Hypertrophic Cardiomyopathy
Conditions
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).
Interventions
DRUGEDG-7500
Liquid suspension formulation of EDG-7500
Sponsors
Edgewise Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Resting and post-Valsalva LVOT gradient by echocardiography |
| Pharmacokinetic parameters of EDG-7500 as measured by maximum plasma concentration (Cmax) | From baseline through study completion (Part A: Up to 10 days) | — |
| 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) | — |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Edgewise Therapeutics, Inc.
Outcome results
None listed