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

Recruitment Status
COMPLETED
(See Contacts and Locations)Verified March 2025 by Cytokinetics
Sponsor
Cytokinetics
Information Provided by (Responsible Party)
Cytokinetics
Clinicaltrials.gov Identifier
NCT05767346
Other Study ID Numbers:
CY 6032
First Submitted
March 1, 2023
First Posted
March 13, 2023
Last Update Posted
May 1, 2025
Last Verified
March 2025

ClinicalTrials.gov processed this data on April 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Obstructive Hypertrophic Cardiomyopathy (oHCM)
Drug: Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg)Drug: Placebo to match aficamten

Study Design

Study TypeInterventional
Actual Enrollment175 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleA 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
Study Start DateJune 19, 2023
Actual Primary Completion DateFebruary 27, 2025
Actual Study Completion DateMarch 27, 2025

Groups and Cohorts

Group/CohortIntervention/Treatment
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
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

Outcome Measures

Primary Outcome Measures
  1. Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
    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
    Effect of aficamten compared with metoprolol succinate on NYHA Functional Classification
  2. Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)
    Effect of aficamten compared with metoprolol succinate on participant health status
  3. Change in left ventricular mass index (LVMI)
    Effect of aficamten on mass of the heart as compared with metoprolol succinate
  4. Change in left atrial volume index (LAVI)
    Effect of aficamten on size of the heart as compared with metoprolol succinate
  5. Change from baseline values in NT-proBNP
    Effect of aficamten on NT-proBNP as compared with metoprolol succinate
  6. Change in post-Valsalva LVOT-G
    Effect of aficamten on post-Valsalva LVOT-G as compared with metoprolol succinate

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsCytokinetics
Locations
Alaska Heart and Vascular Institute | Anchorage Alaska, United States, 99508Mayo Clinic | Phoenix Arizona, United States, 85054UC San Diego Health - Sulpizio Cardiovascular Center | La Jolla California, United States, 92037Cedars-Sinai Medical Center (Smidt Heart Institute) | Los Angeles California, United States, 90048Yale New Haven Hospital | New Haven Connecticut, United States, 06519AdventHealth | Orlando Florida, United States, 32804Emory Clinic | Atlanta Georgia, United States, 30322Piedmont Fayette Hospital | Fayetteville Georgia, United States, 30214Northwestern University | Evanston Illinois, United States, 60208Massachusetts General Hospital | Boston Massachusetts, United States, 02114Brigham and Women's Hospital | Boston Massachusetts, United States, 02115Lahey Hospital & Medical Center | Burlington Massachusetts, United States, 01803Henry Ford Hospital | Detroit Michigan, United States, 48202Saint Luke's Hospital of Kansas City | Kansas City Missouri, United States, 64111Morristown Medical Center | Morristown New Jersey, United States, 07960Columbia University Medical Center/New York Presbyterian Hospital | New York New York, United States, 10032Sanger Heart & Vascular Institute - HCM Clinic | Charlotte North Carolina, United States, 28204Duke Health Center Arringdon | Morrisville North Carolina, United States, 27560Providence St. Vincent Medical Center | Portland Oregon, United States, 97225Oregon Health & Science University | Portland Oregon, United States, 97239Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania) | Philadelphia Pennsylvania, United States, 19104Medical University of South Carolina | Charleston South Carolina, United States, 29425Ascension Saint Thomas Heart West | Nashville Tennessee, United States, 37205Vanderbilt University Medical Center | Nashville Tennessee, United States, 37232CHI St. Luke's Health Baylor-St. Luke's Medical Center | Houston Texas, United States, 77030Houston Methodist Hospital | Houston Texas, United States, 77030Intermountain Medical Center | Murray Utah, United States, 84107Inova Schar Heart and Vascular | Falls Church Virginia, United States, 22042Institutdo Danta Pazzanese | Ibirapuera Ibirapuera, Brazil, 04012-909Instituto de Pesquisa Clinica de Campinas - IPECC | Campinas São Paulo, Brazil, 13060-080lnstituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo | São Paulo São Paulo, Brazil, 05403-900Institut universitaire de cardiologie et de pneumonlogie de Quebec - Universite Laval | Québec , Canada, Xiangya Second Hospital of Central South University | Changsha , China, The First Affiliated Hospital, Sun Yat-sen University | Guangzhou , China, 510080Guangdong Provincial People's Hospital | Guangzhou , China, Zhongshan Hospital Fudan University | Shanghai , China, Renmin Hospital of Wuhan University | Wuhan , China, The First Affiliated Hospital of Zhengzhou University | Zhengzhou , China, Aarhus University Hospital | Aarhus , Denmark, Copenhagen University Hospital | Copenhagen , Denmark, CHU La Timone | Marseille , France, Hopital Europeen Georges Pompidou | Paris , France, Hopital Lariboisiere - APHP | Paris , France, Hopital Cardiologique Haut Leveque - CHU de Bordeaux | Pessac , France, CHU Pontchaillou | Rennes , France, Hopital Laennec - CHU de Nantes | Saint-Herblain , France, Charite-Universitatsmedizin Berlin - Campus Virchow Klinikum | Berlin , Germany, Universitaetsklinikum Essen | Essen , Germany, Universitaetsklinikum Jena | Jena , Germany, Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika | Budapest , Hungary, Barzilai Medical Center | Ashkelon , Israel, Hadassah Hebrew Medical Center- Ein Kerem | Jerusalem , Israel, The Chaim Sheba Medical Center | Ramat Gan , Israel, Kaplan Medical Center | Rehovot , Israel, Ziv Medical Center | Safed , Israel, AOU Careggi | Florence , Italy, Erasmus Medical Center | Rotterdam , Netherlands, Complejo Hospitalario Universitario A Coruna | A Coruña , Spain, Hospital Clinic de Barcelona | Barcelona , Spain, Hospital Clinico Universitario Virgen Arrixaca | El Palmar , Spain, Hospital Universitario Puerta de Hierro | Madrid , Spain, Hospital Universitario de Salamanca | Salamanca , Spain, Hospital Universitario Virgen del Rocio | Seville , Spain, Hospital Universitario Virgen Macarena | Seville , Spain, Hospital Universitario Son Llatzer | Son Ferriol , Spain, NHS Greater Glasgow and Clyde | Glasgow , United Kingdom, Liverpool Heart and Chest Hospital NHS Foundation Trust | Liverpool , United Kingdom, Barts Health NHS Trust | London , United Kingdom, Royal Brompton Hospital | London , United Kingdom, St George's University Hospitals NHS Foundation Trust | London , United Kingdom, Oxford University Hospital NHS Trust - John Radcliffe Hospital - OCMR | Oxford , United Kingdom,
Investigators
Study Director: Scientific Leadership, Cytokinetics