PediatricPhase 2/3CEDAR-HCMNCT06412666
A Study to Evaluate the Effect of Aficamten in Pediatric Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM).
A Phase 2/3 study testing Aficamten in people with Pediatric and Symptomatic Obstructive Hypertrophic Cardiomyopathy, run by Cytokinetics at 36 sites in 6 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Pediatric, Symptomatic Obstructive Hypertrophic Cardiomyopathy
- What is being tested?
- Aficamten
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 36 sitesin 6 countries
- Study dates
- 29 May 2024to Jan 2030
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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:
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- 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
Who cannot join
- 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).
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- 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.
Trial locations and contacts
36 sites in 6 countries.
36 sites in 6 countries
United States24 sites
University of Michigan
Ann Arbor, Michigan, 48109
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Hospital
Austin, Texas, 78723
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
UT Southwestern
Dallas, Texas, 75390
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke Clinical Research Institute
Durham, North Carolina, 27701
Children's Mercy Hospital
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of California, Los Angeles (UCLA)
Los Angeles, California, 90095
LeBonheur Children's Hospital
Memphis, Tennessee, 38103
Nicklaus Children's Hospital
Miami, Florida, 33155
Children's Wisconsin
Milwaukee, Wisconsin, 53226
Morristown Medical Center
Morristown, New Jersey, 07960
Vanderbilt University Medical Center
Nashville, Tennessee, 37235
NYP/Columbia University Medical Center
New York, New York, 10027
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
Children's Hospital at Montefiore
The Bronx, New York, 10467
Children's National Hospital
Washington D.C., District of Columbia, 20010
Japan5 sites
NHO Kagoshima Medical Center
Kagoshima
University of Osaka Hospital
Osaka
Kitasato University Hospital
Sagamihara
National Cerebral and Cardiovascular Center
Suita
Juntendo University Hospital
Tokyo
United Kingdom3 sites
Alder Hey Children's Hospital
Liverpool
Evelina Children's Hospital
London, SW3 6NP
Great Ormond Street Hospital for Children
London, WC1N 3BH
Spain2 sites
Unidad de Cardiología Infantil; Hospital Universitario da Coruña
A Coruña
Hospital Sant Joan de Deu
Barcelona
Canada1 site
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G 1E8
About this study
Official title: 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).
Read the 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:
- Period 1 is the randomized, double-blind, placebo-controlled treatment period that will assess the efficacy, safety and tolerability of aficamten in pediatric participants.
- 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.
- 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.
- Being tested
- Aficamten, Placebo
- Keywords
- CK-3773274, CK-274, Aficamten, Symptomatic Obstructive Hypertrophic Cardiomyopathy, oHCM, CEDAR, CEDAR-HCM, CY 6023
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AficamtenDrug
Oral Tablet
PlaceboDrug
Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| Aficamten | Experimental | 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. Receives: Drug: Aficamten |
| Placebo | Placebo comparator | 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. Receives: Drug: Aficamten; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Valsalva left ventricular outflow tract gradient (LVOT-G)
Measured: Baseline to week 12 (Period 1)
Secondary outcomes (16)
Change from baseline in resting LVOT-G
Measured: Baseline to week 12 (Period 1)
Trough observed plasma concentration (Ctrough) and concentration 2 hours postdose of aficamten
Measured: Baseline to week 12 (Period 1)
Change in values of N-terminal prohormone brain natriuretic peptide (NT-proBNP)
Measured: Baseline to week 12 (Period 1)
Change in values of high sensitivity cardiac troponin I (hs-cTnI)
Measured: Baseline to week 12 (Period 1)
Change in New York Heart Association (NYHA) Functional Class
Measured: 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
Measured: 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
Measured: 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
Measured: Up to week 210
Number of participants with appropriate implantable cardioverter defibrillator (ICD) discharges
Measured: Up to week 210
Number of participants with left ventricular ejection fraction (LVEF) < 50%
Measured: 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
Measured: Up to week 210
Proportion of participants with Valsalva LVOT-G < 50 mmHg
Measured: Week 14 to week 66 (Period 2), and up to week 210 (Period 3)
Proportion of participants with Valsalva LVOT-G < 30 mmHg
Measured: 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
Measured: 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
Measured: Time to event through last follow-up, up to week 210
Time to first valsalva LVOT-G < 30 mmHg through last follow-up
Measured: Time to event through last follow-up, up to week 210
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2024
- Study start29 May 2024
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PediatricStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Cytokinetics MD, Study director, Cytokinetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06412666
- Sponsor's protocol ID
- CY 6023
- Other IDs
- 2024-511377-30-00
- Acronym
- CEDAR-HCM
- Status last verified
- Aug 2026
- First submitted
- 9 May 2024
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 41347307