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

May 10, 2024 updated by: Cytokinetics

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
      • Québec, Canada
        • Recruiting
        • Institut universitaire de cardiologie et de pneumonlogie de Quebec - Universite Laval
  • China
      • Changsha, China
        • Recruiting
        • Xiangya Second Hospital of Central South University
      • Shanghai, China
        • Recruiting
        • Zhongshan Hospital Fudan University
      • Wuhan, China
        • Recruiting
        • Renmin Hospital of Wuhan University
      • Zhengzhou, China
        • Recruiting
        • The First Affiliated Hospital of Zhengzhou University
  • Denmark
      • Aarhus, Denmark
        • Recruiting
        • Aarhus University Hospital
      • Copenhagen, Denmark
        • Recruiting
        • Copenhagen University Hospital
  • France
      • Marseille, France
        • Recruiting
        • CHU La Timone
      • Paris, France
        • Recruiting
        • Hôpital Européen Georges Pompidou
      • Paris, France
        • Recruiting
        • Hopital Lariboisiere - APHP
      • Pessac, France
        • Recruiting
        • Hopital Cardiologique Haut Leveque - CHU de Bordeaux
      • Rennes, France
        • Recruiting
        • CHU Pontchaillou
      • Saint-Herblain, France
        • Recruiting
        • Hopital Laennec - CHU de Nantes
  • Germany
      • Berlin, Germany
        • Recruiting
        • Charite-Universitatsmedizin Berlin - Campus Virchow Klinikum
      • Jena, Germany
        • Recruiting
        • Universitaetsklinikum Jena
  • Hungary
      • Budapest, Hungary
        • Recruiting
        • Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika
  • Israel
      • Ashkelon, Israel
        • Recruiting
        • Barzilai Medical Center
      • Jerusalem, Israel
        • Recruiting
        • Hadassah Hebrew Medical Center- Ein Kerem
      • Ramat Gan, Israel
        • Recruiting
        • The Chaim Sheba Medical Center
      • Reẖovot, Israel
        • Recruiting
        • Kaplan Medical Center
      • Safed, Israel
        • Recruiting
        • Ziv Medical Center
  • Italy
      • Florence, Italy
        • Recruiting
        • AOU Careggi
  • Netherlands
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus Medical Center
  • Spain
      • A Coruña, Spain
        • Recruiting
        • Complejo Hospitalario Universitario A Coruna
      • Barcelona, Spain
        • Recruiting
        • Hospital Clinic de Barcelona
      • El Palmar, Spain
        • Recruiting
        • Hospital Clinico Universitario Virgen Arrixaca
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Puerta de Hierro
      • Salamanca, Spain
        • Recruiting
        • Hospital Universitario de Salamanca
      • Sevilla, Spain
        • Recruiting
        • Hospital Universitario Virgen del Rocio
      • Sevilla, Spain
        • Recruiting
        • Hospital Universitario Virgen Macarena
      • Son Ferriol, Spain
        • Recruiting
        • Hospital Universitario Son Llatzer
  • United Kingdom
      • Glasgow, United Kingdom
        • Recruiting
        • NHS Greater Glasgow and Clyde
      • Liverpool, United Kingdom
        • Recruiting
        • Liverpool Heart and Chest Hospital NHS Foundation Trust
      • London, United Kingdom
        • Recruiting
        • Royal Brompton Hospital
      • London, United Kingdom
        • Recruiting
        • Barts Health NHS Trust
      • Oxford, United Kingdom
        • Recruiting
        • Oxford University Hospital NHS Trust - John Radcliffe Hospital - OCMR
  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Recruiting
        • Alaska Heart and Vascular Institute
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • UC San Diego Health - Sulpizio Cardiovascular Center
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center (Smidt Heart Institute)
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • Yale New Haven Hospital
    • Florida
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory Clinic
      • Fayetteville, Georgia, United States, 30214
        • Recruiting
        • Piedmont Fayette Hospital
    • Illinois
      • Evanston, Illinois, United States, 60208
        • Recruiting
        • Northwestern University
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
      • Burlington, Massachusetts, United States, 01803
        • Recruiting
        • Lahey Hospital & Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • Saint Luke's Hospital of Kansas City
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Recruiting
        • Morristown Medical Center
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center/New York Presbyterian Hospital
    • North Carolina
      • Morrisville, North Carolina, United States, 27560
        • Recruiting
        • Duke Health Center Arringdon
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence St. Vincent Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37205
        • Recruiting
        • Ascension Saint Thomas Heart West
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • Recruiting
        • CHI St. Luke's Health Baylor-St. Luke's Medical Center
    • Utah
      • Murray, Utah, United States, 84107
        • Recruiting
        • Intermountain Medical Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Recruiting
        • Inova Schar Heart and Vascular

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline to Week 24
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
Baseline to Week 24
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
Baseline to Week 24
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
Baseline to Week 24
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
Baseline to Week 24
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
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cytokinetics

Investigators

  • Study Director: Scientific Leadership, Cytokinetics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 19, 2023

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

March 2, 2023

First Submitted That Met QC Criteria

March 2, 2023

First Posted (Actual)

March 14, 2023

Study Record Updates

Last Update Posted (Actual)

May 13, 2024

Last Update Submitted That Met QC Criteria

May 10, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CY 6032
  • 2023-504809-37-00 (Other Identifier: EU CTR Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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