EDG-7500 for Hypertrophic Cardiomyopathy

Recruiting at 20 trial locations

Overseen By Edgewise Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Edgewise Therapeutics, Inc.

Must not be taking: Cardiac myosin inhibitors

Disqualifiers: Coronary artery disease, Atrial fibrillation, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and effects of a new treatment called EDG-7500 for individuals with hypertrophic cardiomyopathy (HCM), a condition where the heart muscle thickens excessively. The study will evaluate different doses, with some participants receiving a single dose and others receiving multiple doses. Individuals diagnosed with HCM who experience symptoms such as chest pain or shortness of breath may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude participants who have used cardiac myosin inhibitors before, so you may need to discuss your current medications with the trial team.

Is there any evidence suggesting that EDG-7500 is likely to be safe for humans?

Research shows that EDG-7500, a new drug for treating hypertrophic cardiomyopathy (HCM), is under testing to assess its safety and effectiveness. Some patients taking EDG-7500 once daily have demonstrated improved heart function. However, certain studies have noted safety concerns, including a decline in heart-related measures that worsens with higher doses, suggesting increased risks at these levels.

EDG-7500 remains under study to fully understand its safety profile. Currently in Phase 2 trials, researchers continue to gather data on patient tolerance. This phase identifies potential side effects and ensures the drug's safety for larger studies. Prospective participants should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypertrophic cardiomyopathy?

Unlike the standard treatments for hypertrophic cardiomyopathy, such as beta-blockers and calcium channel blockers that mainly focus on symptom relief, EDG-7500 offers a novel approach by directly targeting the underlying cardiac muscle abnormalities. Researchers are excited about EDG-7500 because it potentially modifies the disease process itself rather than just managing symptoms. This innovative mechanism could lead to improved heart function and quality of life for patients with both obstructive and nonobstructive forms of the condition.

What evidence suggests that EDG-7500 might be an effective treatment for hypertrophic cardiomyopathy?

This trial will evaluate EDG-7500 for treating hypertrophic cardiomyopathy (HCM), a condition where the heart muscle becomes too thick. Studies have shown that EDG-7500 holds promise for this condition. In a previous study, participants with nonobstructive HCM who took EDG-7500 experienced a 42% average decrease in NT-proBNP levels, a marker indicating heart strain. Research also indicates that EDG-7500 helps the heart muscle relax better. In animal studies, EDG-7500 reduced the blockage in the heart, measured by the left ventricular outflow tract (LVOT) gradient. These results suggest that EDG-7500 could improve heart function in people with HCM. Participants in this trial will receive EDG-7500 in different dosing regimens to further assess its effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Edgewise Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with obstructive hypertrophic cardiomyopathy, a condition where the heart muscle becomes abnormally thick. Participants should not have other serious medical conditions and must be able to follow the study procedures.

Inclusion Criteria

Documented left ventricular ejection fraction (LVEF) ≥0.60 at Screening

LVOT peak gradient ≥30 mmHg measured at rest and ≥50 mmHg post-Valsalva as determined by echocardiography at Screening

Body mass index (BMI) ≥18 to <35 kg/m2; weight ≥50 kg at Screening

Exclusion Criteria

A history of syncope or sustained ventricular tachyarrhythmia <180 days prior to Screening

My heart valve condition is at least Stage B.

I have been diagnosed with atrial fibrillation recently or had treatment for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single dose of EDG-7500

Up to 10 days

Treatment Part B

Participants receive EDG-7500 once daily for up to 28 days

Up to 38 days

Treatment Part C

Participants receive EDG-7500 once daily for up to 28 days

Up to 28 days

Treatment Part D

Participants receive EDG-7500 daily for up to 48 weeks

Up to 49 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EDG-7500

Trial Overview The study tests different doses of EDG-7500, administered either once or multiple times, to see how safe it is and what effects it has on patients with obstructive hypertrophic cardiomyopathy.

How Is the Trial Designed?

Group I: Part D: EDG-7500 Multiple Dose in Adults with Hypertrophic Cardiomyopathy Experimental Treatment 1 Intervention

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

Group II: Part C: EDG-7500 Multiple Dose in Adults with Nonobstructive Hypertrophic Cardiomyopathy Experimental Treatment 1 Intervention

EDG-7500 once daily for up to 28 days.

Group III: Part B: EDG-7500 Multiple Dose in Adults with Obstructive Hypertrophic Cardiomyopathy Experimental Treatment 1 Intervention

EDG-7500 once daily for up to 28 days.

Group IV: Part A: EDG-7500 Single Dose Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Edgewise Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,000+

Published Research Related to This Trial

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, characterized by unexplained thickening of the heart muscle, which can lead to serious complications like heart failure and arrhythmias.

