Effectiveness of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Phase 2

Recruiting

• Conditions: CPVT1; Heart Defects, Congenital; Heart Diseases; Ventricular Tachycardia
• Interventions: Drug: CRD-4730; Drug: Placebo

• Registration Number: NCT06005428
• Lead Sponsor: Cardurion Pharmaceuticals, Inc.

Brief Summary

This is a Phase 2, multicenter, double-blind, sponsor unblinded, placebo-controlled, single-dose clinical study of CRD-4730 to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CRD-4730 when administered as single oral doses to participants with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The study will have 2 cohorts in which participants with CPVT will participate in a 3-period, randomized 2-sequence study. Each participant will receive 2 different doses of CRD-4730 and 1 dose of matching placebo, with each study drug administered as a single dose.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-08
• Study First Submitted QC: 2023-08-17
• Study First Posted: 2023-08-22
• Study Start: 2023-11-07
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-17
• Last Update Posted: 2025-01-20
• Primary Completion: 2025-07-31
• Study Completion: 2025-09-30

Recruitment & Eligibility

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

Inclusion Criteria

1. Males or Females ≥18 years of age, at screening.
2. Confirmed CPVT diagnosis, based on genetic screening for a known RyR2 mutation and a clinical phenotype consistent with CPVT at screening.
3. The participant can perform an EST during which frequent premature ventricular contraction (PVCs) (≥10 per minute), ventricular bigeminy, or higher-grade VA (equivalent to a VA score ≥2) are identified by the investigator.
4. Stable doses of any anti-arrhythmic medication, except amiodarone, for 4 weeks prior to screening.
5. Adhere to all contraceptive criteria.

Exclusion Criteria

1. Clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease.
2. History of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of screening.
3. History of malignancy within the past 5 years at screening (except successfully treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ).
4. Female participant that is pregnant or lactating/ breastfeeding, or has plans to do so during the study or within 3 months following last dose of study drug.
5. Use of amiodarone with 3 months prior to screening. NOTE: other protocol defined Inclusion/ Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Events (TEAEs)	Baseline to Day 22	The number of participants with TEAEs including drug-related AEs, serious AEs (SAEs), and AEs leading to study drug discontinuation will be assessed.
Changes in Laboratory Assessments	Baseline to Day 15	The number of participants who have normal/ abnormal values at Baseline compared to normal/ abnormal values post-Baseline will be assessed for hematology, serum chemistry and urinalysis.
Changes in Vital Signs Measurement: Systolic and Diastolic blood pressure	Baseline to Day 15	Percent change from Baseline to post Baseline will be assessed for systolic and diastolic blood pressure
Changes in Electrocardiogram (ECG) Measurements	Baseline to Day 22	Number of participants who have normal/abnormal ECG measurements at Baseline will be compared to normal/abnormal ECG measurement post Baseline
Changes in Vital Signs Measurement: Pulse Rate	Baseline to Day 15	Percent change from Baseline to post Baseline will be assessed for pulse rate
Changes in Vital Signs Measurement: Respiratory Rate	Baseline to Day 15	Percent change from Baseline to post Baseline will be assessed for respiratory rate
Changes in Vital Signs Measurement: Body Temperature	Baseline to Day 15	Percent change from Baseline to post Baseline will be assessed for body temperature
Changes in Physical Exam	Baseline to Day 22	General physical exams will be carried out to detect any abnormalities in the cardiovascular, respiratory and other body systems

Secondary Outcome Measures

Name	Time	Method
Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)	Baseline to Day 15	The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse.
Assessment of PK effect	Baseline through Day 15	Plasma concentrations of CRD-4730 over time for each treatment period

Trial Locations

Locations (11)

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Stollery Children's Hospital University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

University of British Columbia (UBC) Hospital; 🇨🇦 Vancouver, British Columbia, Canada

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

University of Western Ontario; 🇨🇦 London, Ontario, Canada

Hôptal Nord Laennec; 🇫🇷 Nantes, Loire-Atlantique, France

Hôpital Louis Pradel; 🇫🇷 Bron, France

Groupe Hospitalier Bichat Claude Bernard; 🇫🇷 Paris, France

IRCCS Pavia Istituti Clinici Scientifici Maugeri Spa Società Benefit; 🇮🇹 Pavia, Lombardia, Italy