Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM (MAPLE-HCM)

Cytokinetics

Status and phase: Enrolling; Phase 3

Conditions: Obstructive Hypertrophic Cardiomyopathy (oHCM)

Treatments: Drug: Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg); Drug: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg); Drug: Placebo to match aficamten; Drug: Placebo to match metoprolol succinate

Study type: Interventional

Funder types: Industry

Identifiers

NCT05767346

CY 6032

2023-504809-37-00 (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 170 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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170 participants in 2 patient groups

Aficamten up to 20 mg plus placebo for metoprolol

Experimental group

Description:

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.

Treatment:

Drug: Placebo to match metoprolol succinate

Drug: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg)

Metoprolol succinate up to 200 mg plus placebo for aficamten

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to match aficamten

Drug: Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg)