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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified December 2025 by Cytokinetics
Sponsor
Cytokinetics
Information Provided by (Responsible Party)
Cytokinetics
Clinicaltrials.gov Identifier
NCT06081894
Other Study ID Numbers:
CY 6033
First Submitted
August 30, 2023
First Posted
October 12, 2023
Last Update Posted
February 1, 2026
Last Verified
December 2025

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

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
Drug: AficamtenDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment500 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase 3, Multi-Center, Randomized, Double-Blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
Study Start DateAugust 29, 2023
Actual Primary Completion Date1mo 1w from now
Actual Study Completion Date4mos 1w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Aficamten
Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose levels guided by echocardiography assessments, for up to 72 weeks.
Drug: Aficamten
Oral Tablet
Placebo
Participants in this arm will receive placebo, for up to 72 weeks.
Drug: Placebo
Oral Tablet

Outcome Measures

Primary Outcome Measures
  1. Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)
    Effect of aficamten compared with placebo on participant health status
  2. Change in pVO2
    Effect of aficamten compared with placebo on maximal exercise capacity
Secondary Outcome Measures
  1. Change in composite of two Z-scores of CPET parameters (pVO2 and VE/VCO2 slope)
    Effect of aficamten compared with placebo on global exercise capacity based on maximal and sub-maximal exercise performance
  2. Proportion of participants with ≥ 1 class improvement in NYHA Functional Class
    Effect of aficamten compared with placebo on NYHA Functional Classification
  3. Change in NT-proBNP
    Effect of aficamten compared with placebo on a biomarker of cardiac wall stress
  4. Change in LAVI in participants without atrial fibrillation or flutter at baseline on ECG
    Effect of aficamten compared with placebo on echocardiographic measures of structural remodeling
  5. Time to first CV event
    Effect of aficamten compared with placebo on cardiovascular events (ie, CV death, heart transplantation or left ventricular assist device, aborted sudden cardiac death, non-fatal stroke, heart failure hospitalization, or cardiac arrhythmia (atrial fibrillation or ventricular tachyarrhythmia) requiring treatment or hospitalization)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Between 18-85 years of age
Body mass index \< 40 kg/m2
Diagnosed with nHCM and has a screening echocardiogram with the following:
End-diastolic left ventricular (LV) wall thickness:
≥ 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 AND
Resting LVOT-G \< 30 mmHg AND Valsalva LVOT-G \< 50 mmHg AND
LVEF ≥ 60%
Participants with a history of intracavitary obstruction are eligible.
NYHA class II or III
Respiratory exchange ratio of ≥ 1.00 at screening by cardiopulmonary exercise testing (CPET) and predicted peak oxygen uptake (pVO2) ≤ 90% for age and sex
KCCQ-CSS score of ≤ 85
NT-proBNP of:
NT-pro BNP ≥ 300 pg/mL or NT-proBNP ≥ 900 pg/mL if in atrial fibrillation or atrial flutter OR
For Black participants, an NT-pro BNP ≥ 225 pg/mL or NT-proBNP ≥ 675 pg/mL if in atrial fibrillation or atrial flutter
Exclusion Criteria
Significant valvular heart disease (per Investigator judgment)
Moderate or severe valvular aortic stenosis or fixed subaortic obstruction
Moderate or severe mitral regurgitation
Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
Known current unrevascularized coronary artery stenosis of ≥ 70% or documented history of myocardial infarction.
History of LV systolic dysfunction (LVEF \< 45%) or stress cardiomyopathy
Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
Documented room air oxygen saturation reading \< 90% at screening or history of significant chronic obstructive pulmonary disease or severe/significant pulmonary hypertension
History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 3 months prior to screening
History of resistant hypertension (persistently elevated blood pressure despite maximal doses of 3 or more classes of medications for hypertension control)
Screening diastolic blood pressure ≥ 100 mmHg
Received prior treatment with aficamten
Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening)
Undergone septal reduction therapy \< 6 months prior to screening
Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period
Paroxysmal or permanent atrial fibrillation is excluded only if:
rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 3 months prior to screening
rate control and anticoagulation have not been achieved for at least 3 months prior to screening.

