## Protocol Section
### Identification Module
**NCT ID:** NCT06412666

**Acronym:** CEDAR-HCM

**Brief Title:** A Study to Evaluate the Effect of Aficamten in Pediatric Patients (Age 12 to <18 Years) With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM).

**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

#### Organization Study ID Info
**ID:** CY 6023
#### Organization
**Class:** INDUSTRY
**Full Name:** Cytokinetics
#### Secondary ID Infos
**ID:** 2024-511377-30-00
**Type:** CTIS
### Status Module
#### Completion Date
**Date:** 2028-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2028-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Cytokinetics

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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).

**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 trial will consist of 2 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: approximately 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: approximately 52 weeks.

### Conditions Module

**Conditions:**

- Pediatric

- Symptomatic Obstructive Hypertrophic Cardiomyopathy

**Keywords:**

- CK-3773274

- CK-274

- Aficamten

- Symptomatic Obstructive Hypertrophic Cardiomyopathy

- oHCM

- CEDAR

- CEDAR-HCM

- CY 6023

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- PHASE2

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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, and then for another 52 weeks during the open-label extension period.

**Intervention Names:**

- Drug: Aficamten

**Label:** Aficamten

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants in this arm will receive placebo for 12 weeks during the double-blinded period, and then will receive aficamten for 52 weeks during the open-label extension period.

**Intervention Names:**

- Drug: Aficamten

- Drug: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Aficamten

- Placebo

**Description:** Oral Tablet

**Name:** Aficamten

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Oral Tablet

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Change from baseline in Valsalva left ventricular outflow tract gradient (LVOT-G)

**Time Frame:** Baseline to week 12

#### Secondary Outcomes

**Measure:** Change from baseline in resting LVOT-G

**Time Frame:** Baseline to week 12

**Measure:** Change in values of NT-proBNP

**Time Frame:** Baseline to week 12

**Measure:** Change in values of hs-cTnI

**Time Frame:** Baseline to week 12

**Measure:** Change in New York Heart Association (NYHA) Functional Class

**Time Frame:** Baseline to week 12

**Measure:** Proportion of patients with ≥1 class improvement in NYHA Functional Class

**Time Frame:** Baseline to week 12

**Measure:** Trough observed plasma concentration (Ctrough) of aficamten

**Time Frame:** Baseline to week 12

**Description:** A voluntary intensive PK substudy may occur at Week 8 or Week 12

**Measure:** Maximum observed concentration (Cmax) of aficamten

**Time Frame:** Week 8 or Week 12

### Eligibility Module

**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 symptoms or 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.

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).
  * No evidence of fixed left-sided obstruction (eg, subaortic, aortic valve, 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) 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.

Period 2:

Exclusion Criteria:

Had a confirmed LVEF \< 40% with an associated dose interruption during participation in Period 1.

**Maximum Age:** 17 Years

**Minimum Age:** 12 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** medicalaffairs@cytokinetics.com

**Name:** Cytokinetics MD

**Phone:** 6506242929

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Cytokinetics

**Name:** Cytokinetics MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000020763

- Term: Pathological Conditions, Anatomical

- ID: D000001020

- Term: Aortic Stenosis, Subvalvular

- ID: D000001024

- Term: Aortic Valve Stenosis

- ID: D000082862

- Term: Aortic Valve Disease

- ID: D000006349

- Term: Heart Valve Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10035

- Name: Hypertrophy

- Relevance: HIGH

- As Found: Hypertrophic

- ID: M12154

- Name: Cardiomyopathies

- Relevance: HIGH

- As Found: Cardiomyopathy

- ID: M5568

- Name: Cardiomyopathy, Hypertrophic

- Relevance: HIGH

- As Found: Hypertrophic Cardiomyopathy

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: M6475

- Name: Constriction, Pathologic

- Relevance: LOW

- As Found: Unknown

- ID: M4340

- Name: Aortic Valve Stenosis

- Relevance: LOW

- As Found: Unknown

- ID: M2379

- Name: Aortic Valve Disease

- Relevance: LOW

- As Found: Unknown

- ID: M9437

- Name: Heart Valve Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T449

- Name: Aortic Valve Stenosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009202

- Term: Cardiomyopathies

- ID: D000002312

- Term: Cardiomyopathy, Hypertrophic

- ID: D000006984

- Term: Hypertrophy

### Misc Info Module

- Version Holder: 2024-05-31