Recent advancements in pharmacological treatments specifically targeting HCM's underlying mechanisms have shown promising results in improving patients' functional capacity and symptoms, indicating a shift towards more effective management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stage-specific therapy for hypertrophic cardiomyopathy. Argirò, A., Zampieri, M., Marchi, A., et al.[2023]

Hypertrophic cardiomyopathy (HCM) is primarily caused by mutations in sarcomere genes, leading to altered heart cell function and a range of symptoms, including heart failure and sudden cardiac death, making early identification and management crucial.

Current management strategies focus on preventing sudden death through risk stratification, genetic diagnosis, and timely interventions, which have significantly reduced mortality rates in the last decade, although no causal therapy exists for this inherited condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertrophic cardiomyopathy: genetics and clinical perspectives. Wolf, CM.[2020]

Myosin inhibitors have emerged as a promising new treatment for obstructive hypertrophic cardiomyopathy, showing effectiveness in relieving symptoms and improving patients' quality of life based on recent clinical trials.

Current treatment options for left ventricular outflow tract obstruction include both pharmacological therapies and surgical interventions, highlighting the need for a comprehensive approach to manage this common genetic condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic approaches in hypertrophic cardiomyopathy: from symptom relief to precision therapy]. Argirò, A., Zampieri, M., Marchi, A., et al.[2023]

Hypertrophic cardiomyopathy is a genetic condition that can lead to serious heart issues, including sudden cardiac death, making it crucial to identify high-risk patients based on clinical factors like age, syncope, and family history.

The implantable cardioverter-defibrillator (ICD) is an effective treatment for reducing the risk of sudden cardiac death in high-risk patients with hypertrophic cardiomyopathy, replacing amiodarone as the preferred prophylactic measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sudden death and hypertrophic cardiomyopathy: a review. Ly, HQ., Greiss, I., Talakic, M., et al.[2013]

Hypertrophic cardiomyopathy affects about 0.2% of the population and can lead to serious symptoms like angina and heart failure; effective diagnosis involves ECG, echocardiography, and cardiac MRI for risk assessment.

Treatment options include beta-blockers for symptom management, and for patients with significant outflow tract obstruction, surgical myectomy or catheter-based septum ablation can provide significant relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnosis and treatment of hypertrophic cardiomyopathies]. Kühl, C., Luedde, M., Langer, C., et al.[2013]

Citations

1. prnewswire.com prnewswire.com/news-releases/edgewise-therapeutics-announces-positive-top-line-results-from-phase-2-cirrus-hcm-four-week-trial-of-edg-7500-in-hypertrophic-cardiomyopathy-hcm-302417857.html

Edgewise Therapeutics Announces Positive Top-Line ... In participants with nonobstructive HCM, EDG-7500 administration resulted in a dose-dependent reduction in NT-proBNP, with a 42% mean decrease ...

2. emjreviews.com emjreviews.com/cardiology/article/novel-cardiac-sarcomere-modulator-edg-7500-in-hypertrophic-cardiomyopathy-evaluating-new-phase-ii-data-from-cirrus-hcm/

Novel Cardiac Sarcomere Modulator, EDG-7500, in ... Edgewise Therapeutics announces positive top-line results from Phase 2 CIRRUS-HCM four-week trial of EDG-7500 in hypertrophic cardiomyopathy ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06347159

A Study of EDG-7500 in Adults With Hypertrophic ... 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 ...

4. edgewisetx.com edgewisetx.com/science-pipeline/edg-7500/

Cardiac Diastolic Dysfunction - EDG-7500 EDG-7500 is a novel oral, selective cardiac sarcomere modulator for the treatment of HCM and other serious diseases of cardiac diastolic dysfunction.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1071916424008418

EDG-7500, A First-in-Class Cardiac Sarcomere Modulator ... In a cat model of obstructive HCM (oHCM), the IC50 of EDG-7500 was 125 ng/mL for a 50% reduction in left ventricular outflow tract (LVOT) gradient.

6. s204.q4cdn.com s204.q4cdn.com/663829792/files/doc_events/2025/Apr/02/EDG-7500-CIRRUS-Parts-B-and-C-Disclosure_vFINAL.pdf

EDG-7500: Phase 2 CIRRUS-HCM Development Program ... 2020;396(10253):759-769. LIMITED BENEFIT ACROSS. THE SPECTRUM OF HCM. SAFETY RISKS WORSEN. PATIENT EXPERIENCE. RISK OF HEART FAILURE1,2.

7. firstwordpharma.com firstwordpharma.com/story/5946913

Safety signals overshadow Edgewise's HCM drug trial results As for the latest CIRRUS-HCM data, the company said that in participants with obstructive HCM, once-daily EDG-7500 led to a dose-dependent drop ...