RecruitingPhase 2Phase 3NCT06412666

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

A Phase 2/3 Multicenter, Randomized, Double-Blind, Placebo-Controlled and Open-Label Extension Trial to Evaluate the Efficacy and Safety of Aficamten in a Pediatric Population With Symptomatic Obstructive Hypertrophic Cardiomyopathy


Sponsor

Cytokinetics

Enrollment

55 participants

Start Date

May 29, 2024

Study Type

INTERVENTIONAL

Conditions

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).


Eligibility

Min Age: 12 YearsMax Age: 17 Years

Inclusion Criteria17

  • 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 Criteria17

  • 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.

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Interventions

DRUGAficamten

Oral Tablet

DRUGPlacebo

Oral Tablet


Locations(38)

Phoenix Children's Hospital

Phoenix, Arizona, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Hospital

Washington D.C., District of Columbia, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

Children's Hospital New Orleans

New Orleans, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Morristown Medical Center

Morristown, New Jersey, United States

NYP/Columbia University Medical Center

New York, New York, United States

Children's Hospital at Montefiore

The Bronx, New York, United States

Duke Clinical Research Institute

Durham, North Carolina, United States

Oregon Health & Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

LeBonheur Children's Hospital

Memphis, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Dell Children's Hospital

Austin, Texas, United States

UT Southwestern

Dallas, Texas, United States

Children's Wisconsin

Milwaukee, Wisconsin, United States

The Hospital for Sick Children (SickKids)

Toronto, Ontario, Canada

Careggi University Hospital

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, United Kingdom

Great Ormond Street Hospital for Children

London, United Kingdom

View Full Details on ClinicalTrials.gov

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NCT06412666


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