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

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified January 2025 by Cytokinetics
Sponsor
Cytokinetics
Information Provided by (Responsible Party)
Cytokinetics
Clinicaltrials.gov Identifier
NCT05186818
Other Study ID Numbers:
CY 6031
First Submitted
December 22, 2021
First Posted
January 10, 2022
Results First Posted
January 14, 2026
Last Update Posted
March 2, 2026
Last Verified
January 2025

ClinicalTrials.gov processed this data on February 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

CY 6031 was a Phase 3, randomized, placebo-controlled, double-blind, multi-center trial in participants with symptomatic oHCM. Eligible participants were randomized in a 1:1 ratio to receive aficamten or placebo. Randomization was stratified by use of beta-blockers (yes or no) and cardiopulmonary exercise testing (CPET) exercise modality (treadmill or bicycle). Enrollment limits were applied as follows: participants taking beta-blockers were capped at approximately 70% of total enrollment; participants taking disopyramide were capped at approximately 10% of total enrollment; participants with persistent atrial fibrillation (AF) at screening were capped at approximately 15% of total enrollment; and participants using the bicycle CPET exercise modality were capped at approximately 50% of total enrollment.

Investigational product (IP) was administered orally once daily (QD) with or without food for 24 weeks. During the initial 6 weeks of the treatment period, IP doses were individually titrated at Weeks 2, 4, and 6 based on echocardiography-guided criteria. Dose escalation at Weeks 2, 4, and 6 occurred only if a participant had a Valsalva left ventricular outflow tract gradient (LVOT-G) ≥ 30 mmHg and a biplane left ventricular ejection fraction (LVEF) ≥ 55%. Echocardiograms were performed at each subsequent visit during the trial, and the IP dose was down-titrated if the LVEF was \< 50%. The primary endpoint of peak oxygen uptake (pVO2) was measured by CPET at screening and at the end of treatment (Week 24). A participant's background HCM therapy was individually optimized according to local practice prior to enrollment in the study.

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

Study Design

Study TypeInterventional
Actual Enrollment282 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
Study Start DateJanuary 31, 2022
Actual Primary Completion DateNovember 9, 2023
Actual Study Completion DateDecember 17, 2023

Groups and Cohorts

Group/CohortIntervention/Treatment
Aficamten up to 20 mg
Participants received 5 mg, 10 mg, 15 mg, or 20 mg of aficamten; dose levels were guided by echocardiography assessments. Treatment was administered for up to 24 weeks.
Drug: Aficamten (5 mg, 10 mg, 15 mg, and 20 mg)
Aficamten tablets were administered orally once daily.
Placebo to match aficamten
Participants received placebo for up to 24 weeks.
Drug: Placebo to match aficamten
Placebo tablets were administered orally once daily.

