A Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM)
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
Sex
ALL
Min age
18 Years
Max age
85 Years
Healthy volunteers
No
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 outcome measure(s)
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
Trial sites (180)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
UC San Diego Health - Sulpizio Cardiovascular Center
La Jolla
California
Keck Medical Center of USC (Outpatient Clinic)
Los Angeles
California
Cedars-Sinai Medical Center (Smidt Heart Institute)
Los Angeles
California
UCLA Medical Center Cardiovascular Clinic
Los Angeles
California
University of California San Francisco
San Francisco
California
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance
California
Yale New Haven Hospital
New Haven
Connecticut
MedStar Washington Hospital Center
Washington D.C.
District of Columbia
Holy Cross Medical Group - Cardiology Associates
Fort Lauderdale
Florida
Investigational Drug Services, AdventHealth Orlando
Orlando
Florida
Emory Clinic
Atlanta
Georgia
Piedmont Heart Institute (CPET)
Fayetteville
Georgia
The Queen's Medical Center-Punchbowl
Honolulu
Hawaii
Northwestern University
Evanston
Illinois
Ascension St. Vincent
Indianapolis
Indiana
University of Iowa Hospitals and Clinics
Iowa City
Iowa
The University of Kansas Medical Center
Kansas City
Kansas
MedStar Union Memorial Hospital
Baltimore
Maryland
Massachusetts General Hospital
Boston
Massachusetts
Brigham and Women's Hospital
Boston
Massachusetts
Lahey Hospital & Medical Center
Burlington
Massachusetts
Michigan Medicine
Ann Arbor
Michigan
Henry Ford Hospital
Detroit
Michigan
M Health Fairview University of Minnesota Medical Center - East Bank
Minneapolis
Minnesota
Mayo Clinic
Rochester
Minnesota
Saint Luke's Hospital of Kansas City
Kansas City
Missouri
Morristown Medical Center
Morristown
New Jersey
Northwell Health North Shore University Hospital
Manhasset
New York
NYU Langone Health
New York
New York
Weill Cornell Medicine
New York
New York
Mount Sinai Hospital
New York
New York
Columbia University Medical Center/New York Presbyterian Hospital
New York
New York
Westchester Medical Center
Valhalla
New York
Sanger Heart & Vascular Institute - HCM Clinic
Charlotte
North Carolina
The Lindner Research Center at The Christ Hospital
Cincinnati
Ohio
University Hospitals Cleveland Medical Center
Cleveland
Ohio
Cleveland Clinic
Cleveland
Ohio
Providence St. Vincent Medical Center
Portland
Oregon
Oregon Health & Science University
Portland
Oregon
+ 140 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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