Criteria:

* Participants who meet all the following criteria at screening may be included in the trial:
* Males and females between 18 to 85 years of age, inclusive, at screening
* Body mass index \< 35 kg/m2
* Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography -
* Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and
* Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory:
1. ≥ 15 mm in one or more myocardial segments OR
2. ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM
* NYHA class II or III
* Has a screening echocardiogram with the following determined by the echocardiography core laboratory:
* Resting LVOT-G \> 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND
* LVEF ≥ 60%
* Hemoglobin ≥ 10g/dL
* Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks

Exclusion Criteria:

* Any of the following criteria will exclude potential participants from the trial:
* Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM
* History of intolerance or medical contraindication to beta blocker therapy
* Resting SBP of \> 160 mmHg
* Resting heart rate of \> 100 bpm
* Significant valvular heart disease
1. Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
2. Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment)
* Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
* History of LV systolic dysfunction (LVEF \< 45%) or stress cardiomyopathy at any time during their clinical course
* Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
* Documented room air oxygen saturation reading \< 90% at screening
* Planned septal reduction treatment that cannot be deferred during the trial period
* History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening
* History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed.
* Current or recent (\< 4 weeks) therapy with disopyramide
* History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
* Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten

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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 Metoprolol in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy; CY 6032

Study Details

Disease Type/Condition

Other

Principal Investigator

Rader, Florian

Age Group

Adult

Phase

III

IRB Number

STUDY00002482

ClinicalTrials.gov ID

NCT05767346

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org