Contacts and Locations

Sponsors and CollaboratorsCytokinetics
Locations
University of Alabama at Birmingham | Birmingham Alabama, United States, 35233UC San Diego Health - Sulpizio Cardiovascular Center | La Jolla California, United States, 92037Keck Medical Center of USC (Outpatient Clinic) | Los Angeles California, United States, 90033Cedars-Sinai Medical Center (Smidt Heart Institute) | Los Angeles California, United States, 90048UCLA Medical Center Cardiovascular Clinic | Los Angeles California, United States, 90095University of California San Francisco | San Francisco California, United States, 94143Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center | Torrance California, United States, 90502Yale New Haven Hospital | New Haven Connecticut, United States, 06519MedStar Washington Hospital Center | Washington D.C. District of Columbia, United States, 20010Holy Cross Medical Group - Cardiology Associates | Fort Lauderdale Florida, United States, 33308Investigational Drug Services, AdventHealth Orlando | Orlando Florida, United States, 32804Emory Clinic | Atlanta Georgia, United States, 30322Piedmont Heart Institute (CPET) | Fayetteville Georgia, United States, 30214The Queen's Medical Center-Punchbowl | Honolulu Hawaii, United States, 96813Northwestern University | Evanston Illinois, United States, 60208Ascension St. Vincent | Indianapolis Indiana, United States, 46260University of Iowa Hospitals and Clinics | Iowa City Iowa, United States, 52242The University of Kansas Medical Center | Kansas City Kansas, United States, 66160MedStar Union Memorial Hospital | Baltimore Maryland, United States, 21218Massachusetts General Hospital | Boston Massachusetts, United States, 02114Brigham and Women's Hospital | Boston Massachusetts, United States, 02115Lahey Hospital & Medical Center | Burlington Massachusetts, United States, 01803Michigan Medicine | Ann Arbor Michigan, United States, 48109Henry Ford Hospital | Detroit Michigan, United States, 48202M 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, 64111Morristown Medical Center | Morristown New Jersey, United States, 07960Northwell Health North Shore University Hospital | Manhasset New York, United States, 11030NYU Langone Health | New York New York, United States, 10016Weill Cornell Medicine | New York New York, United States, 10021Mount Sinai Hospital | New York New York, United States, 10029Columbia University Medical Center/New York Presbyterian Hospital | New York New York, United States, 10032Westchester Medical Center | Valhalla New York, United States, 10595Sanger Heart & Vascular Institute - HCM Clinic | Charlotte North Carolina, United States, 28204The Lindner Research Center at The Christ Hospital | Cincinnati Ohio, United States, 45219University Hospitals Cleveland Medical Center | Cleveland Ohio, United States, 44106Cleveland Clinic | Cleveland Ohio, United States, 44195Providence St. Vincent Medical Center | Portland Oregon, United States, 97225Oregon Health & Science University | Portland Oregon, United States, 97239Hospital of the University of Pennsylvania | Philadelphia Pennsylvania, United States, 19104UPMC Presbyterian | Pittsburgh Pennsylvania, United States, 15213Medical University of South Carolina | Charleston South Carolina, United States, 29425Greenville Memorial Hospital | Greenville South Carolina, United States, 29605-5601Ascension Saint Thomas Heart West | Nashville Tennessee, United States, 37205Vanderbilt University Medical Center | Nashville Tennessee, United States, 37232Baylor College of Medicine | Houston Texas, United States, 77030Houston Methodist Hospital | Houston Texas, United States, 77030Intermountain Medical Center | Murray Utah, United States, 84107University of Utah Health | Salt Lake City Utah, United States, 84132University of Virginia | Charlottesville Virginia, United States, 22903Inova Health Care Services | Falls Church Virginia, United States, 22042VCU Health Downtown Medical Campus | Richmond Virginia, United States, 23298Carilion Clinic Cardiology | Roanoke Virginia, United States, 24014Virginia Mason Medical Center | Seattle Washington, United States, 98101Providence Sacred Heart Medical Center & Children's Hospital (CPET) | Spokane Washington, United States, 99204WVU Medicine | Morgantown West Virginia, United States, 26506University of Wisconsin Hospitals and Clinics | Madison Wisconsin, United States, 53792Aurora St. Luke's Medical Center | Milwaukee Wisconsin, United States, 53215Medical College of Wisconsin/Froedtert