An Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of EDG-7500 in Adults With Hypertrophic Cardiomyopathy

Edgewise Therapeutics, Inc.28 sites in 1 country100 target enrollmentApril 11, 2024

ConditionsHypertrophic Cardiomyopathy

InterventionsEDG-7500

DrugsEDG-7500

Overview

Phase: Phase 2
Intervention: EDG-7500
Conditions: Hypertrophic Cardiomyopathy
Sponsor: Edgewise Therapeutics, Inc.
Enrollment: 100
Locations: 28
Primary Endpoint: Incidence of treatment-emergent adverse events
Status: Active, not recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

April 11, 2024

End Date

December 1, 2026

Last Updated

2 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Edgewise Therapeutics, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or nonpregnant female, age ≥18 years to \<85 years.
•Body mass index (BMI) ≥18 to \<35 kg/m2; weight ≥50 kg at Screening (BMI ≥ 18 to \< 40 kg/m2 is permitted for participants \< 50 years).
•Diagnosed with hypertrophic cardiomyopathy at the time of Screening consistent with current American College of Cardiology Foundation/American Heart Association Guidelines.
•LVOT peak gradient ≥ 50 mmHg measured at rest or during the Valsalva maneuver 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 at Screening (Part C and D nHCM only).
•Documented left ventricular ejection fraction (LVEF) ≥ 0.60 at Screening.
•New York Heart Association (NYHA) Classification II-III at Screening.
•Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) \< 85 at Screening.
•NT-proBNP ≥ 300 pg/mL (NT-proBNP ≥ 225 pg/mL is permitted for African American participants) (Part C and D nHCM only).

Exclusion Criteria

•Invasive septal reduction therapy \< 180 days prior to or during Screening.
•Documented history of active or untreated obstructive coronary artery disease during Screening or treated for obstructive coronary artery disease \< 180 days prior to Screening.
•Documented history of myocardial infarction with residual wall motion abnormalities \< 180 days prior to or during Screening.
•Significant valvular heart disease (moderate or greater aortic stenosis or regurgitation, moderate or greater mitral stenosis or regurgitation not due to systolic anterior motion of the mitral valve)
•History of LV systolic dysfunction (LVEF \< 0.45) or stress cardiomyopathy at any time.
•Known or suspected infiltrative or storage disorder causing cardiac hypertrophy that may mimic HCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
•A history of unexplained syncope \<180 days prior to or during Screening.
•A history of sustained ventricular tachyarrhythmia or sudden cardiac arrest \< 180 days prior or during Screening.
•A history of known appropriate implantable cardioverter defibrillator (ICD) discharge \<180 days prior to or during Screening or ICD implanted \< 14 days prior to Screening.
•History of permanent AF or atrial flutter. Documented AF or atrial flutter requiring rhythm restoring treatment \< 180 days prior to Screening Visit (participants with documented AF or atrial flutter requiring rhythm restoring treatment ≥ 180 days prior to Screening require adequate anticoagulation.)

Arms & Interventions

Part A: EDG-7500 Single Dose

Intervention: EDG-7500

Part B: EDG-7500 Multiple Dose in Adults with Obstructive Hypertrophic Cardiomyopathy

EDG-7500 once daily for up to 28 days.

Intervention: EDG-7500

Part C: EDG-7500 Multiple Dose in Adults with Nonobstructive Hypertrophic Cardiomyopathy

EDG-7500 once daily for up to 28 days.

Intervention: EDG-7500

Part D: EDG-7500 Multiple Dose in Adults with Hypertrophic Cardiomyopathy

EDG-7500 daily for up to 18 months in new participants and participants who have completed Part B or C.

Intervention: EDG-7500

Outcomes

Primary Outcomes

Incidence of treatment-emergent adverse events

Time Frame: From screening through study completion (Part A: Up to 38 days; Part B and C: Up to 73 days; Part D: Up to 18 months)

Secondary Outcomes

Change from baseline in cardiac biomarkers(From baseline through study completion (Part B and C: Up to 38 days; Part D: Up to 18 months))
Change from baseline in left ventricular outflow tract (LVOT) gradient(From baseline through study completion (Part A: Up to 10 days; Part B: Up to 38 days; Part D: Up to 18 months))
Pharmacokinetic parameters of EDG-7500 as measured by maximum plasma concentration (Cmax)(From baseline through study completion (Part A: Up to 10 days))