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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2025 by Cytokinetics
Sponsor
Cytokinetics
Information Provided by (Responsible Party)
Cytokinetics
Clinicaltrials.gov Identifier
NCT06412666
Other Study ID Numbers:
CY 6023
First Submitted
May 8, 2024
First Posted
May 13, 2024
Last Update Posted
April 12, 2026
Last Verified
April 2025

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

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.

Condition or DiseaseIntervention/Treatment
PediatricSymptomatic Obstructive Hypertrophic Cardiomyopathy
Drug: AficamtenDrug: Aficamten

Study Design

Study TypeInterventional
Actual Enrollment55 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA 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
Study Start DateMay 28, 2024
Actual Primary Completion Date3yrs 7mos from now
Actual Study Completion Date3yrs 7mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Aficamten
Participants in this arm will receive a single daily oral dose of aficamten with dose levels (5 mg to 20 mg) guided by echocardiography assessments, for 12 weeks during the double-blinded period, for another 52 weeks during the open-label extension period, and for an additional 144 weeks during the long-term extension period.
Drug: Aficamten
Oral Tablet
Placebo
Participants in this arm will receive a single daily oral dose of placebo for 12 weeks during the double-blinded period and then will receive aficamten for 52 weeks during the open-label extension period, followed by an additional 144 weeks of aficamten during the long-term extension period.
Drug: Aficamten
Oral Tablet

Outcome Measures

Primary Outcome Measures
  1. Change from baseline in Valsalva left ventricular outflow tract gradient (LVOT-G)
Secondary Outcome Measures
  1. Change from baseline in resting LVOT-G
  2. Change in values of NT-proBNP
  3. Change in values of hs-cTnI
  4. Change in New York Heart Association (NYHA) Functional Class
  5. Proportion of patients with ≥1 class improvement in NYHA Functional Class
  6. Trough observed plasma concentration (Ctrough) and C2h postdose of aficamten
  7. Maximum observed concentration (Cmax), tmax, AUCtau, and Ctrough of aficamten
    A voluntary intensive PK substudy may occur at Week 8 or Week 12

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsCytokinetics
Locations
Phoenix Children's Hospital | Phoenix Arizona, United States, 85016Children's Hospital Los Angeles | Los Angeles California, United States, 90027University of California, Los Angeles (UCLA) | Los Angeles California, United States, 90095UCSF Benioff Children's Hospital | San Francisco California, United States, 94158Children's Hospital Colorado | Aurora Colorado, United States, 80045Children's National Hospital | Washington D.C. District of Columbia, United States, 20010Nicklaus Children's Hospital | Miami Florida, United States, 33155Ann & Robert H. Lurie Children's Hospital | Chicago Illinois, United States, 60611University of Iowa | Iowa City Iowa, United States, 52242Children's Hospital New Orleans | New Orleans Louisiana, United States, 70018University of Michigan | Ann Arbor Michigan, United States, 48109Children's Hospital of Michigan | Detroit Michigan, United States, 48201Mayo Clinic | Rochester Minnesota, United States, 55905Children's Mercy Hospital | Kansas City Missouri, United States, 64108University of Nebraska Medical Center | Omaha Nebraska, United States, 68198Morristown Medical Center | Morristown New Jersey, United States, 07960NYP/Columbia University Medical Center | New York New York, United States, 10027Children's Hospital at Montefiore | The Bronx New York, United States, 10467Duke Clinical Research Institute | Durham North Carolina, United States, 27701Oregon Health & Science University | Portland Oregon, United States, 97239Children's Hospital of Philadelphia | Philadelphia Pennsylvania, United States, 19104LeBonheur Children's Hospital | Memphis Tennessee, United States, 38103Vanderbilt University Medical Center | Nashville Tennessee, United States, 37235Dell Children's Hospital | Austin Texas, United States, 78723UT Southwestern | Dallas Texas, United States, 75390Children's Wisconsin | Milwaukee Wisconsin, United States, 53226The Hospital for Sick Children (SickKids) | Toronto Ontario, Canada, M5G 1E8Azienda 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 , United Kingdom, SW3 6NPGreat Ormond Street Hospital for Children | London , United Kingdom, WC1N 3BH
Investigators
Study Director: Cytokinetics MD, Cytokinetics