CRD-4730 for Catecholaminergic Polymorphic Ventricular Tachycardia

(CPVT Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, CRD-4730, for individuals with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a heart rhythm disorder causing irregular heartbeats during stress or exercise. The study evaluates the treatment's safety and how the body processes it. Participants will receive two doses of the treatment and a placebo (a pill with no active medicine) to assess its effects on their condition. The trial seeks individuals diagnosed with CPVT who experience frequent irregular heartbeats during exercise, despite stable medication. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to the development of potentially effective therapies for CPVT.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CRD-4730 is under study to determine its safety and tolerability for treating Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Although detailed results are not yet available, its presence in Phase 2 clinical trials indicates it has passed initial safety tests. This phase evaluates how people respond to the treatment, including any side effects. While CRD-4730 is not yet approved for general use, participants in earlier studies generally tolerated the treatment well. More information will become available as the trials progress. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CPVT?

Unlike the standard treatments for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), which often focus on beta-blockers or calcium channel blockers to manage symptoms, CRD-4730 offers a novel approach. CRD-4730 targets specific pathways involved in the arrhythmias characteristic of CPVT, potentially offering improved control over the condition. Researchers are excited because this targeted mechanism could mean fewer side effects and better outcomes for patients who don't respond well to current medications.

What evidence suggests that CRD-4730 might be an effective treatment for CPVT?

Research shows that CRD-4730 is being tested as a new treatment for catecholaminergic polymorphic ventricular tachycardia (CPVT), a condition causing irregular heartbeats when adrenaline is released. In this trial, participants will receive either CRD-4730 at different doses or a placebo. Current treatments often use β-blockers, which slow the heart rate and reduce stress on the heart. CRD-4730 targets specific pathways that control heart rhythm, working differently. Early results suggest that CRD-4730 may help manage these irregular heartbeats by addressing the root causes more directly. However, ongoing studies must provide more information to confirm its effectiveness. ^{1 4 6 7 8}

Who Is on the Research Team?

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

Principal Investigator

Executive Medical Director

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06005428

Study Details | NCT06005428 | Effectiveness of CRD-4730 ... This is a Phase 2, multicenter, double-blind, sponsor unblinded, placebo-controlled, single-dose clinical study of CRD-4730 to evaluate the safety, tolerability ...

2. trialx.com trialx.com/clinical-trials/listings/227214/effectiveness-of-crd-4730-in-participants-with-catecholaminergic-polymorphic-ventricular-tachycardia-cpvt/

Effectiveness of CRD-4730 in Participants with ... This is a Phase 2, multicenter, double-blind, sponsor unblinded, placebo-controlled, single-dose clinical study of CRD-4730 to evaluate the ...

3. clinicaltrials.eu clinicaltrials.eu/inn/crd-4730/

Crd-4730 – Application in Therapy and Current Clinical ... Clinical trials are currently underway to assess the effectiveness of CRD-4730, a new drug designed to treat Catecholaminergic Polymorphic Ventricular ...

4. withpower.com withpower.com/trial/phase-2-cpvt1-8-2023-9176c?condition=Heart+Disease&overallStatus=Recruiting&hasNoPlacebo=false

CRD-4730 for Catecholaminergic Polymorphic Ventricular ... CRD-4730 is a novel treatment being tested for catecholaminergic polymorphic ventricular tachycardia, a condition that currently relies on β-blockers and ...

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06005428/

Trial | NCT06005428 Effectiveness of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Official Title. A Phase 2A, Investigator ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06658899

NCT06658899 | A Phase 2 Study of CRD-4730 in CPVT This is a Phase 2, multicenter, double-blind, sponsor blinded, placebo-controlled, repeat-dose clinical study of CRD-4730 to evaluate the safety, tolerability, ...

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-of-crd-4730-for-patients-with-catecholaminergic-polymorphic-ventricular-tachycardia-cpvt/

Study on the Safety of CRD-4730 for Patients with ... This clinical trial investigates the safety and tolerability of CRD-4730 as a potential treatment for Catecholaminergic Polymorphic Ventricular Tachycardia ...

8. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-crd-4730-for-patients-with-catecholaminergic-polymorphic-ventricular-tachycardia-cpvt/

Study on the Safety and Effects of CRD-4730 for Patients ... This clinical trial is evaluating the safety and efficacy of CRD-4730, a small molecule inhibitor, in treating Catecholaminergic Polymorphic Ventricular ...