Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM)
NCT ID: NCT05186818
Last Updated: 2025-02-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
282 participants
INTERVENTIONAL
2022-02-01
2023-12-18
Brief Summary
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Detailed Description
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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 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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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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.
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.
Placebo to match aficamten
Placebo tablets were administered orally once daily.
Interventions
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Aficamten (5 mg, 10 mg, 15 mg, and 20 mg)
Aficamten tablets were administered orally once daily.
Placebo to match aficamten
Placebo tablets were administered orally once daily.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
Exclusion Criteria
* 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.
18 Years
85 Years
ALL
No
Sponsors
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Corxel Pharmaceuticals
INDUSTRY
Cytokinetics
INDUSTRY
Responsible Party
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Principal Investigators
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Cytokinetics MD
Role: STUDY_DIRECTOR
Cytokinetics
Locations
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Alaska Heart and Vascular Institute
Anchorage, Alaska, United States
UC San Diego Health - Sulpizio Cardiovascular Center
La Jolla, California, United States
Cedars-Sinai Medical Center - Smidt Heart Institute Clinic
Los Angeles, California, United States
University of California San Francisco
San Francisco, California, United States
Stanford University Hospital
Stanford, California, United States
Yale School of Medicine
New Haven, Connecticut, United States
Yale University School of Medicine
New Haven, Connecticut, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
Holy Cross Hospital / Cardiology Associates
Fort Lauderdale, Florida, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
Emory Clinic
Atlanta, Georgia, United States
Piedmont Fayette Hospital
Fayetteville, Georgia, United States
Northwestern University
Chicago, Illinois, United States
University of Iowa
Iowa City, Iowa, United States
MedStar Medical Group Cardiology at Union Memorial
Baltimore, Maryland, United States
Medstar Franklin Square Medical Center
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, 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 Medical Center
Detroit, Michigan, United States
Spectrum Health Medical Group Cardiovascular Medicine
Grand Rapids, Michigan, United States
M Health Fairview University of Minnesota Medical Center - East Bank
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Morristown Medical Center
Morristown, New Jersey, United States
NYU Langone Health
New York, New York, United States
Mount Sinai Hospital
New York, New York, United States
Columbia University Medical Center/NY Presbyterian Hospital
New York, New York, United States
Westchester Medical Center
Valhalla, New York, United States
Sanger Heart and Vascular Institute
Charlotte, North Carolina, United States
Sanger Heart and Vascular Institute - HCM Clinic
Charlotte, North Carolina, United States
Duke Health Center Arringdon
Morrisville, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Ascension St. John Clinical Research Institute
Tulsa, Oklahoma, United States
Oregon Health & Science University
Portland, Oregon, United States
Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)
Philadelphia, Pennsylvania, United States
UPMC Presbyterian
Pittsburgh, Pennsylvania, United States
Stern Cardiovascular Foundation, Inc
Germantown, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
The University of Texas Southwestern Medical Center
Dallas, Texas, United States
Houston Methodist Hospital
Houston, Texas, United States
University of Utah Hospital
Salt Lake City, Utah, United States
University of Virginia Health System University Hospital
Charlottesville, Virginia, United States
University of Washington Medical
Seattle, Washington, United States
Froedtert Hospital
Milwaukee, Wisconsin, United States
Beijing Chao-Yang Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Beijing Anzhen Hospital
Beijing, Beijing Municipality, China
Peking University Third Hospital
Beijing, Beijing Municipality, China
Nanfang Hospital Southern Medical University
Guanzhou, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
Xiangya Hospital of the Central South University
Changsha, Hunan, China
