CRD-4730 for Catecholaminergic Polymorphic Ventricular Tachycardia

(CPVT Trial)

Recruiting at 21 trial locations

Overseen By Jason Homsy, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cardurion Pharmaceuticals, Inc.

Must be taking: Anti-arrhythmics

Must not be taking: Amiodarone

Disqualifiers: Heart disease, Heart failure, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 3 periods

12 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You can continue taking your current anti-arrhythmic medications, except for amiodarone, as long as the doses have been stable for at least 4 weeks before the study.

How is the drug CRD-4730 different from other treatments for catecholaminergic polymorphic ventricular tachycardia?

CRD-4730 is a novel treatment being tested for catecholaminergic polymorphic ventricular tachycardia, a condition that currently relies on β-blockers and implantable cardioverter-defibrillators (ICDs) for management. Unlike existing treatments, CRD-4730 may offer a new approach, potentially targeting different mechanisms or providing an alternative for patients who do not respond well to current therapies. ^{1 2 3 4 5}

Research Team

Jason Homsy, M.D., Ph.D.

Principal Investigator

Executive Medical Director

Eligibility Criteria

Adults over 18 with confirmed CPVT, a heart condition causing irregular rapid heartbeats, can join. They must be able to do an exercise test and have been on stable doses of anti-arrhythmic meds (except amiodarone) for 4 weeks. Participants need to follow strict birth control rules.

Inclusion Criteria

I have been diagnosed with CPVT through genetic testing and clinical assessment.

I have been on a steady dose of heart rhythm medication, not including amiodarone, for the last 4 weeks.

You are capable of completing an EST that results in the detection of ventricular couplets or a VA score higher than 3 by the researcher.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 different doses of CRD-4730 and 1 dose of matching placebo, each as a single dose

3 periods

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in vital signs, ECG, and laboratory assessments

22 days

2 visits (in-person)

Treatment Details

Interventions

• CRD-4730
• Placebo

Trial Overview The trial tests CRD-4730's safety and effects in people with CPVT compared to a placebo. It's double-blind, meaning neither the participants nor the researchers know who gets the real drug or placebo during the study.

Participant Groups

Group I: Dose 2 Experimental Treatment 1 Intervention

CRD-4730 Dose 2 capsule

Group II: Dose 1 Experimental Treatment 1 Intervention

CRD-4730 Dose 1 capsule

Group III: Dose 3 Placebo Group 1 Intervention

Placebo capsule to match CRD-4730

Who Is Running the Clinical Trial?

Cardurion Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

740+

Findings from Research

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a serious heart condition that can cause dangerous arrhythmias during stress or exercise, as demonstrated in a case of an adolescent with recurrent fainting episodes.

The diagnosis was confirmed through genetic testing revealing a mutation in the cardiac ryanodine receptor gene, and the patient successfully managed the condition with antiarrhythmic medications and an implantable cardioverter-defibrillator, highlighting the importance of early detection and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Catecholaminergic polymorphic ventricular tachycardia in adolescents: a clinical, electrocardiographic and genetic diagnosis]. Rocha-Arrieta, MC., Arias-Díaz, A., Quiróz-Romero, CA., et al.[2023]

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but serious heart condition that can lead to sudden cardiac death, especially in young individuals without structural heart disease, triggered by stress or exercise.

Diagnosing CPVT in emergency settings is challenging due to its varied presentations, making it essential for healthcare providers to be aware of its symptoms and management strategies to prevent life-threatening arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catecholaminergic polymorphic ventricular tachycardia, an update. Pérez-Riera, AR., Barbosa-Barros, R., de Rezende Barbosa, MPC., et al.[2021]

Left cardiac sympathetic denervation (LCSD) provided short-term relief from symptoms and exercise-induced ventricular arrhythmia in three patients with calsequestrin (CASQ2) mutation-associated catecholaminergic polymorphic ventricular tachycardia (CPVT).

However, all patients experienced a recurrence of symptoms and arrhythmia within 6 to 18 months after the procedure, indicating that while LCSD can be effective initially, its long-term efficacy is limited for this specific condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Cardiac Sympathetic Denervation in Patients with CASQ2-Associated Catecholaminergic Polymorphic Ventricular Tachycardia. Marai, I., Boulos, M., Khoury, A.[2015]

In a study of 34 patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), treatment with nadolol significantly reduced the severity of ventricular arrhythmias during exercise compared to treatment with β1-selective β-blockers, indicating nadolol may be more effective in managing arrhythmias in these patients.

Before starting β-blocker treatment, the severity of arrhythmias was similar to that seen with β1-selective β-blockers, suggesting that these medications do not improve arrhythmia severity compared to no treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia. Leren, IS., Saberniak, J., Majid, E., et al.[2016]

Left cardiac sympathetic denervation (LCSD) significantly reduces major cardiac events in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), with a reduction from 100% to 32% in events despite optimal medical therapy after the procedure.

In patients with implantable cardioverter-defibrillators (ICDs), the rate of shocks dropped by 93% after LCSD, indicating it can effectively complement existing treatments for recurrent arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation. De Ferrari, GM., Dusi, V., Spazzolini, C., et al.[2016]

References

1. Peru pubmed.ncbi.nlm.nih.gov

[Catecholaminergic polymorphic ventricular tachycardia in adolescents: a clinical, electrocardiographic and genetic diagnosis]. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Catecholaminergic polymorphic ventricular tachycardia, an update. [2021]

3. Israel pubmed.ncbi.nlm.nih.gov

Left Cardiac Sympathetic Denervation in Patients with CASQ2-Associated Catecholaminergic Polymorphic Ventricular Tachycardia. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation. [2016]