Outcome Measures

Primary Outcome Measures
  1. Change From Baseline in pVO2 at Week 24
    The effect of CK-3773274 on exercise capacity in participants with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) was determined through changes in peak oxygen uptake (pVO2) after 24 weeks of treatment. pVO2 was measured by cardiopulmonary exercise testing (CPET) on a treadmill or bicycle. A higher pVO2 indicates better cardiorespiratory fitness.
Secondary Outcome Measures
  1. Change From Baseline in KCCQ-CSS at Week 24
    The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.
  2. Change From Baseline in KCCQ-CSS at Week 12
    The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.
  3. Proportion of Participants With ≥1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 24
    The effect of aficamten on NYHA functional classification was evaluated through changes observed from baseline through 24 weeks of treatment.
  4. Proportion of Participants With ≥1 Class Improvement in NYHA Functional Class From Baseline to Week 12
    The effect of aficamten on NYHA functional classification was evaluated through changes observed from baseline through 12 weeks of treatment.
  5. Change From Baseline in Valsalva Left Ventricular Outflow Tract Gradient (LVOT-G) at Week 24
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.
  6. Change From Baseline in Valsalva LVOT-G at Week 12
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.
  7. Proportion of Participants With Valsalva LVOT G <30 mmHg at Week 24
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.
  8. Proportion of Participants With Valsalva LVOT G <30 mmHg at Week 12
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.
  9. Duration of SRT Eligibility During the 24-week Treatment Period for Participants Who Were SRT Eligible at Baseline
    The effect of aficamten treatment on the duration of septal reduction therapy (SRT) eligibility was evaluated over the 24- week treatment period.
  10. Change From Baseline to Week 24 in Total Workload During CPET
    Effect of aficamten on intensity of exercise (based on speed, incline, participant weight, etc.) during CPET. Workload is an indication of the energy expended during the exercise test.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Males and females between 18 and 85 years of age, inclusive, at screening.
Body mass index \<35 kg/m2.
Diagnosed with HCM per the following criteria:
Has LV hypertrophy and 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 of:
≥15 mm in one or more myocardial segments OR
≥13 mm in one or more wall segments and a known-disease-causing gene mutation or positive family history of HCM
Has resting LVOT-G ≥30 mmHg and post-Valsalva LVOT G ≥50 mmHg during screening as determined by the echocardiography core laboratory.
LVEF ≥60% at screening as determined by the echocardiography core laboratory.
New York Heart Association (NYHA) Functional Class II or III at screening.
Hemoglobin ≥10g/dL at screening.
Respiratory exchange ratio (RER) ≥1.05 and pVO2 ≤90% predicted on the screening CPET per the core laboratory.
Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for \>6 weeks prior to randomization and anticipate remaining on the same medication regimen during the trial. Patients treated with disopyramide must also be concomitantly treated with a beta blocker and/or calcium channel blocker. Key
Exclusion Criteria
Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).
Significant valvular heart disease (per investigator judgment).
Moderate-severe valvular aortic stenosis.
Moderate-severe mitral regurgitation not due to systolic anterior motion of the mitral valve.
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).
Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the trial period.
Documented paroxysmal atrial fibrillation during the screening period.
Paroxysmal or permanent atrial fibrillation is only excluded IF:
rhythm restoring treatment (eg, direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤6 months prior to screening.
rate control and anticoagulation have not been achieved for at least 6 months prior to screening.
History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
Has received prior treatment with CK-3773274 or mavacamten.

