Brief 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).
Brief Title
A Study to Evaluate the Effect of Aficamten in Pediatric Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM).
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. 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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
6506242929
Central Contact Email
medicalaffairs@cytokinetics.com
Completion Date
Completion Date Type
Estimated
Conditions
Pediatric
Symptomatic Obstructive Hypertrophic Cardiomyopathy
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
CK-3773274
CK-274
Aficamten
Symptomatic Obstructive Hypertrophic Cardiomyopathy
oHCM
CEDAR
CEDAR-HCM
CY 6023
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
12 Years
NCT Id
NCT06412666
Org Class
Industry
Org Full Name
Cytokinetics
Org Study Id
CY 6023
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Measure
Change from baseline in Valsalva left ventricular outflow tract gradient (LVOT-G)
Outcome Time Frame
Baseline to week 12
Secondary Ids
Secondary Id
2024-511377-30-00
Secondary Outcomes
Outcome Time Frame
Baseline to week 12
Outcome Measure
Change from baseline in resting LVOT-G
Outcome Time Frame
Baseline to week 12
Outcome Measure
Change in values of NT-proBNP
Outcome Time Frame
Baseline to week 12
Outcome Measure
Change in values of hs-cTnI
Outcome Time Frame
Baseline to week 12
Outcome Measure
Change in New York Heart Association (NYHA) Functional Class
Outcome Time Frame
Baseline to week 12
Outcome Measure
Proportion of patients with ≥1 class improvement in NYHA Functional Class
Outcome Time Frame
Baseline to week 12
Outcome Measure
Trough observed plasma concentration (Ctrough) and C2h postdose of aficamten
Outcome Description
A voluntary intensive PK substudy may occur at Week 8 or Week 12
Outcome Time Frame
Week 8 or Week 12
Outcome Measure
Maximum observed concentration (Cmax), tmax, AUCtau, and Ctrough of aficamten
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Daphne Hsu
Investigator Email
dhsu@montefiore.org
Investigator Phone
718-741-2538
Investigator Department
Pediatrics
Investigator Division
Pediatric Cardiology
Investigator Sponsor Organization
External
Study Department
Pediatrics
Study Division
Pediatrics Cardiology