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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Pediatric; Symptomatic Obstructive Hypertrophic Cardiomyopathy
• Intervention / Treatment: Drug: Placebo; Drug: Aficamten

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.

The 12 to <18 years old cohort has enrolled all participants and is no longer recruiting, the 6 to < 12 year old cohort is not yet recruiting.

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.
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.
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.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1E8
      • The Hospital for Sick Children (SickKids)
• Italy
  • Florence, Italy
    • Azienda Ospedaliera Universitaria Meyer IRCCS
• Japan
  • Kagoshima, Japan
    • NHO Kagoshima Medical Center
  • Osaka, Japan
    • University of Osaka Hospital
  • Sagamihara, Japan
    • Kitasato University Hospital
  • Suita, Japan
    • National cerebral and cardiovascular center
  • Tokyo, Japan
    • Juntendo University Hospital
• Spain
  • A Coruña, Spain
    • Unidad de Cardiología Infantil; Hospital Universitario da Coruña
  • Barcelona, Spain
    • Hospital Sant Joan De Deu
• United Kingdom
  • Liverpool, United Kingdom
    • Alder Hey Children's Hospital
  • London, United Kingdom, SW3 6NP
    • Evelina Children's Hospital
  • London, United Kingdom, WC1N 3BH
    • Great Ormond Street Hospital for Children
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles (UCLA)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • New York, New York, United States, 10027
      • NYP/Columbia University Medical Center
    • The Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Duke Clinical Research Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • LeBonheur Children's Hospital
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 Comparator: 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: Placebo; Oral Tablet; Drug: Aficamten; Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Valsalva left ventricular outflow tract gradient (LVOT-G)	Baseline to week 12 (Period 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in resting LVOT-G		Baseline to week 12 (Period 1)
Trough observed plasma concentration (Ctrough) and concentration 2 hours postdose of aficamten		Baseline to week 12 (Period 1)
Change in values of N-terminal prohormone brain natriuretic peptide (NT-proBNP)		Baseline to week 12 (Period 1)
Change in values of high sensitivity cardiac troponin I (hs-cTnI)		Baseline to week 12 (Period 1)
Change in New York Heart Association (NYHA) Functional Class		Baseline to week 12 (Period 1), week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Change in peak LVOT-G	Change in peak LVOT-G at rest and with valsalva provocation will be assessed at 12 week intervals during Period 2 and 24 week intervals during Period 3	Week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Proportion of participants with ≥1 class improvement in NYHA Functional Class		Baseline to week 12 (Period 1), week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Number of participants that have drug interruption or early discontinuation		Up to week 210
Number of participants with appropriate implantable cardioverter defibrillator (ICD) discharges		Up to week 210
Number of participants with left ventricular ejection fraction (LVEF) < 50%		Baseline to week 12 (Period 1), week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Number of participants with clinically significant changes in vital signs, 12-lead electrocardiogram (ECGs) and safety laboratory parameters		Up to week 210
Proportion of participants with Valsalva LVOT-G < 50 mmHg		Week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Proportion of participants with Valsalva LVOT-G < 30 mmHg		Week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Time to first resting LVOT-G < 30 mmHg through last follow-up		Time to the following event through last follow-up, up to week 210
Time to first valsalva LVOT-G < 50 mmHg through last follow-up		Time to event through last follow-up, up to week 210
Time to first valsalva LVOT-G < 30 mmHg through last follow-up		Time to event through last follow-up, up to week 210

Collaborators and Investigators

• Sponsor: Cytokinetics
• Collaborators: Bayer
• Investigators: Study Director: Cytokinetics MD, Cytokinetics

Publications and helpful links

General Publications

• Kaski JP, Kantor PF, Nakano SJ, Olivotto I, Russell MW, Godown J, Chiu M, German P, Heitner SB, Jacoby DL, Kupfer S, Lutz J, Maharao N, Malik FI, Melloni C, Nieto Morales PF, Simkins T, Wei J, Ho CY; CEDAR-HCM Investigators. Efficacy and Safety of Aficamten in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy: Study Design and Rationale of CEDAR-HCM. Circ Heart Fail. 2026 Feb;19(2):e013418. doi: 10.1161/CIRCHEARTFAILURE.125.013418. Epub 2025 Dec 5.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): August 18, 2026
• Last Update Submitted That Met QC Criteria: August 14, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: oHCM; CK-3773274; CK-274; Aficamten; Symptomatic Obstructive Hypertrophic Cardiomyopathy; CEDAR; CEDAR-HCM; CY 6023
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: CY 6023; 2024-511377-30-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No