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

Last updated: May 2, 2025
Sponsor: Cytokinetics
Overall Status: Active - Recruiting

Phase

2/3

Condition

Circulation Disorders

Treatment

Placebo

Aficamten

Clinical Study ID

NCT06412666
CY 6023
2024-511377-30-00
  • Ages 12-17
  • All Genders

Study 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 Criteria

Inclusion

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 afterat least 10 participants in the initial cohort have undergone dose titration upto Week 4 without observed events of LVEF < 50% at the starting dose of 5 mgqd.

  • Core laboratory confirmation of the following oHCM echocardiographic criteriaat screening:

  • Left ventricular (LV) hypertrophy with nondilated LV chamber in the absence of othercardiac 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 genetictest.

  • LVEF ≥ 60% AND Valsalva LVOT-G ≥ 50 mmHg.

  • oHCM of sarcomeric origin confirmed by genetic testing or, if unable to confirmby genetic testing, oHCM of sarcomeric origin may be presumed in the absence ofhistory of metabolic disorders, mitochondrial cardiomyopathies, neuromusculardisease, malformation syndromes, infiltrative diseases/inflammation, andendocrine disorders (such as Fabry's disease, Noonan syndrome with leftventricular 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 shouldhave 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 relatedto compliance or safety, the Medical Monitor may review and determine eligibility.

  • LVEF ≥ 55% after washout.

Exclusion

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 tosystolic anterior motion of the mitral valve (per judgment of PrincipalInvestigator or designee).

  • Evidence of fixed left-sided obstruction (eg, subaortic membrane, aortic valvestenosis, or coarctation of the aorta).

  • History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy at any timeduring their clinical course.

  • History of congenital heart disease other than oHCM (may be enrolled if nothemodynamically significant in the judgement of the Principal Investigator and studyMedical Monitor).

  • Has been treated with SRT (surgical myectomy or percutaneous alcohol septalablation) within the preceding 6 months or has plans for either treatment during thetrial period.

  • History of paroxysmal or persistent atrial fibrillation or atrial flutter.

  • History of syncope, symptomatic ventricular arrhythmia, or sustained ventriculartachyarrhythmia within 3 months prior to screening.

  • History or evidence of any other clinically significant disorder, malignancy, activeinfection, other condition, or disease that, in the opinion of the PrincipalInvestigator (or designee) or the Medical Monitor, would pose a risk to participantsafety 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], andtyrosine kinase inhibitors [sunitinib and imatinib]).

  • Currently participating in another investigational device or drug trial or receivedan investigational device or drug < 1 month (or 5 half-lives for drugs, whichever islonger) prior to screening.

  • Implantable cardioverter defibrillator (ICD) implantation within 6 weeks ofscreening 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 hearttransplantation in the next 12 months.

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 2/3
Study Start date:
May 29, 2024
Estimated Completion Date:
January 31, 2030

Study 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.

Connect with a study center

  • The Hospital for Sick Children (SickKids)

    Toronto, Ontario M5G 1E8
    Canada

    Site Not Available

  • Careggi University Hospital

    Florence,
    Italy

    Active - Recruiting

  • Unidad de Cardiología Infantil; Hospital Universitario da Coruña

    A Coruña,
    Spain

    Active - Recruiting

  • Alder Hey Children's Hospital

    Liverpool,
    United Kingdom

    Active - Recruiting

  • Great Ormond Street Hospital for Children

    London, WC1N 3BH
    United Kingdom

    Active - Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California 90027
    United States

    Site Not Available

  • University of California, Los Angeles (UCLA)

    Los Angeles, California 90095
    United States

    Active - Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado 80045
    United States

    Active - Recruiting

  • Children's National Hospital

    Washington, District of Columbia 20010
    United States

    Active - Recruiting

  • Baptist Health South Florida

    Miami, Florida 33176
    United States

    Site Not Available

  • Ann & Robert H. Lurie Children's Hospital

    Chicago, Illinois 60611
    United States

    Site Not Available

  • University of Iowa

    Iowa City, Iowa 52242
    United States

    Active - Recruiting

  • Children's Hospital New Orleans

    New Orleans, Louisiana 70018
    United States

    Site Not Available

  • University of Michigan

    Ann Arbor, Michigan 48109
    United States

    Active - Recruiting

  • Children's Hospital of Michigan

    Detroit, Michigan 48201
    United States

    Active - Recruiting

  • Mayo Clinic

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

  • Children's Mercy Hospital

    Kansas City, Missouri 64108
    United States

    Active - Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198
    United States

    Site Not Available

  • Morristown Medical Center

    Morristown, New Jersey 07960
    United States

    Active - Recruiting

  • Columbia University

    New York, New York 10027
    United States

    Site Not Available

  • NYP/Columbia University Medical Center

    New York, New York 10027
    United States

    Site Not Available

  • Duke Clinical Research Institute

    Durham, North Carolina 27701
    United States

    Site Not Available

  • Oregon Health & Science University

    Portland, Oregon 97239
    United States

    Active - Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • LeBonheur Children's Hospital

    Memphis, Tennessee 38103
    United States

    Site Not Available

  • Vanderbilt University Medical Center

    Nashville, Tennessee 37235
    United States

    Active - Recruiting

  • UT Southwestern

    Dallas, Texas 75390
    United States

    Site Not Available

  • Children's Wisconsin

    Milwaukee, Wisconsin 53226
    United States

    Site Not Available

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