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

Sponsor

Cardurion Pharmaceuticals, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06005428

Collaborator

(none)

Enrollment

Arms

15.5

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
CPVT1 Heart Defects, Congenital Heart Diseases Ventricular Tachycardia	Drug: CRD-4730 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

3-period randomized 2-sequence study3-period randomized 2-sequence study

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Investigator and Subject Blinded, Sponsor Unblinded; Placebo-controlled

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 15, 2023

Anticipated Primary Completion Date :

Nov 29, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 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
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

Secondary Outcome Measures

Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST) [Baseline to Day 1]
The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse.
Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST) [Baseline to Day 8]
The VA score is a physician administered score on a scale of 0-5 with higher numbers being worse.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or Females ≥18 years of age, at screening.
Confirmed CPVT diagnosis, based on genetic screening for a known RyR2 mutation and a clinical phenotype consistent with CPVT at screening.
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.
Stable doses of any anti-arrhythmic medication, except amiodarone, for 4 weeks prior to screening.
Adhere to all contraceptive criteria.

Exclusion Criteria:

Clinically significant structural heart disease, diagnosis of heart failure, or clinically significant coronary artery disease.
History of a myocardial infarction, cerebrovascular accident, or transient ischemic attack within 3 months of screening.
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).
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.
Use of amiodarone with 3 months prior to screening. NOTE: other protocol defined Inclusion/ Exclusion criteria may apply.