CardiolRx for Pericarditis

(MAVERIC Trial)

Recruiting at 6 trial locations

Overseen By Heather Dalgleish, MSc.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cardiol Therapeutics Inc.

Must be taking: IL-1 blockers

Must not be taking: Cannabinoids, Methotrexate

Disqualifiers: Cancer, Sepsis, Myocarditis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

110 Participants Needed

Trial Summary

What is the purpose of this trial?

Multi-center, randomized, double-blind, placebo-controlled, phase-3 Trial. Patients with a history of recurrent pericarditis who are being treated with an IL-1 blocker for at least 12 months, scheduled to be discontinued, will be approached for potential trial participation. Double-blind treatment will be initiated 10 - 14 days prior to the last scheduled dose of the IL-1 blocker and continued for 24 weeks. The objective is to assess whether patients who discontinue therapy with an IL-1 blocker for recurrent pericarditis remain free of pericarditis recurrence while receiving CardiolRx.

Will I have to stop taking my current medications?

Participants will need to stop taking their IL-1 blocker as part of the trial. The trial does not specify if other medications need to be stopped, but certain immunomodulatory agents must not have been used recently before joining the trial.

What safety data exists for CardiolRx or similar treatments?

The research articles provided do not contain specific safety data for CardiolRx or similar treatments. ^{1 2 3 4 5}

Research Team

Paul Cremer, MD

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for patients with recurrent pericarditis who have been on an IL-1 blocker for at least a year and are planning to stop the medication. They will be part of a study that tests if CardiolRx can prevent their pericarditis from coming back after stopping the IL-1 blocker.

Inclusion Criteria

C-Reactive Protein (CRP) less than 1.0 mg/dL within the 7 days of screening prior to Day 1 (Visit 1)

I am 18 years old or older.

I have recurring pericarditis, currently managed with an IL-1 blocker, which I plan to stop.

Exclusion Criteria

QTc interval greater than 500 msec at baseline

Pregnant or breastfeeding

On any cannabinoid during the past month and unwilling to stay abstinent from all cannabis products for the duration of the trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive double-blind trial therapy with CardiolRx or placebo for 24 weeks

24 weeks

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• CardiolRx

Trial Overview The trial is testing CardiolRx, given before and after discontinuing an IL-1 blocker treatment. It's a multi-center, double-blind (neither doctors nor participants know who gets what), placebo-controlled study lasting 24 weeks to see if it prevents pericarditis recurrence.

Participant Groups

Group I: CardiolRx Active Control 1 Intervention

* Initial starting dose (Day 1, evening dose to Day 3, morning dose): 5 mg/kg of body weight CardiolRx b.i.d. * Day 3, evening dose to Day 10, morning dose: 7.5 mg/kg of body weight CardiolRx b.i.d. * Day 10, evening dose to morning dose of the Week 24 Visit: 10 mg/kg of body weight CardiolRx b.i.d.

Group II: Placebo Placebo Group 1 Intervention

* Initial starting dose (Day 1, evening dose to Day 3, morning dose): 5 mg/kg of body weight matching placebo b.i.d. * Day 3, evening dose to Day 10, morning dose: 7.5 mg/kg of body weight matching placebo b.i.d. * Day 10, evening dose to morning dose of the Week 24 Visit: 10 mg/kg of body weight matching placebo b.i.d.

Who Is Running the Clinical Trial?

Cardiol Therapeutics Inc.

Lead Sponsor

Trials

4

Recruited

330+

Findings from Research

Between 2010 and 2016, 164 safety advisories regarding cardiac-related adverse events were issued by regulators in Australia, Canada, the UK, and the US, highlighting the prevalence of risks associated with 61 different drugs, primarily involving cardiac arrhythmias and coronary artery disorders.

While monitoring patients was the most common recommendation in these advisories, only 41.2% provided detailed guidance on how to conduct this monitoring, indicating a need for more consistent and comprehensive information for healthcare professionals and consumers regarding rare but serious medication harms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. Hooimeyer, A., Bhasale, A., Perry, L., et al.[2023]

The OMERACT initiative aims to create a standardized tool for reporting adverse events in rheumatology clinical trials, which will help ensure consistent terminology and severity assessment across studies.

The proposed Rheumatology Common Toxicity Criteria Index covers multiple organ systems, but its effectiveness and practicality must be validated in clinical trials before widespread adoption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies. Woodworth, TG., Furst, DE., Strand, V., et al.[2007]

A new semi-mechanistic modeling platform was developed to assess cardiovascular safety by evaluating changes in contractility, heart rate, and mean arterial pressure in preclinical studies using data from 27 dogs and various drugs.

The model effectively accounted for factors like preload effects on heart contractility, allowing for a comprehensive evaluation of drug-induced cardiovascular changes, which is crucial for ensuring the safety of new medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semi-mechanistic modelling platform to assess cardiac contractility and haemodynamics in preclinical cardiovascular safety profiling of new molecular entities. Venkatasubramanian, R., Collins, TA., Lesko, LJ., et al.[2021]

Analysis of the FAERS database revealed that hydroxychloroquine (HCQ) and chloroquine (CQ) are associated with a higher reporting rate of serious cardiovascular adverse events (CVAEs), including cardiomyopathy, QT prolongation, cardiac arrhythmias, and heart failure, with significant odds ratios indicating increased risk.

CVAEs related to HCQ/CQ treatment resulted in hospitalization rates of 39% and mortality rates of 8%, highlighting the need for caution when prescribing these medications, especially in patients with pre-existing cardiac conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports. Goldman, A., Bomze, D., Dankner, R., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Possible relationship between hydroxychloroquine and electrocardiographic and echocardiographic abnormalities in patients with inflammatory rheumatic diseases--a monocentric study. [2023]

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

Regulatory post-market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies. [2023]

3. Canada pubmed.ncbi.nlm.nih.gov

Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies. [2007]

4. England pubmed.ncbi.nlm.nih.gov

Semi-mechanistic modelling platform to assess cardiac contractility and haemodynamics in preclinical cardiovascular safety profiling of new molecular entities. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports. [2022]