A Phase 2 Study of CRD-4730 in CPVT (CPVT)

A Phase 2, Double-Blind, Repeat-Dose, Placebo-Controlled Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CRD-4730 In Participants With Catecholaminergic Polymorphic Ventricular Tachycardia

This is a Phase 2, multicenter, double-blind, sponsor blinded, placebo-controlled, repeat-dose clinical study of CRD-4730 to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CRD-4730 to participants with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Participants with CPVT will complete a 3-period, randomized 3-sequence study. Each participant will be randomized to one of the 3 sequences in which they will receive 2 different doses of CRD-4730 and 1 dose of matching placebo.

Study Overview

• Status: Recruiting
• Conditions: Catecholaminergic Polymorphic Ventricular Tachycardia
• Intervention / Treatment: Drug: CRD-4730; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jason Homsy, MD, Ph.D.; Phone Number: 617-863-8088; Email: infoCPVT@cardurion.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Recruiting
      • Cardurion Investigative Site
• France
  • Saint-Herblain, France, 44800
    • Recruiting
    • Cardurion Investigative Site
• Italy
  • Pavia
    • Pavia, Pavia, Italy, 27100
      • Recruiting
      • Cardurion Investigative Site
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Recruiting
      • Cardurion Investigative Site
• Spain
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Recruiting
      • Cardurion Investigative Site
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • Cardurion Investigative Site
  • North Carolina
    • Morrisville, North Carolina, United States, 27560
      • Recruiting
      • Cardurion Investigative Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Cardurion Investigative Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • Cardurion Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Each participant must meet all the following criteria to be enrolled in this study:

1. The participant is male or female, ≥18 years of age and of legal adult age in accordance with local requirements.
2. The participant has a confirmed CPVT diagnosis, based on genetic screening for a pathogenic ryanodine receptor (RYR2) mutation and a clinical phenotype consistent with CPVT at Screening. Previous CPVT genetic testing documented in medical history is acceptable if confirmed by the Investigator and documented in the study source records.
3. The participant can perform an EST during which frequent premature ventricular contractions (PVCs; ≥10 per minute), ventricular bigeminy, or higher-grade VA (equivalent to a VA score ≥2) are identified by the Investigator.
4. The participant has been on a stable dose of at least 1 antiarrhythmic medication (including beta blockers but not amiodarone) for 4 weeks prior to Screening, unless the participant has been unable to tolerate antiarrhythmic therapy previously.
5. Adheres to all contraceptive criteria.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from the study:

1. The participant has clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease.
2. The participant has a clinically significant abnormal ECG not explained by the diagnosis of CPVT at Screening or clinically significant abnormal intervals, such as prolonged QT.
3. The participant has a history of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of Screening.
4. The participant undergoes implantable cardioverter-defibrillator (ICD) implantation or has sympathetic nerve denervation within 3 months of Screening.
5. The participant has an anticipated change in exercise regimen or new exercise program during the course of the study.
6. The participant has a history of malignancy within the past 5 years at Screening, with the exception of successfully treated basal cell carcinoma or nonmetastatic squamous cell carcinoma of the skin or cervical carcinoma in situ. Prior exposure to chest radiation for any malignancy is exclusionary.
7. The participant has abnormal blood pressure, defined as supine symptomatic hypotension, systolic blood pressure >150 mm Hg or diastolic blood pressure >90 mm Hg, or symptomatic bradycardia or a heart rate >100 bpm at Screening and/or on Day 1. Blood pressure and pulse should be measured after the participant has been in the seated position after 5 minutes of rest.
8. The participant has hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × (upper limit of normal [ULN]) and/or total bilirubin >1.5 × ULN at Screening (unless secondary to confirmed Gilbert syndrome).
9. The participant has acute or chronic hepatitis B (HBV; defined as hepatitis B surface antigen [HBsAg] reactive), acute or chronic hepatitis C virus (HCV; defined as detection of HCV antibody and RNA [qualitative]), or human immunodeficiency virus (HIV) infection.
10. The female participant is pregnant, lactating/breastfeeding, or has plans to become pregnant during the study or within 3 months following the last study drug administration.
11. The participant has taken any antiarrhythmic drug in addition to their stable, chronic regimen unless it has been at least 5 half-lives since administration at the time of Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1; CRD-4730 Dose 1 Tablet	Drug: CRD-4730; Oral CRD-4730 in tablet form
Experimental: Dose 2; CRD 4730 Dose 2 Tablet	Drug: CRD-4730; Oral CRD-4730 in tablet form
Placebo Comparator: Dose 3; Placebo tablet to match CRD-4730	Drug: Placebo; Placebo to match CRD-4730 in tablet form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measures	The number and severity of treatment-emergent adverse events (TEAEs) related to study drug treatment	Baseline to Day 101

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome Measure	Change in VA score during EST from baseline to Day 15, from baseline to Day 44, and from baseline to Day 73	Baseline to Day 15; Baseline to Day 44; Baseline to Day 73
Secondary Outcome Measures	Plasma concentrations of CRD-4730 over time for each treatment period	Baseline to Day 15; Baseline to Day 44; Baseline to Day 73

Collaborators and Investigators

• Sponsor: Cardurion Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Takagahara, Shuichi, et al. "Novel, Potent, and Highly Selective Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Inhibitors Reduce Substrate Phosphorylation in Rat Hearts and Prolong Survival in a Mouse Model of Severe Heart Failure." Circulation 148.Suppl_1 (2023): A12726-A12726.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Arrhythmia; Cardiovascular; Ventricular Tachycardia; Catecholaminergic Polymorphic Ventricular Tachycardia; CaMKII; CRD-4730; CPVT; CaM kinase II; Calmodulin-dependent protein kinase II
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Tachycardia; Pathological Conditions, Signs and Symptoms; Tachycardia, Ventricular; Arrhythmias, Cardiac; Polymorphic Catecholaminergic Ventricular Tachycardia
• Other Study ID Numbers: CRD-4730-202

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