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

Purpose

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).

Condition

  • Hypertrophic Cardiomyopathy

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.) - 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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A: EDG-7500 Single Dose
  • Drug: EDG-7500
    Liquid suspension 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
    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
    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
    Solid oral formulation of EDG-7500

Recruiting Locations

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Contact:
Albree Tower-Rader, MD
617-643-0122

More Details

Status
Recruiting
Sponsor
Edgewise Therapeutics, Inc.

Study Contact

Edgewise Therapeutics, Inc.
720-262-7002
cardiacstudies@edgewisetx.com