A Phase 2 Study of CRD-4730 in CPVT

Phase 2

Not yet recruiting

• Conditions: Catecholaminergic Polymorphic Ventricular Tachycardia

• Registration Number: 2024-515564-32-00
• Lead Sponsor: Cardurion Pharmaceuticals Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-23
• Study First Submitted QC: 2024-10-23
• Study First Posted: 2024-10-26
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-14
• Last Update Posted: 2025-08-19
• Study Start: 2025-12-01
• Primary Completion: 2027-04
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 6

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb; 🇮🇹 Pavia, Italy

Hospital Sant Joan De Deu Barcelona; 🇪🇸 Esplugues De Llobregat, Spain

Amsterdam UMC Stichting; 🇳🇱 Amsterdam, Netherlands

Centre Hospitalier Universitaire De Nantes; 🇫🇷 Saint Herblain, France

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris Cedex 18, France

Hospices Civils De Lyon; 🇫🇷 Bron, France

Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb

🇮🇹Pavia, Italy

Silvia Giuliana Maria Luigina PRIORI

Site contact

+390382592774

silvia.priori@icsmaugeri.it