Contacts and Locations

Sponsors and CollaboratorsCytokinetics
Locations
Alaska Heart and Vascular Institute | Anchorage Alaska, United States, 99508UC San Diego Health - Sulpizio Cardiovascular Center | La Jolla California, United States, 92037Cedars-Sinai Medical Center - Smidt Heart Institute Clinic | Los Angeles California, United States, 90048University of California San Francisco | San Francisco California, United States, 94143Stanford University Hospital | Stanford California, United States, 94305Yale School of Medicine | New Haven Connecticut, United States, 06511Yale University School of Medicine | New Haven Connecticut, United States, 06519MedStar Washington Hospital Center | Washington D.C. District of Columbia, United States, 20010Holy Cross Hospital / Cardiology Associates | Fort Lauderdale Florida, United States, 33308Mayo Clinic Florida | Jacksonville Florida, United States, 32224Emory Clinic | Atlanta Georgia, United States, 30322Piedmont Fayette Hospital | Fayetteville Georgia, United States, 30214Northwestern University | Chicago Illinois, United States, 60614University of Iowa | Iowa City Iowa, United States, 52242MedStar Medical Group Cardiology at Union Memorial | Baltimore Maryland, United States, 21218Medstar Franklin Square Medical Center | Baltimore Maryland, United States, 21237Massachusetts General Hospital | Boston Massachusetts, United States, 02114Brigham and Women's Hospital | Boston Massachusetts, United States, 02115Lahey Hospital & Medical Center | Burlington Massachusetts, United States, 01805Michigan Medicine | Ann Arbor Michigan, United States, 48109Henry Ford Medical Center | Detroit Michigan, United States, 48202Spectrum Health Medical Group Cardiovascular Medicine | Grand Rapids Michigan, United States, 49525M Health Fairview University of Minnesota Medical Center - East Bank | Minneapolis Minnesota, United States, 55455Mayo Clinic | Rochester Minnesota, United States, 55905Saint Luke's Hospital of Kansas City | Kansas City Missouri, United States, 64111Washington University School of Medicine | St Louis Missouri, United States, 63110Morristown Medical Center | Morristown New Jersey, United States, 07960NYU Langone Health | New York New York, United States, 10016Mount Sinai Hospital | New York New York, United States, 10029Columbia University Medical Center/NY Presbyterian Hospital | New York New York, United States, 10032Westchester Medical Center | Valhalla New York, United States, 10595Sanger Heart and Vascular Institute | Charlotte North Carolina, United States, 10595Sanger Heart and Vascular Institute - HCM Clinic | Charlotte North Carolina, United States, 28204Duke Health Center Arringdon | Morrisville North Carolina, United States, 27560Cleveland Clinic | Cleveland Ohio, United States, 44195The Ohio State University Wexner Medical Center | Columbus Ohio, United States, 43210Ascension St. John Clinical Research Institute | Tulsa Oklahoma, United States, 74104Oregon Health & Science University | Portland Oregon, United States, 97239Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine) | Philadelphia Pennsylvania, United States, 19104UPMC Presbyterian | Pittsburgh Pennsylvania, United States, 15213Stern Cardiovascular Foundation, Inc | Germantown Tennessee, United States, 38138Vanderbilt University Medical Center | Nashville Tennessee, United States, 37232The University of Texas Southwestern Medical Center | Dallas Texas, United States, 75390Houston Methodist Hospital | Houston Texas, United States, 77030University of Utah Hospital | Salt Lake City Utah, United States, 84132University of Virginia Health System University Hospital | Charlottesville Virginia, United States, 22908University of Washington Medical | Seattle Washington, United States, 98195Froedtert Hospital | Milwaukee Wisconsin, United States, 53226Beijing Chao-Yang Hospital, Capital Medical University | Beijing Beijing Municipality, China, 100020Beijing Anzhen Hospital | Beijing Beijing Municipality, China, 100029Peking University Third Hospital | Beijing Beijing Municipality, China, 10019Nanfang Hospital Southern Medical University | Guanzhou Guangdong, China, 516006The First Affiliated Hospital of Zhengzhou University | Zhengzhou Henan, China, 450018Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology | Wuhan Hubei, China, 430022Xiangya Hospital of the Central South University | Changsha Hunan, China, 410008The First Hospital of Jinlin University | Changchun Jinlin, China, 130031The First Affiliated Hospital of Xi'an Jiaotong University | Xi’an Shanxi, China, 710061Charles University | Prague , Czechia, 128 08Interni klinika kardiologie