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

NCT06081894 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CY 60332023-505797-15-00
• Study Type: interventional
• Target: 500
• Locations: 20 countries
• Sites: 180

Brief Summary

This clinical trial will study the effects of aficamten (versus placebo) on the quality of life, exercise capacity, and clinical outcomes of patients with non-obstructive hypertrophic cardiomyopathy.

Conditions

Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

Keywords

CK-3773274; CK-274; Aficamten; Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy; nHCM; ACACIA-HCM; ACACIA

Outcome Measures

Primary Outcomes (2)

• Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)

  Effect of aficamten compared with placebo on participant health status

  Baseline to Week 36

• Change in pVO2

  Effect of aficamten compared with placebo on maximal exercise capacity

  Baseline to Week 36

Secondary Outcomes (5)

• Change in composite of two Z-scores of CPET parameters (pVO2 and VE/VCO2 slope)

  Baseline to Week 36

• Proportion of participants with ≥ 1 class improvement in NYHA Functional Class

  Baseline to Week 36

• Change in NT-proBNP

  Baseline to Week 36

• Change in LAVI in participants without atrial fibrillation or flutter at baseline on ECG

  Baseline to Week 36

• Time to first CV event

  Baseline to End of Study, Week 72

Study Arms (2)

Aficamten

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive placebo, for up to 72 weeks.

Drug: Placebo

Interventions

Aficamten DRUG

Oral Tablet

Aficamten

Placebo DRUG

Oral Tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cytokinetics: lead
• Sanofi: collaborator
• Bayer: collaborator

Study Sites (180)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

UC San Diego Health - Sulpizio Cardiovascular Center

La Jolla, California, 92037, United States

Location

Keck Medical Center of USC (Outpatient Clinic)

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center (Smidt Heart Institute)

Los Angeles, California, 90048, United States

Location

UCLA Medical Center Cardiovascular Clinic

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06519, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Holy Cross Medical Group - Cardiology Associates

Fort Lauderdale, Florida, 33308, United States

Location

Investigational Drug Services, AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Piedmont Heart Institute (CPET)

Fayetteville, Georgia, 30214, United States

Location

The Queen's Medical Center-Punchbowl

Honolulu, Hawaii, 96813, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Ascension St. Vincent

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MedStar Union Memorial Hospital

Baltimore, Maryland, 21218, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01803, United States

Location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

M Health Fairview University of Minnesota Medical Center - East Bank

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Northwell Health North Shore University Hospital

Manhasset, New York, 11030, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Columbia University Medical Center/New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Sanger Heart & Vascular Institute - HCM Clinic

Charlotte, North Carolina, 28204, United States

Location

The Lindner Research Center at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Greenville Memorial Hospital

Greenville, South Carolina, 29605-5601, United States

Location

Ascension Saint Thomas Heart West

Nashville, Tennessee, 37205, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Utah Health

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Inova Health Care Services

Falls Church, Virginia, 22042, United States

Location

VCU Health Downtown Medical Campus

Richmond, Virginia, 23298, United States

Location

Carilion Clinic Cardiology

Roanoke, Virginia, 24014, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Providence Sacred Heart Medical Center & Children's Hospital (CPET)

Spokane, Washington, 99204, United States

Location

WVU Medicine

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin Hospitals and Clinics

Madison, Wisconsin, 53792, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Medical College of Wisconsin/Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Italiano de Buenos Aires Juan Domingo Peron

Buenos Aires, 119, Argentina

Location

ICBA - Instituto Cardiovascular de Buenos Aires

Buenos Aires, C1428, Argentina

Location

Hospital Privado Centro Medico de Cordoba S.A

Córdoba, X5016KEH, Argentina

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Flinders Medical Centre Cardiology Research

Adelaide, South Australia, 5042, Australia

Location

Fiona Stanley Hospital, AHF Unit

Murdoch, 6150, Australia

Location

Instituto D'Or de Pesquisa e Ensino/Cardio Pulmonar da Bahia SA

Ondina, Salvador, 40170-0130, Brazil

Location

Fundacao Felice Rocho / Hospital Felicio Rocho

Minas Gerais, 30110-934, Brazil

Location

NUPEC Cardio / Cardio HVC

Minas Gerais, 30220-140, Brazil

Location

CLINICOR Clinica Cardiologica LTDA

Ribeirão Preto, 14026-900, Brazil

Location

Instituto Dante Pazzanese de Cardiologia

São Paulo, 04012-909, Brazil

Location

Instituto do Coracao do Hospital de Aguiar

São Paulo, 05403-900, Brazil

Location

Associacao Lar Sao Francisco de Assis na Providencia de Deus - Hospital Universitario Sao Francisco na Providencia de Deus (HUSF)

