The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
Eligibility
Sex
ALL
Min age
12 Years
Max age
17 Years
Healthy volunteers
No
Inclusion Criteria:
* Period 1: Treatment Period
* Males and females between 12 and \< 18 years of age at screening and at Day 1.
* Body weight ≥ 35 kg
* Diagnosed with oHCM based on the following at screening:
* Left ventricular (LV) hypertrophy with nondilated LV chamber in the absence of other cardiac disease.
* Core laboratory confirmation of LV end-diastolic wall thickness that meets a threshold of:
* Z-score \> 2.5 in the absence of family history OR
* Z-score \> 2 in the presence of positive family history or positive genetic test.
* Core laboratory confirmation of LVEF ≥ 60% AND Valsalva LVOT-G ≥ 50 mmHg.
* oHCM of sarcomeric origin confirmed by genetic testing or, if unable to confirm by genetic testing, oHCM of sarcomeric origin may be presumed in the absence of history of metabolic disorders, mitochondrial cardiomyopathies, neuromuscular disease, malformation syndromes, infiltrative diseases/inflammation, and endocrine disorders (such as Fabry's disease, Noonan syndrome with left ventricular hypertrophy, and amyloid-cardiomyopathy).
* New York Heart Association (NYHA) Class ≥ II at screening.
* Adequate acoustic windows for echocardiography.
* Participants on beta blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for more than 4 weeks prior to randomization.
* Period 2: Open-Label Extension
* Completed Period 1. If unable to complete Period 1 due to circumstances not related to compliance or safety, the Medical Monitor may review and determine eligibility.
* LVEF ≥ 55% after washout
* Period 3: Long-term Extension
* Completed Period 2
Exclusion Criteria:
* Period 1: Treatment Period
Any of the following criteria will exclude potential participants from the trial:
* Significant valvular heart disease.
* Moderate or severe valvular aortic stenosis or fixed subaortic obstruction.
* Mitral regurgitation that is greater than mild in severity and not due to systolic anterior motion of the mitral valve (per judgment of Principal Investigator or designee).
* Evidence of fixed left-sided obstruction (eg, subaortic membrane, aortic valve stenosis, or coarctation of the aorta).
* History of LV systolic dysfunction (LVEF \< 45%) or stress cardiomyopathy at any time during their clinical course.
* History of congenital heart disease other than oHCM (may be enrolled if not hemodynamically significant in the judgement of the Principal Investigator and study Medical Monitor).
* Has been treated with SRT (surgical myectomy or percutaneous alcohol septal ablation) within the preceding 6 months or has plans for either treatment during the trial period.
* History of paroxysmal or persistent atrial fibrillation or atrial flutter.
* History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia within 3 months prior to screening.
* History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the Principal Investigator (or designee) or the Medical Monitor, would pose a risk to participant safety or interfere with the trial evaluation, procedures, or completion.
* Current or previous use of drugs known to cause cardiomyopathy (eg, anthracyclines, monoclonal antibodies \[trastuzumab\], alkylating agents \[cyclophosphamide\], and tyrosine kinase inhibitors \[sunitinib and imatinib\]).
* Currently participating in another investigational device or drug trial or received an investigational device or drug \< 1 month (or 5 half-lives for drugs, whichever is longer) prior to screening.
* Implantable cardioverter defibrillator (ICD) implantation within 6 weeks of screening or planned ICD implantation during the trial period.
* Has received prior treatment with aficamten or mavacamten.
* Currently listed for heart transplantation or anticipated to be listed for heart transplantation in the next 12 months.
Primary outcome measure(s)
Change from baseline in Valsalva left ventricular outflow tract gradient (LVOT-G) — Baseline to week 12 (Period 1)
Trial sites (36)
Facility
City
Region
Status
Phoenix Children's Hospital
Phoenix
Arizona
Arkansas Children's Hospital
Little Rock
Arkansas
Children's Hospital Los Angeles
Los Angeles
California
University of California, Los Angeles (UCLA)
Los Angeles
California
Children's Hospital Colorado
Aurora
Colorado
Children's National Hospital
Washington D.C.
District of Columbia
Nicklaus Children's Hospital
Miami
Florida
Ann & Robert H. Lurie Children's Hospital
Chicago
Illinois
University of Michigan
Ann Arbor
Michigan
Children's Hospital of Michigan
Detroit
Michigan
Mayo Clinic
Rochester
Minnesota
Children's Mercy Hospital
Kansas City
Missouri
University of Nebraska Medical Center
Omaha
Nebraska
Morristown Medical Center
Morristown
New Jersey
NYP/Columbia University Medical Center
New York
New York
Children's Hospital at Montefiore
The Bronx
New York
Duke Clinical Research Institute
Durham
North Carolina
Oregon Health & Science University
Portland
Oregon
Children's Hospital of Philadelphia
Philadelphia
Pennsylvania
LeBonheur Children's Hospital
Memphis
Tennessee
Vanderbilt University Medical Center
Nashville
Tennessee
Dell Children's Hospital
Austin
Texas
UT Southwestern
Dallas
Texas
Children's Wisconsin
Milwaukee
Wisconsin
The Hospital for Sick Children (SickKids)
Toronto
Ontario
Azienda Ospedaliera Universitaria Meyer IRCCS
Florence
Italy
NHO Kagoshima Medical Center
Kagoshima
Japan
University of Osaka Hospital
Osaka
Japan
Kitasato University Hospital
Sagamihara
Japan
National Cerebral and Cardiovascular Center
Suita
Japan
Juntendo University Hospital
Tokyo
Japan
Unidad de Cardiología Infantil; Hospital Universitario da Coruña
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.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.