The First Hospital of Jinlin University
Changchun, Jinlin, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, China
Charles University
Prague, , Czechia
Interni klinika kardiologie a angiologie
Prague, , Czechia
Aalborg University Hospital, Department of Cardiology
Aalborg, , Denmark
Department of Cardiology Aarhus University Hospital
Aarhus, , Denmark
Hjertecentret (The Heart Center)
Copenhagen, , Denmark
Copenhagen University Hospital
Copenhagen, , Denmark
Hopital Universitaire de Rangueil (CHU de Toulouse) Service de Cardiologie
Toulouse, Cedex, France
CHU de Marseille - Hopital de la Timone Service de cardiologie
Marseille, , France
CHU de Nantes
Nantes, , France
Hopital Lariboisiere, Service de Cardiologie
Paris, , France
Hôpital Européen Georges Pompidou
Paris, , France
CHU Pitie-Salpetriere, Centre de reference maladies cardiaques hereditaires ou rares
Paris, , France
CHU de Bordeaux Hopital Cardiologique Haut-Leveque
Pessac, , France
CHU du Haut Lveque Cardiologie
Pessac, , France
Kerckhoff-Klinik GmbH Abteilung Administration Forschung und Lehre
Bad Nauheim, , Germany
Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum (CVK) Medizinische Klinik mit Schwerpunkt Kardiologie
Berlin, , Germany
Universitaetsklinikum Essen Westdeutsches Herz-Gefaesszentrum
Essen, , Germany
Klinikumder Georg-August-Universitaet
Göttingen, , Germany
Universitaetsmedizin Goettingen
Göttingen, , Germany
Universitaetsklinikum Heidelberg
Heidelberg, , Germany
Universitaetsklinikum Jena Klinik fuer Innere Medizin 1
Jena, , Germany
Unniversitaetsklinikum Magdeburg Klinik fur Kardiologie und Anglologie
Magdeburg, , Germany
Universitätsklinikum 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
The Barzilai University Medical Center
Ashkelon, , Israel
The Barzilai University Medical Center
Ashkelon, , Israel
Hadassah Medical Center- Ein Kerem
Jerusalem, , Israel
Kaplan Medical Center
Rehovot, , Israel
Ziv Medical Center
Safed, , Israel
UOC Cardiologica Azienda Ospedaliera Spedali Civili di Brescia
Brescia, , Italy
Azienda Ospedaliero Universitaria Careggi Dipartimento Cardiotoracovascolare - Cardiomiopatie Unit
Florence, , Italy
Fondazione toscana Gabriele Monesterio per la ricarca medica Dipartimento Cardiotoracico UOC Cardiologia e Medicina Cardiovasculare Ospedale San Cataldo
Pisa, , Italy
Dipartimento di Medicina Clinica e Molecolare Universita Sapienza di Roma Unita di Terapia Intensiva Cardiologica Azienda Ospedaliero Universitaria Sant'Andrea
Roma, , Italy
Amsterdam UMC, location AMC
Amsterdam, , Netherlands
University Hospital Maastricht
Maastricht, , Netherlands
Erasmus Medical Center
Rotterdam, , Netherlands
Narodowy Instytut Kardiologii Stefana Kardynała Wyszynskiego- Panstwowy Instytut Badawczy
Warsaw, Masovian Voivodeship, Poland
Kardio Brynow S.C
Katowice, , Poland
Krakowskie Centrum
Krakow, , Poland
Centro Hospitalar Do Baixo Vouga, EPE AV ARTUR RAVARA
Aveiro, , Portugal
Hospital da Luz
Lisbon, , Portugal
Complejo Hospitalario Universitario
A Coruña, La Coruna, Spain
Hospital Universitario Puerta de Hierro
Madrid, Majadahonda, Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Hospital Clinico Universitario Virgen de la Arrixaca
Murcia, , Spain
Hospital Universitario Son Llatzer Secretaria de Cardiologia
Palma, , Spain
Hospital Universitario de Salamanca
Salamanca, , Spain
Hospital Universitario Virgen Macarena-merge
Seville, , Spain
Queen Elizabeth Hospital Birmingham University Hospitals Birmingham NHS Foundation Trust
Edgbaston, Birmingham, United Kingdom
Queen Elizabeth University Hospital - HWS Greater Glasgow and Clyde
Glasgow, , United Kingdom
Liverpool Heart and Chest Hospital - Liverpool Heart and Chest Hospital NHS Foundation Trust- HWS Greater Glasgow and Clyde
Liverpool, , United Kingdom
Barts Health NS Trust
London, , United Kingdom
St George's University Hospitals NHS Foundation Trust
London, , United Kingdom
Royal Brompton Hospital
London, , United Kingdom
Oxford Centre for Clinical Magnetic Resonance Research
Oxford, , United Kingdom
Radcliffe Department of Medicine
Oxford, , United Kingdom
Countries
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References
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Campain J, Griskowitz C, Newlands C, Claggett BL, Kulac IJ, McGinnis S, Giverts I, Moreno F, Minasian A, Prasad C, Rupert L, Landsteiner I, Iskenderian N, Coats CJ, Lee MMY, Maron MS, Owens AT, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Wohltman A, Malhotra R, Lewis GD. Characterization and Application of Novel Exercise Recovery Patterns That Reflect Cardiac Performance: A Substudy of the SEQUOIA-HCM Trial. Circulation. 2025 Oct 7;152(14):990-1002. doi: 10.1161/CIRCULATIONAHA.124.073585. Epub 2025 Sep 5.
