Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
- Conditions
- Obstructive Hypertrophic Cardiomyopathy (oHCM)
- Interventions
- Registration Number
- NCT05767346
- Lead Sponsor
- Cytokinetics
- Brief Summary
The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 170
-
Participants who meet all the following criteria at screening may be included in the trial:
-
Males and females between 18 to 85 years of age, inclusive, at screening
-
Body mass index < 35 kg/m2
-
Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography -
-
Has left ventricular (LV) hypertrophy with 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:
- ≥ 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
-
-
NYHA class II or III
-
Has a KCCQ-CSS score of ≤ 90 at screening
-
Has a screening echocardiogram with the following determined by the echocardiography core laboratory:
- Resting LVOT-G > 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND
- LVEF ≥ 60%
-
Hemoglobin ≥ 10g/dL
-
Respiratory exchange ratio (RER) ≥ 1.05 and peak oxygen uptake (pVO2) < 100% predicted on the screening CPET per the core laboratory
-
Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks
-
-
Any of the following criteria will exclude potential participants from the trial:
-
Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM
-
History of intolerance or medical contraindication to beta blocker therapy
-
Resting SBP of > 160 mmHg
-
Resting heart rate of > 100 bpm
-
Significant valvular heart disease
- Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
- Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment)
-
Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
-
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)
-
Documented room air oxygen saturation reading < 90% at screening
-
Planned septal reduction treatment that cannot be deferred during the trial period
-
History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening
-
History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed.
-
Current or recent (< 4 weeks) therapy with disopyramide
-
History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
-
Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten
-
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metoprolol succinate up to 200 mg plus placebo for aficamten Metoprolol succinate (50 mg, 100 mg, 150 mg and 200 mg) Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks. Aficamten up to 20 mg plus placebo for metoprolol Aficamten (CK-3773274) (5 mg, 10 mg, 15 mg and 20 mg) Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks. Aficamten up to 20 mg plus placebo for metoprolol Placebo to match metoprolol succinate Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks. Metoprolol succinate up to 200 mg plus placebo for aficamten Placebo to match aficamten Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.
- Primary Outcome Measures
Name Time Method Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET) Baseline to Week 24 Effect of aficamten compared with metoprolol succinate on exercise capacity in patients with symptomatic oHCM
- Secondary Outcome Measures
Name Time Method Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class Baseline to Week 24 Effect of aficamten compared with metoprolol succinate on NYHA Functional Classification
Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) Baseline to Week 24 Effect of aficamten compared with metoprolol succinate on participant health status
Change in left ventricular mass index (LVMI) Baseline to Week 24 Effect of aficamten on mass of the heart as compared with metoprolol succinate
Change in left atrial volume index (LAVI) Baseline to Week 24 Effect of aficamten on size of the heart as compared with metoprolol succinate
Change from baseline values in NT-proBNP Baseline to Week 24 Effect of aficamten on NT-proBNP as compared with metoprolol succinate
Change in post-Valsalva LVOT-G Baseline to Week 24 Effect of aficamten on post-Valsalva LVOT-G as compared with metoprolol succinate
Trial Locations
- Locations (71)
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Universitaetsklinikum Jena
🇩🇪Jena, Germany
Charite-Universitatsmedizin Berlin - Campus Virchow Klinikum
🇩🇪Berlin, Germany
Copenhagen University Hospital
🇩🇰Copenhagen, Denmark
CHU La Timone
🇫🇷Marseille, France
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
Hopital Lariboisiere - APHP
🇫🇷Paris, France
Hopital Cardiologique Haut Leveque - CHU de Bordeaux
🇫🇷Pessac, France
CHU Pontchaillou
🇫🇷Rennes, France
Alaska Heart and Vascular Institute
🇺🇸Anchorage, Alaska, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
UC San Diego Health - Sulpizio Cardiovascular Center
🇺🇸La Jolla, California, United States
Cedars-Sinai Medical Center (Smidt Heart Institute)
🇺🇸Los Angeles, California, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
AdventHealth
🇺🇸Orlando, Florida, United States
Emory Clinic
🇺🇸Atlanta, Georgia, United States
Piedmont Fayette Hospital
🇺🇸Fayetteville, Georgia, United States
Northwestern University
🇺🇸Evanston, Illinois, 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
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Columbia University Medical Center/New York Presbyterian Hospital
🇺🇸New York, New York, United States
Sanger Heart & Vascular Institute - HCM Clinic
🇺🇸Charlotte, North Carolina, United States
Duke Health Center Arringdon
🇺🇸Morrisville, North Carolina, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)
🇺🇸Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Ascension Saint Thomas Heart West
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
CHI St. Luke's Health Baylor-St. Luke's Medical Center
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Inova Schar Heart and Vascular
🇺🇸Falls Church, Virginia, United States
Instituto de Pesquisa Clinica de Campinas - IPECC
🇧🇷Campinas, SP, Brazil
lnstituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
🇧🇷San Paolo, SP, Brazil
Institutdo Danta Pazzanese
🇧🇷Ibirapuera, Brazil
Institut universitaire de cardiologie et de pneumonlogie de Quebec - Universite Laval
🇨🇦Québec, Canada
Xiangya Second Hospital of Central South University
🇨🇳Changsha, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Hopital Laennec - CHU de Nantes
🇫🇷Saint-Herblain, France
Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika
🇭🇺Budapest, Hungary
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Hadassah Hebrew Medical Center- Ein Kerem
🇮🇱Jerusalem, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Ziv Medical Center
🇮🇱Safed, Israel
AOU Careggi
🇮🇹Florence, Italy
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Complejo Hospitalario Universitario A Coruna
🇪🇸A Coruña, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Clinico Universitario Virgen Arrixaca
🇪🇸El Palmar, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Son Llatzer
🇪🇸Son Ferriol, Spain
NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
Liverpool Heart and Chest Hospital NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
Royal Brompton Hospital
🇬🇧London, United Kingdom
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
Oxford University Hospital NHS Trust - John Radcliffe Hospital - OCMR
🇬🇧Oxford, United Kingdom