São Paulo, 12916-542, Brazil

Location

Saraiva & Berlinger LTDA - EPP/IPECC - Instituto de Pesquisa Clinical de Campinas

São Paulo, 13060-080, Brazil

Location

Hospital das Clinicas de Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo - HCFMRP

São Paulo, 14051-140, Brazil

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

QEII Health Science Centre (Halifax Infirmary site)

Halifax, B3H 3A7, Canada

Location

The 1st Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Peking University First Hospital

Beijing, 100034, China

Location

Fuwai Hospital, CAMS & PUMC

Beijing, 100037, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 519041, China

Location

The First Hospital of Jilin University

Jilin, 130031, China

Location

Zhongda Hospital Southeast University

Nanjin, 210009, China

Location

Shanghai Ruijin Hospital Luwan Branch

Shanghai, 200020, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

People's Hospital of Liaoning Province

Shenyang, 110067, China

Location

Remin Hospital of Wuhan University

Wuhan, 430060, China

Location

The 1st affi. Hospital of Xi'an Jiaotong University

Xi'an, 710061, China

Location

The 1st affiliated Hospital of Zhengzhou University

Zhenzhou, 450052, China

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Department of Cardiology Copenhagen University Hospital, Bispebjerg

Copenhagen, 2400, Denmark

Location

Odense University Hospital, Department of Cardiology

Odense, 5000, Denmark

Location

Assistance Publique Hopitaux de Marseille

Marseille, 13005, France

Location

Clinique Du Millenaire

Montpellier, 34000, France

Location

Centre Hospitalier Universitaire De Montpellier

Montpellier, 34295, France

Location

Assistance Publique Hopitaux De Paris

Paris, 75010, France

Location

Assistance Publique Hopitaux de Paris

Paris, 75015, France

Location

Centre Hospitalier Universitaire De Bordeaux

Pessac, 33600, France

Location

Centre Hospitalier Universitaire De Nantes

Saint-Herblain, 44800, France

Location

Hopital Rangueil

Toulouse, 31059, France

Location

Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum (CVK) Medizinische Klinik mit Schwerpunkt Kardiologie

Berlin, 13353, Germany

Location

Herzzentrum der Universitatsmedizin Gottingen

Göttingen, 37075, Germany

Location

Universitaesklinkum Heidelberg Klinik fuer Kardiologie, Angeiologie und Pneumologie

Heidelberg, 69120, Germany

Location

Univeristy Hospital Jena Clinic for Internal Medicine I (Cardiology, Angiology, Internal Intensive Care Medicine)

Jena, 07747, Germany

Location

Evangelismos General Hospital of Athens

Athens, 10676, Greece

Location

"Hippokration" General Hospital of Athens

Athens, 11527, Greece

Location

University General Hospital Attikon

Attiki, 12462, Greece

Location

Onassis Cardiac Surgery Center

Kallithea, 17674, Greece

Location

Semmelweis Egyetem Varosmajori Sziv- es Ergyogyaszati Klinika

Budapest, 1122, Hungary

Location

University of Szeged

Szeged, 6725, Hungary

Location

Landspitali University Hospital

Reykjavik, 101, Iceland

Location

The Barzilai University Medical Center 2 - Cardiology Division

Ashkelon, 7830604, Israel

Location

Division of Cardiology Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

The Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Ziv Medical Center

Safed, 1311001, Israel

Location

Cardiology Department IRCCS San Donato Hospital - University of Milan

San Donato Milanese, Milano, 20097, Italy

Location

UOC Cardiologica

Brescia, 25123, Italy

Location

Azienda Ospedaliera Universitaria Careggi pad. 13 Clinica Medica II Plano Cardiologia

Florence, 50134, Italy

Location

Cardiologia Universitaria - UTIC - Riabilitazione Cardiologica Azienda Ospedaliero Universitaria - Ospedali Riuniti

