Clinical trial NCT06347159: A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM)
Official title: An Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of EDG-7500 in Adults With Hypertrophic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypertrophic Cardiomyopathy
Lead sponsor: Edgewise Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-04
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is being conducted in order to understand the safety and effects of different doses of EDG-7500 as a single dose in adults with obstructive hypertrophic cardiomyopathy (oHCM) and as multiple doses in adults with obstructive or nonobstructive hypertrophic cardiomyopathy (nHCM).


Eligibility criteria: Key Inclusion Criteria:

* Male or nonpregnant female, age ≥18 years.
* Body mass index (BMI) ≥18 to \<38 kg/m2; weight ≥50 kg at Screening.
* Diagnosed with hypertrophic cardiomyopathy at the time of Screening consistent with current American College of Cardiology Foundation/American Heart Association Guidelines
* LVOT peak gradient ≥30 mmHg measured at rest and ≥50 mmHg post-Valsalva as determined by echocardiography at Screening (Part A, B and D oHCM only).
* LVOT peak gradient \< 30 mmHg measured at rest and \< 50 mmHg measured during the Valsalva maneuver as determined by echocardiography as assessed by the Investigator at Screening (Part C and D nHCM only).
* Maximal exercise peak LVOT gradient \< 50 mmHg as determined by echocardiography as assessed by the Investigator (historical documentation \< 12 months prior to dosing or confirmed at Screening) (Part C and D nHCM only).
* Documented left ventricular ejection fraction (LVEF) ≥0.60 at Screening.
* New York Heart Association (NYHA) Classification I-III at Screening.

Key Exclusion Criteria:

* Invasive septal reduction \<180 days prior to Screening.
* Documented current or history of obstructive coronary artery disease at any time or myocardial infarction \<180 days prior to Screening.
* Known Stage B or higher aortic valve stenosis or regurgitation
* Documented current or history of cardiac amyloidosis (age ≥ 60 years requires exclusion of cardiac amyloidosis by radionuclide scan or MRI performed at Screening or historical scan \<3 years prior to Screening).
* A history of syncope or sustained ventricular tachyarrhythmia \<180 days prior to Screening.
* A history of sudden cardiac arrest at any time or known appropriate implantable cardioverter defibrillator (ICD) discharge \<180 days prior to Screening
* Atrial fibrillation (AF) at Screening; a current diagnosis of permanent AF; paroxysmal or persistent AF \<90 days of Screening, or electrical cardioversion or ablation for AF \<90 days of Screening.
* Fridericia-corrected QT interval (QTcF) ≥480 ms or any other ECG abnormality considered by the Investigator to pose a risk to participant safety.
* Current or prior use of any cardiac myosin inhibitors
* A history of diabetes with a hemoglobin A1C ≥ 7.5% at the Screening Visit (Part C and D nHCM only)

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: From screening through study completion (Part A: Up to 38 days; Part B and C: Up to 66 days; Part D: Up to 53 weeks)
Secondary outcomes:
measure: Change from baseline in left ventricular outflow tract (LVOT) gradient
timeFrame: From baseline through study completion (Part A: Up to 10 days; Part B: Up to 38 days; Part D: Up to 49 weeks)
measure: Pharmacokinetic parameters of EDG-7500 as measured by maximum plasma concentration (Cmax)
timeFrame: From baseline through study completion (Part A: Up to 10 days; Part B and C: Up to 38 days)
measure: Change from baseline in cardiac biomarkers
timeFrame: From baseline through study completion (Part B and C: Up to 38 days; Part D: Up to 49 weeks)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Hospital / Stanford Health Care
state: California
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Morristown
country: United States
facility: Morristown Medical Center (Atlantic Health System)
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health Medical Center - HCM Program Office
state: New York
city: Cincinnati
country: United States
facility: The Lindner Research Center at Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)
state: Pennsylvania
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Edgewise Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: