Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM
- Conditions
- Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
- Interventions
- Drug: Placebo
- Registration Number
- NCT06081894
- Lead Sponsor
- Cytokinetics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
-
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
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aficamten 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. Placebo Placebo Participants in this arm will receive placebo, for up to 72 weeks.
- Primary Outcome Measures
Name Time Method Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) Baseline to Week 36 Effect of aficamten compared with placebo on participant health status
Change in pVO2 Baseline to Week 36 Effect of aficamten compared with placebo on maximal exercise capacity
- Secondary Outcome Measures
Name Time Method Change in composite of two Z-scores of CPET parameters (pVO2 and VE/VCO2 slope) Baseline to Week 36 Effect of aficamten compared with placebo on global exercise capacity based on maximal and sub-maximal exercise performance
Proportion of participants with ≥ 1 class improvement in NYHA Functional Class Baseline to Week 36 Effect of aficamten compared with placebo on NYHA Functional Classification
Change in NT-proBNP Baseline to Week 36 Effect of aficamten compared with placebo on a biomarker of cardiac wall stress
Change in LAVI Baseline to Week 36 Effect of aficamten compared with placebo on echocardiographic measures of structural remodeling
Time to first CV event Baseline to End of Study, Week 72 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)
Trial Locations
- Locations (135)
Hospital Italiano de Buenos Aires Juan Domingo Peron
🇦🇷Buenos Aires, Argentina
Fiona Stanley Hospital, AHF Unit
🇦🇺Murdoch, Australia
Instituto D'Or de Pesquisa e Ensino/Cardio Pulmonar da Bahia SA
🇧🇷Ondina, Salvador, Brazil
QEII Health Science Centre (Halifax Infirmary site)
🇨🇦Halifax, Canada
Peking University First Hospital
🇨🇳Beijing, China
Fuwai Hospital, CAMS & PUMC
🇨🇳Beijing, China
The 1st affiliated Hospital of Zhengzhou University
🇨🇳Zhenzhou, China
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Department of Cardiology Copenhagen University Hospital, Bispebjerg
🇩🇰Copenhagen, Denmark
Odense University Hospital, Department of Cardiology
🇩🇰Odense, Denmark
Assistance Publique Hopitaux De Paris
🇫🇷Paris, France
Centre Hospitalier Universitaire De Bordeaux
🇫🇷Pessac, France
Centre Hospitalier Universitaire De Nantes
🇫🇷Saint-Herblain, France
Hopital Rangueil
🇫🇷Toulouse, France
Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum (CVK) Medizinische Klinik mit Schwerpunkt Kardiologie
🇩🇪Berlin, Germany
Herzzentrum der Universitatsmedizin Gottingen
🇩🇪Göttingen, Germany
Universitaesklinkum Heidelberg Klinik fuer Kardiologie, Angeiologie und Pneumologie
🇩🇪Heidelberg, Germany
Univeristy Hospital Jena Clinic for Internal Medicine I (Cardiology, Angiology, Internal Intensive Care Medicine)
🇩🇪Jena, Germany
Semmelweis Egyetem Varosmajori Sziv- es Ergyogyaszati Klinika
🇭🇺Budapest, Hungary
University of Szeged
🇭🇺Szeged, Hungary
Meir Medical Center
🇮🇱Kfar Saba, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Cardiology Department IRCCS San Donato Hospital - University of Milan
🇮🇹San Donato Milanese, Milano, Italy
UOC Cardiologica
🇮🇹Brescia, Italy
Azienda Ospedaliera Universitaria Careggi pad. 13 Clinica Medica II Plano Cardiologia
🇮🇹Firenze, Italy
Cardiologia Universitaria - UTIC - Riabilitazione Cardiologica Azienda Ospedaliero Universitaria - Ospedali Riuniti
🇮🇹Foggia, Italy
Dipartimento di Emergenze Cardiovascolari, Medicina Clinica e dell'Invecchiamento, AOU Federico II
🇮🇹Napoli, Italy
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, Italy
Dipartimento Cardiopolmonare, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
🇮🇹Roma, Italy
Azienda Sanitaria Universitaria Giuliano Isontina Trieste SC Cardiologia
🇮🇹Trieste, Italy
Amsterdam UMC, location AMC
🇳🇱Amsterdam, Netherlands
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
Kardio Brynow Sp. z o.o.
🇵🇱Katowice, Poland
Unidade Local de Saude da Regiao de Aveiro, E.P.E.
🇵🇹Aveiro, Portugal
Unidade Local de Saude de Sao Jose, E.P.E, - Hospital de Santa Marta Servico de Cardiologia
🇵🇹Lisboa, Portugal
Hospital da Luz
🇵🇹Lisboa, Portugal
Hospital CUF Descobertas, Lisbon, Cadiology Department
🇵🇹Lisbon, Portugal
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario A Coruna
🇪🇸Coruña, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la
🇪🇸Murcia, Spain
Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos
🇪🇸Málaga, Spain
Hospital Son Llatzer
🇪🇸Palma De Mallorca, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Alaska Heart and Vascular Institute
🇺🇸Anchorage, Alaska, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
MedStar Union Memorial Hospital
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
M Health Fairview University of Minnesota Medical Center - East Bank
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Spain
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
UC San Diego Health - Sulpizio Cardiovascular Center
🇺🇸La Jolla, California, United States
St George's University Hospitals NHS Foundation Trust,
🇬🇧London, United Kingdom
Oxford Centre for Clinical Magnetic Resonance Research (Ocmr)
🇬🇧Oxford, United Kingdom
Cedars-Sinai Medical Center (Smidt Heart Institute)
🇺🇸Los Angeles, California, United States
Arizona Cardiovascular Research Center
🇺🇸Las Vegas, Nevada, United States
NYU Langone Health
🇺🇸New York, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Instituto Dante Pazzanese de Cardiologia
🇧🇷São Paulo, Brazil
Instituto do Coracao do Hospital de Aguiar
🇧🇷São Paulo, Brazil
Associacao Lar Sao Francisco de Assis na Providencia de Deus - Hospital Universitario Sao Francisco na Providencia de Deus (HUSF)
🇧🇷São Paulo, Brazil
Saraiva & Berlinger LTDA - EPP/IPECC - Instituto de Pesquisa Clinical de Campinas
🇧🇷São Paulo, Brazil
Hospital das Clinicas de Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo - HCFMRP
🇧🇷São Paulo, Brazil
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
The First Hospital of Jilin University
🇨🇳Jilin, China
Zhongda Hospital Southeast University
🇨🇳Nanjin, China
Shanghai Ruijin Hospital Luwan Branch
🇨🇳Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
People's Hospital of Liaoning Province
🇨🇳Shenyang, China
University of California San Francisco
🇺🇸San Francisco, California, United States
Ascension St. Vincent
🇺🇸Indianapolis, Indiana, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Investigational Drug Services, AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Holy Cross Medical Group - Cardiology Associates
🇺🇸Fort Lauderdale, Florida, United States
Emory Clinic
🇺🇸Atlanta, Georgia, United States
Piedmont Heart Institute (CPET)
🇺🇸Fayetteville, Georgia, United States
The Queen's Medical Center-Punchbowl
🇺🇸Honolulu, Hawaii, United States
Northwestern University
🇺🇸Evanston, Illinois, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Lahey Hospital & Medical Center
🇺🇸Burlington, Massachusetts, United States
Michigan Medicine
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Columbia University Medical Center/New York Presbyterian Hospital
🇺🇸New York, New York, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
UPMC Presbyterian
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Westchester Medical Center
🇺🇸Valhalla, New York, United States
Sanger Heart & Vascular Institute - HCM Clinic
🇺🇸Charlotte, North Carolina, United States
The Lindner Research Center at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
Ascension Saint Thomas Heart West
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Inova Health Care Services
🇺🇸Falls Church, Virginia, United States
Carilion Clinic Cardiology
🇺🇸Roanoke, Virginia, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Providence Sacred Heart Medical Center & Children's Hospital (CPET)
🇺🇸Spokane, Washington, United States
WVU Medicine
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin Hospitals and Clinics
🇺🇸Madison, Wisconsin, United States
Medical College of Wisconsin/Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Flinders Medical Centre Cardiology Research
🇦🇺Adelaide, South Australia, Australia
Fundacao Felice Rocho / Hospital Felicio Rocho
🇧🇷Minas Gerais, Brazil
NUPEC Cardio / Cardio HVC
🇧🇷Minas Gerais, Brazil
Remin Hospital of Wuhan University
🇨🇳Wuhan, China
The 1st affi. Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, China
Assistance Publique Hopitaux de Marseille
🇫🇷Marseille, France
Clinique Du Millenaire
🇫🇷Montpellier, France
Centre Hospitalier Universitaire De Montpellier
🇫🇷Montpellier, France
Assistance Publique Hopitaux de Paris
🇫🇷Paris, France
The Barzilai University Medical Center 2 - Cardiology Division
🇮🇱Ashkelon, Israel
Division of Cardiology Hadassah Medical Center
🇮🇱Jerusalem, Israel
Ziv Medical Center
🇮🇱Safed, Israel
NHS Tayside Ninewells Hospital & Medical School
🇬🇧Dundee, Scotland, United Kingdom
NHS Greater Glasgow and Clyde Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Barts Health NHS Trust St Bartholomew's Hospital
🇬🇧London, United Kingdom
Royal Brompton Hospital
🇬🇧London, United Kingdom