Foggia, 71122, Italy

Location

Unita Operativa di Riabilitazione Cardiologica, Istituto Auxologico Italiano, IRCCS - Auxologico San Luca, Piazzale Brescia, 20

Milan, 20149, Italy

Location

Dipartimento Cardio-toraco- vascolare, ASST Grande Ospedale Metropolitano, NiguardaPiazza Ospedale Maggiore, 3

Milan, 20162, Italy

Location

Dipartimento di Emergenze Cardiovascolari, Medicina Clinica e dell'Invecchiamento, AOU Federico II

Naples, 80131, Italy

Location

Fondazione 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, 56124, Italy

Location

Dipartimento Cardiopolmonare, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele

Roma, 00163, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina Trieste SC Cardiologia

Trieste, 34148, Italy

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Kobe City Medical Center General Hospital

Hyōgo, 650{047, Japan

Location

Hyogo Prefectural Harima-Himeii General Medical Center

Hyōgo, 670-8560, Japan

Location

University of Tsukuba Hospital

Ibaraki, 305-8576, Japan

Location

SHOWA Medical University Fujigaoka Hospital

Kanagawa, 227-8501, Japan

Location

Kochi Medical School Hospital

Kochi, 783-8505, Japan

Location

National Hospital Organization Kyoto Medical Center

Kyoto, 612-0861, Japan

Location

Mie University Hospital

Mie, 514-8507, Japan

Location

National University Corporation Tohoku University Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

Shinshu University Hospital

Nagano, 390-8621, Japan

Location

Osaka Metropolitan University Hospital

Osaka, 545-8586, Japan

Location

Osaka General Medical Center

Osaka, 558-8558, Japan

Location

National Cerebral and Cardiovascular Center

Osaka, 564-8565, Japan

Location

Osaka Medical and Pharmaceutical University Hospital

Osaka, 569-8686, Japan

Location

Kitasato University Hospital

Sagamihara, 252-0375, Japan

Location

Saitama Medical University International Medical Center

Saitama, 350-1298, Japan

Location

Hamamatsu University Hospital

Shizuoka, 431-3192, Japan

Location

St. Luke's International Hospital

Tokyo, 104-8560, Japan

Location

Nippon Medical School Hospital

Tokyo, 113-8603, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, 162-8666, Japan

Location

Teikyo University Hospital

Tokyo, 173-8606, Japan

Location

P. Debyelaan 25

Maastricht, HX, 6229, Netherlands

Location

Amsterdam UMC, location AMC

Amsterdam, 1105, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015, Netherlands

Location

Kardio Brynow Sp. z o.o.

Katowice, 40-555, Poland

Location

Unidade Local de Saude do Alto Ave, E.P.E

Creixomil, Guimaraes, 4835-044, Portugal

Location

Unidade Local de Saude da Regiao de Aveiro, E.P.E.

Aveiro, 3814-501, Portugal

Location

Unidade Local de Saude de Sao Jose, E.P.E, - Hospital de Santa Marta Servico de Cardiologia

Lisbon, 1150-199, Portugal

Location

Hospital da Luz

Lisbon, 1500-650, Portugal

Location

Hospital CUF Descobertas, Lisbon, Cadiology Department

Lisbon, 1998-018, Portugal

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, 15006, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañón (HGUGM), Calle del Doctor Esquerdo, 46.

Madrid, 28007, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28220, Spain

Location

Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos

Málaga, 29010, Spain

Location

Hospital Clinico Universitario Virgen de la

Murcia, 30120, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, 36312, Spain

Location

NHS Tayside Ninewells Hospital & Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

NHS Greater Glasgow and Clyde Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Liverpool Heart and Chest Hospital NHS Foundation Trust

Liverpool, L14 3PE, United Kingdom

Location

Barts Health NHS Trust St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

St George's University Hospitals NHS Foundation Trust,

London, SW17 0QT, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Oxford Centre for Clinical Magnetic Resonance Research (Ocmr)

Oxford, OX3 9DU, United Kingdom

Location

Study Officials

• Cytokinetics MD

  Cytokinetics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: October 13, 2023
• Study Start: August 30, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (7); PT (5); NL (3); JP (22); ES (13); IT (10); AU (3); GR (4); CN (12); HU (2); IC (1); DK (3); US (60); CA (5); DE (4); AR (3); FR (8); IL (5); PL (1); BR (9)