Clinical trial NCT06081894: Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM
Official title: A 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
Keywords: CK-3773274
CK-274
Aficamten
Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
nHCM
ACACIA-HCM
ACACIA
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
name: Bayer
First posted: 2023-10-13
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

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