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NCT06412666PHASE2, PHASE3Recruiting

A Study to Evaluate the Effect of Aficamten in Pediatric Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM).

Cytokinetics

Start Date

5/29/2024

Completion Date

1/1/2030

Summary

The purpose of this study is to evaluate the efficacy, safety and PK of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Detailed Description

The overall objective of the trial is to determine the efficacy, safety, and tolerability of administration of aficamten in adolescents (12 to \< 18 years old) and children (6 to \< 12 years old) with symptomatic oHCM. Adolescents and children will be studied in a staged approach involving established favorable pharmacodynamic and safety profiles of aficamten in adolescents followed by further pharmacokinetic modeling to inform the dosing regimen in children. Only the 12 to \<18 years old cohort is currently open for enrollment. The trial will consist of 3 periods: 1. Period 1 is the randomized, double-blind, placebo-controlled treatment period that will assess the efficacy, safety and tolerability of aficamten in pediatric participants. Duration: 12 weeks. 2. Period 2 is the open-label extension trial that will assess the long-term safety of aficamten in pediatric participants, and further assess efficacy and tolerability. Duration: 52 weeks. 3. Period 3 is the long-term extension trial that will assess the long-term safety of aficamten in pediatric participants, and further assess efficacy and tolerability. Duration: 144 weeks.

Eligibility Criteria

Age Range: 12 years to 17 years

Inclusion Criteria: * Period 1: Treatment Period * Males and females between 12 and \< 18 years of age at screening and at Day 1. * Body weight ≥ 45 kg for the initial cohort and then body weight ≥ 35 kg after at least 10 participants in the initial cohort have undergone dose titration up to Week 4 without observed events of LVEF \< 50% at the starting dose of 5 mg qd. * Core laboratory confirmation of the following oHCM echocardiographic criteria at screening: * Left ventricular (LV) hypertrophy with nondilated LV chamber in the absence of other cardiac disease. * 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. * 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.

Interventions

DRUG

Aficamten

DRUG

Placebo

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Conditions

PediatricSymptomatic Obstructive Hypertrophic Cardiomyopathy

Locations

Phoenix Children's Hospital

Phoenix, Arizona 85016

United States

Children's Hospital Los Angeles

Los Angeles, California 90027

United States

University of California, Los Angeles (UCLA)

Los Angeles, California 90095

United States

UCSF Benioff Children's Hospital

San Francisco, California 94158

United States

Children's Hospital Colorado

Aurora, Colorado 80045

United States

Children's National Hospital

Washington D.C., District of Columbia 20010

United States

Nicklaus Children's Hospital

Miami, Florida 33155

United States

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois 60611

United States

University of Iowa

Iowa City, Iowa 52242

United States

Children's Hospital New Orleans

New Orleans, Louisiana 70018

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Children's Hospital of Michigan

Detroit, Michigan 48201

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Children's Mercy Hospital

Kansas City, Missouri 64108

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Morristown Medical Center

Morristown, New Jersey 07960

United States

NYP/Columbia University Medical Center

New York, New York 10027

United States

Children's Hospital at Montefiore

The Bronx, New York 10467

United States

Duke Clinical Research Institute

Durham, North Carolina 27701

United States

Oregon Health & Science University

Portland, Oregon 97239

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

LeBonheur Children's Hospital

Memphis, Tennessee 38103

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37235

United States

Dell Children's Hospital

Austin, Texas 78723

United States

UT Southwestern

Dallas, Texas 75390

United States

Children's Wisconsin

Milwaukee, Wisconsin 53226

United States

The Hospital for Sick Children (SickKids)

Toronto, Ontario M5G 1E8

Canada

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

A Coruña,

Spain

Hospital Sant Joan de Deu

Barcelona,

Spain

Alder Hey Children's Hospital

Liverpool,

United Kingdom

Evelina Children's Hospital

London, SW3 6NP

United Kingdom

Great Ormond Street Hospital for Children

London, WC1N 3BH

United Kingdom