Clinical trial NCT06005428: Effectiveness of CRD-4730 in Participants with Catecholaminergic Polymorphic Ventricular Tachycardia (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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: CPVT1
Heart Defects, Congenital
Heart Diseases
Ventricular Tachycardia
Keywords: CaMKII
Catecholaminergic polymorphic VT
Ventricular Tachycardia
CRD-4730
Lead sponsor: Cardurion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 3-period randomized 2-sequence study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline to Day 22
measure: Changes in Laboratory Assessments
timeFrame: Baseline to Day 15
measure: Changes in Vital Signs Measurement: Systolic and Diastolic blood pressure
timeFrame: Baseline to Day 15
measure: Changes in Vital Signs Measurement: Pulse Rate
timeFrame: Baseline to Day 15
measure: Changes in Vital Signs Measurement: Respiratory Rate
timeFrame: Baseline to Day 15
measure: Changes in Vital Signs Measurement: Body Temperature
timeFrame: Baseline to Day 15
measure: Changes in Physical Exam
timeFrame: Baseline to Day 22
measure: Changes in Electrocardiogram (ECG) Measurements
timeFrame: Baseline to Day 22
Secondary outcomes:
measure: Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)
timeFrame: Baseline to Day 1
measure: Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)
timeFrame: Baseline to Day 8
measure: Change in Ventricular Arrhythmia (VA) score during Exercise Stress Test (EST)
timeFrame: Baseline to Day 15
measure: Assessment of PK effect
timeFrame: Baseline through Day 15
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children&#39;s Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Children&amp;#39;s Hospital
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Edmonton
country: Canada
facility: Stollery Children&amp;#39;s Hospital University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia (UBC) Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Children&amp;#39;s Hospital
state: British Columbia
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
city: Nantes
country: France
facility: Hôptal Nord Laennec
state: Loire-Atlantique
city: Bron
country: France
facility: Hôpital Louis Pradel
city: Paris
country: France
facility: Groupe Hospitalier Bichat Claude Bernard
city: Pavia
country: Italy
facility: IRCCS Pavia Istituti Clinici Scientifici Maugeri Spa Società Benefit
state: Lombardia
Study officials:
affiliation: Executive Medical Director
name: Jason Homsy, M.D., Ph.D.
role: STUDY_DIRECTOR
References: