Effectiveness of Repeat-dose CRD-4730 in Participants with CPVT

Phase 2

Not yet recruiting

• Conditions: Catecholaminergic Polymorphic Ventricular Tachycardia
• Interventions: Drug: CRD-4730; Drug: Placebo

• Registration Number: NCT06658899
• 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). The study will have 3 cohorts in which participants with CPVT will participate in a 3-period, randomized 3-sequence study. Each participant will receive 2 different doses of CRD-4730 and 1 dose of matching placebo.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-23
• Study First Submitted QC: 2024-10-23
• Study First Posted: 2024-10-26
• Last Update Submitted: 2024-10-31
• Last Update Posted: 2024-11-01
• Study Start: 2025-05
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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
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

Arm && Interventions

Group	Intervention	Description
Dose 1	CRD-4730	CRD-4730 Dose 1 Tablet
Dose 2	CRD-4730	CRD 4730 Dose 2 Tablet
Dose 3	Placebo	Placebo tablet to match CRD-4730

Primary Outcome Measures

Name	Time	Method
Primary Outcome Measures	Baseline to Day 77	The number of participants with the treatment-emergent adverse events (TEAEs) related to study drug treatment by severity

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome Measure	Baseline to Day 7; Baseline to Day 28; Baseline to Day 49	Mean change in VA score during EST from baseline to Day 7, from baseline to Day 28, and from baseline to Day 49
Secondary Outcome Measures	Baseline to Day 7; Baseline to Day 28; Baseline to Day 49	Concentration of CRD-4730 in plasma over time for each treatment period