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

Edgewise Therapeutics

Status and phase: Active, not recruiting; Phase 2

Conditions: Hypertrophic Cardiomyopathy

Treatments: Drug: EDG-7500

Study type: Interventional

Funder types: Industry

Identifiers

NCT06347159

EDG-7500-102

Details and patient eligibility

About

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).

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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100 participants in 4 patient groups

Part A: EDG-7500 Single Dose

Experimental group

Treatment:

Drug: EDG-7500

Drug: EDG-7500

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

Experimental group

Description:

EDG-7500 once daily for up to 28 days.

Treatment:

Drug: EDG-7500

Drug: EDG-7500

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

Experimental group

Description:

EDG-7500 once daily for up to 28 days.

Treatment:

Drug: EDG-7500

Drug: EDG-7500

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

Experimental group

Description:

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

Treatment:

Drug: EDG-7500

Drug: EDG-7500