A Phase 2 Study of CRD-4730 in CPVT

NCT06658899 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CRD-4730-202
• Study Type: interventional
• Target: 12
• Locations: 6 countries
• Sites: 9

Brief Summary

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.

Conditions

Catecholaminergic Polymorphic Ventricular Tachycardia

Keywords

CaMKII; CPVT; Ventricular Tachycardia; CRD-4730; Cardiovascular; Arrhythmia; Catecholaminergic Polymorphic Ventricular Tachycardia; CaM kinase II; Calmodulin-dependent protein kinase II

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measures

  The number and severity of treatment-emergent adverse events (TEAEs) related to study drug treatment

  Baseline to Day 101

Secondary Outcomes (2)

• Secondary Outcome Measure

  Baseline to Day 15; Baseline to Day 44; Baseline to Day 73

• Secondary Outcome Measures

  Baseline to Day 15; Baseline to Day 44; Baseline to Day 73

Study Arms (3)

Dose 1

EXPERIMENTAL

CRD-4730 Dose 1 Tablet

Drug: CRD-4730

Dose 2

EXPERIMENTAL

CRD 4730 Dose 2 Tablet

Drug: CRD-4730

Dose 3

PLACEBO COMPARATOR

Placebo tablet to match CRD-4730

Drug: Placebo

Interventions

CRD-4730 DRUG

Oral CRD-4730 in tablet form

Dose 1; Dose 2

Placebo DRUG

Placebo to match CRD-4730 in tablet form

Dose 3

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each participant must meet all the following criteria to be enrolled in this study:
• The participant is male or female, ≥18 years of age and of legal adult age in accordance with local requirements.
• 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.
• 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.
• 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.
• Adheres to all contraceptive criteria.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• The participant has clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease.
• 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.
• The participant has a history of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of Screening.
• The participant undergoes implantable cardioverter-defibrillator (ICD) implantation or has sympathetic nerve denervation within 3 months of Screening.
• The participant has an anticipated change in exercise regimen or new exercise program during the course of the study.
• 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.
• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Cardurion Pharmaceuticals, Inc.: lead

Study Sites (9)

Cardurion Investigative Site

San Francisco, California, 94143, United States

RECRUITING

Cardurion Investigative Site

Morrisville, North Carolina, 27560, United States

RECRUITING

Cardurion Investigative Site

Houston, Texas, 77030, United States

RECRUITING

Cardurion Investigative Site

Madison, Wisconsin, 53792, United States

RECRUITING

Cardurion Investigative Site

Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

Cardurion Investigative Site

Saint-Herblain, 44800, France

RECRUITING

Cardurion Investigative Site

Pavia, Pavia, 27100, Italy

RECRUITING

Cardurion Investigative Site

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

Cardurion Investigative Site

Esplugues de Llobregat, Barcelona, 08950, Spain

RECRUITING

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

Polymorphic Catecholaminergic Ventricular Tachycardia; Tachycardia, Ventricular; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Tachycardia; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jason Homsy, MD, Ph.D.

CONTACT

617-863-8088; infoCPVT@cardurion.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator, Subject, Outcomes Assessor, and Sponsor Blinded; placebo-controlled
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3-period randomized 3-sequence study

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: October 26, 2024
• Study Start: December 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); US (4); IT (1); FR (1); ES (1); CA (1)