LEAF‑HCM: What can we learn from the early use of aficamten in people who have no symptoms but do have a thickened heart muscle with blood flow obstruction?

Trial details

Who runs it

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Trial code

EU 2025-523090-42-00

Record updated

2026. szeptember 29.

Original description

To evaluate the effect of aficamten vs placebo on post-Valsalva left ventricular outflow tract gradients (LVOT-G) in patients with asymptomatic oHCMRead full original descriptionShow less

Learning From Early Aficamten In HCM (LEAF-HCM)

To evaluate the effect of aficamten vs placebo on post-Valsalva left ventricular outflow tract gradients (LVOT-G) in patients with asymptomatic oHCM

Inclusion: Males and females between 18 and 70 years of age; Able to comprehend and willing to sign an ICF; Diagnosed with HCM per the following criteria: - Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac disease and - Has an end-diastolic LV wall thickness as measured by the screening cardiologist of: o ≥15 mm in one or more myocardial wall segments o ≥13mm in one or more myocardial wall segments and a known pathogenic/likely pathogenic genetic variant or positive family history of HCM; Resting LVOT-G ≥30 mmHg and/or post-Valsalva LVOT G ≥50 mmHg; LVEF ≥60%; New York Heart Association (NYHA) Functional Class I; BMI under 35kg/m2; Willing to comply with anticonception guidelines according to the protocol; Hemoglobin of ≥10 g/dl.

Exclusion: Prior treatment with aficamten or mavacamten; History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening; Current treatment with: moderate CYP2C9 inhibitors that are also moderate-to-strong CYP2D6 or CYP3A inhibitors (e.g., adagrasib, or more than a single dose of fluconazole); or strong CYP3A4 inducers that are also moderate CYP2C9 inducers (e.g., rifampicin or St. John's wort); Previous septal reduction therapy or has plans for either treatment during the trial period; Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM; Unrevascularized coronary artery stenosis of ≥ 70% or documented history of Type 1 myocardial infarction; Known allergies to therapeutic radiopharmaceuticals; History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, allergy or hypersensitivity to aficamten or excipients of placebo, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the trial evaluation, procedures, or completion; Significant valvular heart disease (per investigator judgment); Impaired renal function defined as eGFR under 25/ml/min.1.73cm2; Any (other) condition, disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may affect the interpretation of the results, or which might contribute substantially to the patient's experience of study burden (such as non-suppressible claustrophobia); History of LV systolic dysfunction (LVEF <45%); Pregnancy or breastfeeding; Paroxysmal or permanent atrial fibrillation - case to case revision per discretion of the PI; Inability to tolerate PET-CT (such as inability to lay still, claustrophobia).

EU CTIS 2025-523090-42-00