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

NCT ID: NCT05767346

Last Updated: 2025-05-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-20

Study Completion Date

2025-03-28

Brief Summary

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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

Detailed Description

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Conditions

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Obstructive Hypertrophic Cardiomyopathy (oHCM)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

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

Intervention Type DRUG

Aficamten (CK-3773274) tablets administered orally

Placebo to match metoprolol succinate

Intervention Type DRUG

Placebo for metoprolol succinate administered orally

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.

Group Type ACTIVE_COMPARATOR

Placebo to match aficamten

Intervention Type DRUG

Placebo for aficamten (CK-3773274) administered orally

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

Intervention Type DRUG

Metoprolol succinate tablets administered orally

Interventions

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

Aficamten (CK-3773274) tablets administered orally

Intervention Type DRUG

Placebo to match aficamten

Placebo for aficamten (CK-3773274) administered orally

Intervention Type DRUG

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

Metoprolol succinate tablets administered orally

Intervention Type DRUG

Placebo to match metoprolol succinate

Placebo for metoprolol succinate administered orally

Intervention Type DRUG

Eligibility Criteria

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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 KCCQ-CSS score of ≤ 90 at screening
* 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
* Respiratory exchange ratio (RER) ≥ 1.05 and peak oxygen uptake (pVO2) \< 100% predicted on the screening CPET per the core laboratory
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Cytokinetics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scientific Leadership

Role: STUDY_DIRECTOR

Cytokinetics

Locations

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Alaska Heart and Vascular Institute

Anchorage, Alaska, United States

Site Status

Mayo Clinic

Phoenix, Arizona, United States

Site Status

UC San Diego Health - Sulpizio Cardiovascular Center

La Jolla, California, United States

Site Status

Cedars-Sinai Medical Center (Smidt Heart Institute)

Los Angeles, California, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

AdventHealth

Orlando, Florida, United States

Site Status

Emory Clinic

Atlanta, Georgia, United States

Site Status

Piedmont Fayette Hospital

Fayetteville, Georgia, United States

Site Status

Northwestern University

Evanston, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Columbia University Medical Center/New York Presbyterian Hospital

New York, New York, United States

Site Status

Sanger Heart & Vascular Institute - HCM Clinic

Charlotte, North Carolina, United States

Site Status

Duke Health Center Arringdon

Morrisville, North Carolina, United States

Site Status

Providence St. Vincent Medical Center

Portland, Oregon, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Ascension Saint Thomas Heart West

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

CHI St. Luke's Health Baylor-St. Luke's Medical Center

Houston, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Inova Schar Heart and Vascular

Falls Church, Virginia, United States

Site Status

Institutdo Danta Pazzanese

Ibirapuera, Ibirapuera, Brazil

Site Status

Instituto de Pesquisa Clinica de Campinas - IPECC

Campinas, São Paulo, Brazil

Site Status

lnstituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status

Institut universitaire de cardiologie et de pneumonlogie de Quebec - Universite Laval

Québec, , Canada

Site Status

Xiangya Second Hospital of Central South University

Changsha, , China

Site Status

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, , China

Site Status

Guangdong Provincial People's Hospital

Guangzhou, , China

Site Status

Zhongshan Hospital Fudan University

Shanghai, , China

Site Status

Renmin Hospital of Wuhan University

Wuhan, , China

Site Status

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Copenhagen University Hospital

Copenhagen, , Denmark

Site Status

CHU La Timone

Marseille, , France

Site Status

Hopital Europeen Georges Pompidou

Paris, , France

Site Status

Hopital Lariboisiere - APHP

Paris, , France

Site Status

Hopital Cardiologique Haut Leveque - CHU de Bordeaux

Pessac, , France

Site Status

CHU Pontchaillou

Rennes, , France

Site Status

Hopital Laennec - CHU de Nantes

Saint-Herblain, , France

Site Status

Charite-Universitatsmedizin Berlin - Campus Virchow Klinikum

Berlin, , Germany

Site Status

Universitaetsklinikum Essen

Essen, , Germany

Site Status

Universitaetsklinikum Jena

Jena, , Germany

Site Status

Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika

Budapest, , Hungary

Site Status

Barzilai Medical Center

Ashkelon, , Israel

Site Status

Hadassah Hebrew Medical Center- Ein Kerem

Jerusalem, , Israel

Site Status

The Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Ziv Medical Center

Safed, , Israel

Site Status

AOU Careggi

Florence, , Italy

Site Status

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

Complejo Hospitalario Universitario A Coruna

A Coruña, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital Clinico Universitario Virgen Arrixaca

El Palmar, , Spain

Site Status

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital Universitario Son Llatzer

Son Ferriol, , Spain

Site Status

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Barts Health NHS Trust

London, , United Kingdom

Site Status

Royal Brompton Hospital

London, , United Kingdom

Site Status

St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Oxford University Hospital NHS Trust - John Radcliffe Hospital - OCMR

Oxford, , United Kingdom

Site Status

Countries

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United States Brazil Canada China Denmark France Germany Hungary Israel Italy Netherlands Spain United Kingdom

References

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Hegde SM, Wang X, Garcia-Pavia P, Getchevski S, Masri A, Merkely B, Nassif ME, Pena-Pena ML, Barriales-Villa R, Bilen O, Burroughs M, Claggett B, Costabel JP, Correia EB, Dybro AM, Elliott P, Lakdawala NK, Mann A, Maron MS, Nair A, Poulsen SH, Reant P, Schulze PC, Wang A, Sohn R, Berhane I, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Wohltman A, Fifer MA, Solomon SD; MAPLE-HCM Investigators. Effect of Aficamten Compared With Metoprolol on Echocardiographic Measures in Symptomatic Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM. J Am Coll Cardiol. 2025 Aug 27:S0735-1097(25)07466-2. doi: 10.1016/j.jacc.2025.08.022. Online ahead of print.

Reference Type DERIVED
PMID: 40932433 (View on PubMed)

Garcia-Pavia P, Maron MS, Masri A, Merkely B, Nassif ME, Pena-Pena ML, Barriales-Villa R, Bilen O, Burroughs M, Claggett B, Costabel JP, Correia EB, Dybro AM, Elliott P, Hegde SM, Lakdawala NK, Lewis GD, Mann A, Miao ZM, Nair A, Poulsen SH, Reant P, Schulze PC, Solomon SD, Wang A, Sohn R, Berhane I, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Wohltman A, Fifer MA; MAPLE-HCM Investigators. Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2025 Sep 11;393(10):949-960. doi: 10.1056/NEJMoa2504654. Epub 2025 Aug 30.

Reference Type DERIVED
PMID: 40888697 (View on PubMed)

Garcia-Pavia P, Bilen O, Burroughs M, Costabel JP, de Barros Correia E, Dybro AM, Elliott P, Lakdawala NK, Mann A, Nair A, Nassif ME, Poulsen SH, Reant P, Schulze PC, Wang A, Berhane I, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Meng L, Sohn R, Wohltman A, Fifer MA; MAPLE-HCM Study Investigators. Aficamten vs Metoprolol for Obstructive Hypertrophic Cardiomyopathy: MAPLE-HCM Rationale, Study Design, and Baseline Characteristics. JACC Heart Fail. 2025 Feb;13(2):346-357. doi: 10.1016/j.jchf.2024.11.011.

Reference Type DERIVED
PMID: 39909646 (View on PubMed)

Other Identifiers

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2023-504809-37-00

Identifier Type: OTHER

Identifier Source: secondary_id

CY 6032

Identifier Type: -

Identifier Source: org_study_id

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