Hospital | Milwaukee Wisconsin, United States, 53226Hospital Italiano de Buenos Aires Juan Domingo Peron | Buenos Aires , Argentina, 119ICBA - Instituto Cardiovascular de Buenos Aires | Buenos Aires , Argentina, C1428Hospital Privado Centro Medico de Cordoba S.A | Córdoba , Argentina, X5016KEHThe Prince Charles Hospital | Chermside Queensland, Australia, 4032Flinders Medical Centre Cardiology Research | Adelaide South Australia, Australia, 5042Fiona Stanley Hospital, AHF Unit | Murdoch , Australia, 6150Instituto D'Or de Pesquisa e Ensino/Cardio Pulmonar da Bahia SA | Ondina Salvador, Brazil, 40170-0130Fundacao Felice Rocho / Hospital Felicio Rocho | Minas Gerais , Brazil, 30110-934NUPEC Cardio / Cardio HVC | Minas Gerais , Brazil, 30220-140CLINICOR Clinica Cardiologica LTDA | Ribeirão Preto , Brazil, 14026-900Instituto Dante Pazzanese de Cardiologia | São Paulo , Brazil, 04012-909Instituto do Coracao do Hospital de Aguiar | São Paulo , Brazil, 05403-900Associacao Lar Sao Francisco de Assis na Providencia de Deus - Hospital Universitario Sao Francisco na Providencia de Deus (HUSF) | São Paulo , Brazil, 12916-542Saraiva & Berlinger LTDA - EPP/IPECC - Instituto de Pesquisa Clinical de Campinas | São Paulo , Brazil, 13060-080Hospital das Clinicas de Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo - HCFMRP | São Paulo , Brazil, 14051-140Royal Alexandra Hospital | Edmonton Alberta, Canada, T5H 3V9St. Boniface Hospital | Winnipeg Manitoba, Canada, R2H 2A6Health Sciences North | Greater Sudbury Ontario, Canada, P3E 5J1Montreal Heart Institute | Montreal Quebec, Canada, H1T 1C8QEII Health Science Centre (Halifax Infirmary site) | Halifax , Canada, B3H 3A7The 1st Affiliated Hospital of Sun Yat-sen University | Guangzhou Guangdong, China, 510080Peking University First Hospital | Beijing , China, 100034Fuwai Hospital, CAMS & PUMC | Beijing , China, 100037Guangdong Provincial People's Hospital | Guangzhou , China, 519041The First Hospital of Jilin University | Jilin , China, 130031Zhongda Hospital Southeast University | Nanjin , China, 210009Shanghai Ruijin Hospital Luwan Branch | Shanghai , China, 200020Zhongshan Hospital Fudan University | Shanghai , China, 200032People's Hospital of Liaoning Province | Shenyang , China, 110067Remin Hospital of Wuhan University | Wuhan , China, 430060The 1st affi. Hospital of Xi'an Jiaotong University | Xi'an , China, 710061The 1st affiliated Hospital of Zhengzhou University | Zhenzhou , China, 450052Aarhus University Hospital | Aarhus , Denmark, 8200Department of Cardiology Copenhagen University Hospital, Bispebjerg | Copenhagen , Denmark, 2400Odense University Hospital, Department of Cardiology | Odense , Denmark, 5000Assistance Publique Hopitaux de Marseille | Marseille , France, 13005Clinique Du Millenaire | Montpellier , France, 34000Centre Hospitalier Universitaire De Montpellier | Montpellier , France, 34295Assistance Publique Hopitaux De Paris | Paris , France, 75010Assistance Publique Hopitaux de Paris | Paris , France, 75015Centre Hospitalier Universitaire De Bordeaux | Pessac , France, 33600Centre Hospitalier Universitaire De Nantes | Saint-Herblain , France, 44800Hopital Rangueil | Toulouse , France, 31059Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum (CVK) Medizinische Klinik mit Schwerpunkt Kardiologie | Berlin , Germany, 13353Herzzentrum der Universitatsmedizin Gottingen | Göttingen , Germany, 37075Universitaesklinkum Heidelberg Klinik fuer Kardiologie, Angeiologie und Pneumologie | Heidelberg , Germany, 69120Univeristy Hospital Jena Clinic for Internal Medicine I (Cardiology, Angiology, Internal Intensive Care Medicine) | Jena , Germany, 07747Evangelismos General Hospital of Athens | Athens , Greece, 10676"Hippokration" General Hospital of Athens | Athens , Greece, 11527University General Hospital Attikon | Attiki , Greece, 12462Onassis Cardiac Surgery Center | Kallithea , Greece, 17674Semmelweis Egyetem Varosmajori Sziv- es Ergyogyaszati Klinika | Budapest , Hungary, 1122University of Szeged | Szeged , Hungary, 6725Landspitali University Hospital | Reykjavik , Iceland, 101The Barzilai University Medical Center 2 - Cardiology Division | Ashkelon , Israel, 7830604Division of Cardiology Hadassah Medical Center | Jerusalem , Israel, 9112001Meir Medical Center | Kfar Saba , Israel, 4428164The Chaim Sheba Medical Center | Ramat Gan , Israel, 5265601Ziv Medical Center | Safed , Israel, 1311001Cardiology Department IRCCS San Donato Hospital - University of Milan | San Donato Milanese Milano, Italy, 