a angiologie | Prague , Czechia, 12808Aalborg University Hospital, Department of Cardiology | Aalborg , Denmark, 9100Department of Cardiology Aarhus University Hospital | Aarhus , Denmark, 8200Hjertecentret (The Heart Center) | Copenhagen , Denmark, 2100Copenhagen University Hospital | Copenhagen , Denmark, 2400Hopital Universitaire de Rangueil (CHU de Toulouse) Service de Cardiologie | Toulouse Cedex, France, 31059CHU de Marseille - Hopital de la Timone Service de cardiologie | Marseille , France, 13005CHU de Nantes | Nantes , France, 44093Hopital Lariboisiere, Service de Cardiologie | Paris , France, 75010Hôpital Européen Georges Pompidou | Paris , France, 75015CHU Pitie-Salpetriere, Centre de reference maladies cardiaques hereditaires ou rares | Paris , France, CHU de Bordeaux Hopital Cardiologique Haut-Leveque | Pessac , France, 33600CHU du Haut Lveque Cardiologie | Pessac , France, 33604Kerckhoff-Klinik GmbH Abteilung Administration Forschung und Lehre | Bad Nauheim , Germany, 61231Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum (CVK) Medizinische Klinik mit Schwerpunkt Kardiologie | Berlin , Germany, 13353Universitaetsklinikum Essen Westdeutsches Herz-Gefaesszentrum | Essen , Germany, 45147Klinikumder Georg-August-Universitaet | Göttingen , Germany, 37075Universitaetsmedizin Goettingen | Göttingen , Germany, 37075Universitaetsklinikum Heidelberg | Heidelberg , Germany, Universitaetsklinikum Jena Klinik fuer Innere Medizin 1 | Jena , Germany, 07747Unniversitaetsklinikum Magdeburg Klinik fur Kardiologie und Anglologie | Magdeburg , Germany, 39120Universitätsklinikum Würzburg | Würzburg , Germany, Semmelweis Egyetem Varosmajori Sziv es Ergyogyasazati Klinika | Budapest , Hungary, The Olga & Lev Leviev Heart Center The Chaim Sheba Medical Center | Ramat Gan Tel Hasomer, Israel, 5265601The Barzilai University Medical Center | Ashkelon , Israel, 78100The Barzilai University Medical Center | Ashkelon , Israel, 7830604Hadassah Medical Center- Ein Kerem | Jerusalem , Israel, 9112001Kaplan Medical Center | Rehovot , Israel, 76100Ziv Medical Center | Safed , Israel, 13100UOC Cardiologica Azienda Ospedaliera Spedali Civili di Brescia | Brescia , Italy, 25123Azienda Ospedaliero Universitaria Careggi Dipartimento Cardiotoracovascolare - Cardiomiopatie Unit | Florence , Italy, 50134Fondazione toscana Gabriele Monesterio per la ricarca medica Dipartimento Cardiotoracico UOC Cardiologia e Medicina Cardiovasculare Ospedale San Cataldo | Pisa , Italy, 56124Dipartimento di Medicina Clinica e Molecolare Universita Sapienza di Roma Unita di Terapia Intensiva Cardiologica Azienda Ospedaliero Universitaria Sant'Andrea | Roma , Italy, 1035-39Amsterdam UMC, location AMC | Amsterdam , Netherlands, 1105University Hospital Maastricht | Maastricht , Netherlands, 6229HXErasmus Medical Center | Rotterdam , Netherlands, 3015Narodowy Instytut Kardiologii Stefana Kardynała Wyszynskiego- Panstwowy Instytut Badawczy | Warsaw Masovian Voivodeship, Poland, 04-628Kardio Brynow S.C | Katowice , Poland, Krakowskie Centrum | Krakow , Poland, Centro Hospitalar Do Baixo Vouga, EPE AV ARTUR RAVARA | Aveiro , Portugal, 3814-501Hospital da Luz | Lisbon , Portugal, 1500-650Complejo Hospitalario Universitario | A Coruña La Coruna, Spain, 15006Hospital Universitario Puerta de Hierro | Madrid Majadahonda, Spain, Hospital Clinic de Barcelona | Barcelona , Spain, 08036Hospital Clinico Universitario Virgen de la Arrixaca | Murcia , Spain, Hospital Universitario Son Llatzer Secretaria de Cardiologia | Palma , Spain, 07198Hospital Universitario de Salamanca | Salamanca , Spain, 37007Hospital Universitario Virgen Macarena-merge | Seville , Spain, 41009Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust | Edgbaston Birmingham, United Kingdom, B15 2GWQueen Elizabeth University Hospital - HWS Greater Glasgow and Clyde | Glasgow , United Kingdom, G1 4TFLiverpool Heart and Chest Hospital - Liverpool Heart and Chest Hospital NHS Foundation Trust- HWS Greater Glasgow and Clyde | Liverpool , United Kingdom, L14 3LBBarts Health NS Trust | London , United Kingdom, EC1A 7BESt George's University Hospitals NHS Foundation Trust | London , United Kingdom, SW17 0QTRoyal Brompton Hospital | London , United Kingdom, SW3 6NPOxford Centre for Clinical Magnetic Resonance Research | Oxford , United Kingdom, OX3 9DURadcliffe Department of Medicine | Oxford , United Kingdom, OX3 9DU
Investigators
Study Director: Cytokinetics MD, Cytokinetics
Study Documents (Full Text)
Documents provided by Cytokinetics: Study Protocol  December 7, 2023Documents provided by Cytokinetics: Statistical Analysis Plan  October 1, 2023