Mavacamten in symptomatic adolescent patients with obstructive hypertrophic cardiomyopathy: design of the phase 3 SCOUT-HCM trial.

Background: Mavacamten, a first-in-class cardiac myosin inhibitor, is approved internationally for the treatment of symptomatic adult patients with obstructive hypertrophic cardiomyopathy (HCM) and has been shown to improve cardiac function and symptoms in adult patients across multiple phase 3 trials. Efficacy and safety of mavacamten in pediatric patients with obstructive HCM has not been evaluated.

Methods: SCOUT-HCM is a phase 3, randomized, placebo-controlled, double-blind, parallel-group, multicenter, international study in symptomatic adolescent patients (12 years to < 18 years old) with obstructive HCM. The aim of the study is to assess the efficacy, safety, and pharmacokinetics of mavacamten in this population. Participants will be randomized 1:1 to mavacamten or placebo for 28 weeks, followed by a 28-week active-treatment period (when patients randomized to placebo will cross over to mavacamten) and an open-label long-term extension period for ≤ 144 weeks. Participants will initiate mavacamten at a dosage of 2.5 mg/day or 5 mg/day; dose titration will be based on echocardiographic assessment of Valsalva left ventricular (LV) outflow tract (LVOT) gradient and LV ejection fraction. The primary endpoint is change from baseline to week 28 in Valsalva LVOT gradient. Secondary endpoints include efficacy parameters of resting and post-exercise LVOT gradients, peak oxygen consumption, symptoms, and health status, plus safety and pharmacokinetic parameters.

Conclusions: SCOUT-HCM is the first clinical trial to evaluate a cardiac myosin inhibitor in adolescent patients with obstructive HCM. SCOUT-HCM will assess the utility of mavacamten in this patient population with an unmet clinical need. Trial registration ClinicalTrials.gov: NCT06253221.