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

A Phase 2A, Investigator & Subject Blinded, Sponsor Unblinded, Placebo-Controlled, Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia

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.

Study Overview

• Status: Terminated
• Conditions: Heart Diseases; Ventricular Tachycardia; Heart Defects, Congenital; CPVT1
• Intervention / Treatment: Drug: CRD-4730; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R7
      • Stollery Children's Hospital University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • University of British Columbia (UBC) Hospital
    • Vancouver, British Columbia, Canada, V6H 3N1
      • British Columbia Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • University of Western Ontario
• France
  • Bron, France, 69677
    • Hopital Louis Pradel
  • Paris, France, 75018
    • Groupe Hospitalier Bichat Claude Bernard
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44805
      • Hôptal Nord Laennec
• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • IRCCS Pavia Istituti Clinici Scientifici Maugeri Spa Società Benefit
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

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

Description

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 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 capsule	Drug: CRD-4730; Oral CRD-4730 in capsule form
Experimental: Dose 2; CRD-4730 Dose 2 capsule	Drug: CRD-4730; Oral CRD-4730 in capsule form
Placebo Comparator: Dose 3; Placebo capsule to match CRD-4730	Drug: Placebo; Placebo to match CRD-4730 in capsule form

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)	The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse.	Baseline to Day 1
Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)	The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse.	Baseline to Day 8
Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)	The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse.	Baseline to Day 15
Assessment of PK effect	Plasma concentrations of CRD-4730 over time for each treatment period	Baseline through Day 15

Collaborators and Investigators

• Sponsor: Cardurion Pharmaceuticals, Inc.
• Investigators: Study Director: Jason Homsy, M.D., Ph.D., Executive Medical Director

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Actual): May 31, 2025
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ventricular Tachycardia; CaMKII; Catecholaminergic polymorphic VT; CRD-4730
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Arrhythmias, Cardiac; Congenital Abnormalities; Cardiovascular Abnormalities; Tachycardia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Heart Diseases; Heart Defects, Congenital; Tachycardia, Ventricular
• Other Study ID Numbers: CRD-4730-201

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