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

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ClinicalTrials.gov Identifier: NCT05767346
Recruitment Status : Recruiting
First Posted : March 14, 2023
Last Update Posted : May 20, 2024
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Brief Summary:
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 or disease Intervention/treatment Phase
Obstructive Hypertrophic Cardiomyopathy (oHCM) Drug: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg) Drug: Placebo to match aficamten Drug: Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg) Drug: Placebo to match metoprolol succinate Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 19, 2023
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : October 2025


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET) [ Time Frame: Baseline to Week 24 ]
    Effect of aficamten compared with metoprolol succinate on exercise capacity in patients with symptomatic oHCM


Secondary Outcome Measures :
  1. Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class [ Time Frame: Baseline to Week 24 ]
    Effect of aficamten compared with metoprolol succinate on NYHA Functional Classification

  2. Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [ Time Frame: Baseline to Week 24 ]
    Effect of aficamten compared with metoprolol succinate on patient health status

  3. Change in left ventricular mass index (LVMI) [ Time Frame: Baseline to Week 24 ]
    Effect of aficamten on mass of the heart as compared with metoprolol succinate

  4. Change in left atrial volume index (LAVI) [ Time Frame: Baseline to Week 24 ]
    Effect of aficamten on size of the heart as compared with metoprolol succinate

  5. Change from baseline values in NT-proBNP from baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
    Effect of CK-¬3773274 on NT-proBNP

  6. Change in post-Valsalva LVOT-G from baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
    Effect of aficamten on post-Valsalva LVOT-G



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05767346


Contacts
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Contact: Cytokinetics MD 650-624-2929 medicalaffairs@cytokinetics.com

Locations
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Sponsors and Collaborators
Cytokinetics
Investigators
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Study Director: Scientific Leadership Cytokinetics
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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT05767346    
Other Study ID Numbers: CY 6032
2023-504809-37-00 ( Other Identifier: EU CTR Number )
First Posted: March 14, 2023    Key Record Dates
Last Update Posted: May 20, 2024
Last Verified: December 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cytokinetics:
Obstructive Hypertrophic Cardiomyopathy
Aficamten
Metoprolol
oHCM
CK-3773274
CK-274
MAPLE-HCM
MAPLE
CY 6032
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Aortic Valve Disease
Heart Valve Diseases
Metoprolol
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action