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

Heart Diseases Clinical Trial

— CPVT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06005428
• Other study ID #: CRD-4730-201
• Status: Recruiting
• Phase: Phase 2
• Start date: November 7, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Cardurion Pharmaceuticals, Inc.
• Contact: Jason Homsy, M.D., Ph.D.
• Phone: (617) 863-8088
• Email: jason.homsy[@]cardurion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2024
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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. Ability to perform an Exercise Stress Test (EST) during which exercise-induced ventricular couplets or higher-grade VA (equivalent to a VA score =3) 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.

Related Conditions & MeSH terms

• Congenital Abnormalities
• Heart Defects, Congenital
• Heart Diseases
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Tachycardia

Intervention

Drug:
• CRD-4730
Oral CRD-4730 in capsule form
• Placebo
Placebo to match CRD-4730 in capsule form

Locations

Country	Name	City	State
Canada	Cardurion Investigative Site	Edmonton	Alberta
Canada	Cardurion Investigative Site	London	Ontario
Canada	Cardurion Investigative Site	Vancouver	British Columbia
Canada	Cardurion Investigative Site	Vancouver	British Columbia
France	Cardurion Investigative Site	Bron
France	Cardurion Investigative Site	Nantes	Loire-Atlantique
France	Cardurion Investigative Site	Paris
France	Cardurion Investigative Site	Saint-Herblain
Italy	Cardurion Investigative Site	Pavia	Lombardia
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cardurion Investigative Site	Cleveland	Ohio
United States	Cardurion Investigative Site	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Cardurion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Changes in Vital Signs Measurement: Pulse Rate	Percent change from Baseline to post Baseline will be assessed for pulse rate	Baseline to Day 15
Primary	Changes in Vital Signs Measurement: Respiratory Rate	Percent change from Baseline to post Baseline will be assessed for respiratory rate	Baseline to Day 15
Primary	Changes in Vital Signs Measurement: Body Temperature	Percent change from Baseline to post Baseline will be assessed for body temperature	Baseline to Day 15
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Assessment of PK effect	Plasma concentrations of CRD-4730 over time for each treatment period	Baseline through Day 15