Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM

Purpose

The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction

Condition

  • Obstructive Hypertrophic Cardiomyopathy (oHCM)

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Aficamten up to 20 mg plus placebo for metoprolol 		Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.
  • Drug: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg)
    Aficamten (CK-3773274) tablets administered orally
  • Drug: Placebo to match metoprolol succinate
    Placebo for metoprolol succinate administered orally
Active Comparator
Metoprolol succinate up to 200 mg plus placebo for aficamten 		Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.
  • Drug: Placebo to match aficamten
    Placebo for aficamten (CK-3773274) administered orally
  • Drug: Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg)
    Metoprolol succinate tablets administered orally

More Details

Status
Active, not recruiting
Sponsor
Cytokinetics

Study Contact