Maron MS, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Arad M, Cardim N, Choudhury L, Claggett B, Coats CJ, Dungen HD, Garcia-Pavia P, Hagege AA, Januzzi JL, Kulac I, Lee MMY, Lewis GD, Ma CS, Michels M, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins HC, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Olivotto I; SEQUOIA-HCM Investigators. Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Coll Cardiol. 2024 Nov 5;84(19):1821-1831. doi: 10.1016/j.jacc.2024.09.003. Epub 2024 Sep 30.
Lee MMY, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Claggett BL, Coats CJ, Gimeno JR, Kulac IJ, Landsteiner I, Ma C, Maron MS, Olivotto I, Owens AT, Solomon SD, Veselka J, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Lewis GD; SEQUOIA-HCM Investigators. Aficamten and Cardiopulmonary Exercise Test Performance: A Substudy of the SEQUOIA-HCM Randomized Clinical Trial. JAMA Cardiol. 2024 Nov 1;9(11):990-1000. doi: 10.1001/jamacardio.2024.2781.
Sherrod CF 4th, Saberi S, Nassif ME, Claggett BL, Coats CJ, Garcia-Pavia P, Januzzi JL, Lewis GD, Ma C, Maron MS, Miao ZM, Olivotto I, Veselka J, Butzner M, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Spertus JA. Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Coll Cardiol. 2024 Nov 5;84(19):1773-1785. doi: 10.1016/j.jacc.2024.08.014. Epub 2024 Sep 1.
Masri A, Cardoso RN, Abraham TP, Claggett BL, Coats CJ, Hegde SM, Kulac IJ, Lee MMY, Maron MS, Merkely B, Michels M, Olivotto I, Oreziak A, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Solomon SD, Wohltman A, Kwong RY, Kramer CM; SEQUOIA-HCM Investigators. Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM CMR Substudy. J Am Coll Cardiol. 2024 Nov 5;84(19):1806-1817. doi: 10.1016/j.jacc.2024.08.015. Epub 2024 Sep 1.
Hegde SM, Claggett BL, Wang X, Jering K, Prasad N, Roshanali F, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Cardim N, Coats CJ, Kramer CM, Maron MS, Michels M, Olivotto I, Saberi S, Jacoby DL, Heitner SB, Kupfer S, Meng L, Wohltman A, Malik FI, Solomon SD; SEQUOIA-HCM Investigators. Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2024 Nov 5;84(19):1789-1802. doi: 10.1016/j.jacc.2024.08.002. Epub 2024 Sep 1.
Coats CJ, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, Choudhury L, Claggett B, Dungen HD, Garcia-Pavia P, Hagege AA, Januzzi JL, Lee MMY, Lewis GD, Ma CS, Maron MS, Miao ZM, Michels M, Olivotto I, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins H, Jacoby DL, German P, Heitner SB, Kupfer S, Lutz JD, Malik FI, Meng L, Wohltman A, Abraham TP; SEQUOIA-HCM Investigators *. Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. J Am Heart Assoc. 2024 Aug 6;13(15):e035993. doi: 10.1161/JAHA.124.035993. Epub 2024 Jul 26.
Maron MS, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, Choudhury L, Claggett B, Coats CJ, Dungen HD, Garcia-Pavia P, Hagege AA, Januzzi JL, Lee MMY, Lewis GD, Ma CS, Michels M, Olivotto I, Oreziak A, Owens AT, Spertus JA, Solomon SD, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins H, Jacoby DL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Abraham TP; SEQUOIA-HCM Investigators. Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2024 May 30;390(20):1849-1861. doi: 10.1056/NEJMoa2401424. Epub 2024 May 13.
Coats CJ, Maron MS, Abraham TP, Olivotto I, Lee MMY, Arad M, Cardim N, Ma CS, Choudhury L, Dungen HD, Garcia-Pavia P, Hagege AA, Lewis GD, Michels M, Oreziak A, Owens AT, Tfelt-Hansen J, Veselka J, Watkins HC, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Meng L, Wohltman A, Masri A; SEQUOIA-HCM Investigators. Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design. JACC Heart Fail. 2024 Jan;12(1):199-215. doi: 10.1016/j.jchf.2023.10.004. Epub 2023 Nov 29.
Other Identifiers
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2021-003536-92
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CY 6031
Identifier Type: -
Identifier Source: org_study_id
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