A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertrophic Cardiomyopathy
• Intervention / Treatment: Drug: EDG-7500; Drug: EDG-7500

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Hospital / Stanford Health Care
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine - Michigan Clinical Research Unit
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center (Atlantic Health System)
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10016
      • NYU Langone Health Medical Center - HCM Program Office (Study open to existing NYU patients only)
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Sanger Heart and Vascular Institute
    • Morrisville, North Carolina, United States, 27560
      • Duke Health Center Arringdon
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center at Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 33612
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Heart and Vascular Center Fontaine
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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).

Key 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.)
• Fridericia-corrected QT interval (QTcF) ≥480 ms or any other ECG abnormality considered by the Investigator or Medical Monitor to pose a risk to participant safety at Screening (QTcF < 530 ms is permitted for participants with documented bundle branch blockage (BBB) and/or cardiac pacing).
• Receiving a CMI (e.g., Camzyos® [mavacamten] or aficamten) < 90 days prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: EDG-7500 Single Dose	Drug: EDG-7500; Liquid suspension formulation of EDG-7500; Drug: EDG-7500; Solid oral formulation of EDG-7500
Experimental: Part B: EDG-7500 Multiple Dose in Adults with Obstructive Hypertrophic Cardiomyopathy; EDG-7500 once daily for up to 28 days.	Drug: EDG-7500; Liquid suspension formulation of EDG-7500; Drug: EDG-7500; Solid oral formulation of EDG-7500
Experimental: Part C: EDG-7500 Multiple Dose in Adults with Nonobstructive Hypertrophic Cardiomyopathy; EDG-7500 once daily for up to 28 days.	Drug: EDG-7500; Liquid suspension formulation of EDG-7500; Drug: EDG-7500; Solid oral formulation of EDG-7500
Experimental: 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.	Drug: EDG-7500; Liquid suspension formulation of EDG-7500; Drug: EDG-7500; Solid oral formulation of EDG-7500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Resting and post-Valsalva LVOT gradient by echocardiography	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)

Collaborators and Investigators

• Sponsor: Edgewise Therapeutics, Inc.
• Investigators: Study Director: Medical Director, Edgewise Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 4, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: EDG-7500-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No