20097UOC Cardiologica | Brescia , Italy, 25123Azienda Ospedaliera Universitaria Careggi pad. 13 Clinica Medica II Plano Cardiologia | Florence , Italy, 50134Cardiologia Universitaria - UTIC - Riabilitazione Cardiologica Azienda Ospedaliero Universitaria - Ospedali Riuniti | Foggia , Italy, 71122Unita Operativa di Riabilitazione Cardiologica, Istituto Auxologico Italiano, IRCCS - Auxologico San Luca, Piazzale Brescia, 20 | Milan , Italy, 20149Dipartimento Cardio-toraco- vascolare, ASST Grande Ospedale Metropolitano, NiguardaPiazza Ospedale Maggiore, 3 | Milan , Italy, 20162Dipartimento di Emergenze Cardiovascolari, Medicina Clinica e dell'Invecchiamento, AOU Federico II | Naples , Italy, 80131Fondazione Toscana Gabriele Monasterio Per La ricerca Medica e Di Sanita Pubbliga (FTGM) Cardio-Toracic-UOC Cardiology and Cardiovasulcar Medicine San Cataldo Hospital at CNR | Pisa , Italy, 56124Dipartimento Cardiopolmonare, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele | Roma , Italy, 00163Azienda Sanitaria Universitaria Giuliano Isontina Trieste SC Cardiologia | Trieste , Italy, 34148Kyushu University Hospital | Fukuoka , Japan, 812-8582Kobe City Medical Center General Hospital | Hyōgo , Japan, 650{047Hyogo Prefectural Harima-Himeii General Medical Center | Hyōgo , Japan, 670-8560University of Tsukuba Hospital | Ibaraki , Japan, 305-8576SHOWA Medical University Fujigaoka Hospital | Kanagawa , Japan, 227-8501Kochi Medical School Hospital | Kochi , Japan, 783-8505National Hospital Organization Kyoto Medical Center | Kyoto , Japan, 612-0861Mie University Hospital | Mie , Japan, 514-8507National University Corporation Tohoku University Tohoku University Hospital | Miyagi , Japan, 980-8574Shinshu University Hospital | Nagano , Japan, 390-8621Osaka Metropolitan University Hospital | Osaka , Japan, 545-8586Osaka General Medical Center | Osaka , Japan, 558-8558National Cerebral and Cardiovascular Center | Osaka , Japan, 564-8565Osaka Medical and Pharmaceutical University Hospital | Osaka , Japan, 569-8686Kitasato University Hospital | Sagamihara , Japan, 252-0375Saitama Medical University International Medical Center | Saitama , Japan, 350-1298Hamamatsu University Hospital | Shizuoka , Japan, 431-3192St. Luke's International Hospital | Tokyo , Japan, 104-8560Nippon Medical School Hospital | Tokyo , Japan, 113-8603The University of Tokyo Hospital | Tokyo , Japan, 113-8655Tokyo Women's Medical University Hospital | Tokyo , Japan, 162-8666Teikyo University Hospital | Tokyo , Japan, 173-8606P. Debyelaan 25 | Maastricht HX, Netherlands, 6229Amsterdam UMC, location AMC | Amsterdam , Netherlands, 1105Erasmus University Medical Center | Rotterdam , Netherlands, 3015Kardio Brynow Sp. z o.o. | Katowice , Poland, 40-555Unidade Local de Saude do Alto Ave, E.P.E | Creixomil Guimaraes, Portugal, 4835-044Unidade Local de Saude da Regiao de Aveiro, E.P.E. | Aveiro , Portugal, 3814-501Unidade Local de Saude de Sao Jose, E.P.E, - Hospital de Santa Marta Servico de Cardiologia | Lisbon , Portugal, 1150-199Hospital da Luz | Lisbon , Portugal, 1500-650Hospital CUF Descobertas, Lisbon, Cadiology Department | Lisbon , Portugal, 1998-018Complejo Hospitalario Universitario A Coruna | A Coruña , Spain, 15006Hospital de la Santa Creu i Sant Pau | Barcelona , Spain, 08025Hospital Clinic i Provincial de Barcelona | Barcelona , Spain, 08036Hospital General Universitario Gregorio Marañón (HGUGM), Calle del Doctor Esquerdo, 46. | Madrid , Spain, 28007Hospital Clinico San Carlos | Madrid , Spain, 28040Hospital Universitario Puerta de Hierro | Madrid , Spain, 28220Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos | Málaga , Spain, 29010Hospital Clinico Universitario Virgen de la | Murcia , Spain, 30120Hospital Son Llatzer | Palma de Mallorca , Spain, 07198Hospital Universitario de Salamanca | Salamanca , Spain, 37007Hospital Universitario Virgen Macarena | Seville , Spain, 41009Hospital Universitario Virgen del Rocio | Seville , Spain, 41013Hospital Alvaro Cunqueiro | Vigo , Spain, 36312NHS Tayside Ninewells Hospital & Medical School | Dundee Scotland, United Kingdom, DD1 9SYNHS Greater Glasgow and Clyde Queen Elizabeth University Hospital | Glasgow , United Kingdom, G51 4TFLiverpool Heart and Chest Hospital NHS Foundation Trust | Liverpool , United Kingdom, L14 3PEBarts Health NHS Trust St Bartholomew's Hospital | 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 (Ocmr) | Oxford , United Kingdom, OX3 9DU
Investigators
Study Director: Cytokinetics MD, Cytokinetics