CardiolRx in Recurrent Pericarditis Following IL-1 Blocker Cessation

Phase 3

Not yet recruiting

• Conditions: Recurrent Pericarditis
• Interventions: Drug: CardiolRx

• Registration Number: NCT06708299
• Lead Sponsor: Cardiol Therapeutics Inc.

Brief Summary

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.

Detailed Description

Double-blind, randomised, placebo-controlled Phase-3 trial. The primary objective is to assess whether patients with IL-1 blocker-dependent recurrent pericarditis can discontinue IL-1 blocker therapy and remain free of recurrence while receiving CardiolRx.

After informed consent is obtained, patients will be screened for eligibility. Baseline assessments will be performed during screening within 7 days of Day 1 (Visit 1) and include the following: Physical examination, vital signs, highest NRS pain score within the past 7 days of Day 1, 12-lead ECG; hematology (CBC with differential) and blood chemistry (including complete metabolic panel: sodium, potassium, calcium, glucose, ALT/AST, bilirubin, alkaline phosphatase, blood urea nitrogen (BUN), creatinine/eGFR), C-SSRS and a pregnancy test for women of childbearing potential.

Eligible patients will be randomized on Day 1 to either CardiolRx or matching placebo. Double-blind trial therapy will be initiated in the evening of Day 1, 10 - 14 days prior to the last scheduled dose of the IL-1 blocker and after all baseline assessments are completed. Trial therapy will be administered for 24 weeks.

Final efficacy assessments will take place 24 weeks after starting trial therapy and include a physical exam, vital signs, pain score NRS, a 12-lead ECG, as well as laboratory assessments (including a pregnancy test in women of childbearing potential) and a C-SSRS.

A safety follow-up visit will be scheduled 4 weeks after the last trial therapy administration.

Study Timeline

• Study First Submitted: 2024-11-25
• Study First Submitted QC: 2024-11-25
• Study First Posted: 2024-11-27
• Status Verified: 2024-12
• Study Start: 2024-12-15
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-24
• Primary Completion: 2026-06-15
• Study Completion: 2026-07-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

1. Male or female 18 years of age or older

2. A history of recurrent pericarditis* with stable disease and currently being treated with an IL-1 blocker, scheduled to be discontinued. Stable disease is defined as:

   • treatment with an IL-1 blocker for at least 12 months;
   • free of pericarditis recurrence for at least 6 months and this recurrence, if present, must have occurred in the setting of an interruption or tapering of an IL-1 blocker; and
   • treatment with an unchanged dose and regimen of on an IL-1 blocker for at least 3 months prior to randomization.

3. Pericarditis pain more or equal than 2 on the 11-point Numerical Rating Scale (NRS) for at least the prior 7 days

4. C-Reactive Protein (CRP**) < 1.0 mg/dL within the 7 days of screening prior to Day 1 (Visit 1)

5. Male patients with partners of childbearing potential who have had a vasectomy or who are willing to use double barrier contraception methods during the conduct of the trial and for 2 months after the last dose of trial therapy

6. Women of childbearing potential willing to use an acceptable method of contraception starting with trial drug administration and for a minimum of 2 months after trial completion. Otherwise, women must be postmenopausal (at least 1 year absence of vaginal bleeding or spotting and confirmed by follicle stimulating hormone [FSH] ≥40 mIU/mL [or ≥ 40 IU/L] if less than 2 years postmenopausal) or be surgically sterile.

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Exclusion Criteria

1. Pericarditis recurrence(s) during IL-1 blocker treatment without interruption or tapering of the IL-1 blocker

2. Diagnosis of pericarditis that is secondary to specific prohibited etiologies, including tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma (e.g., motor vehicle accident); systemic autoimmune disease (e.g., systemic lupus erythematosus)

3. Primary diagnosis of myocarditis (diagnosis of myopericarditis is accepted)

4. Estimated glomerular filtration rate (eGFR) < 30 mL/min at baseline

5. Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN) or ALT or AST > 3x ULN plus bilirubin > 2x ULN

6. Sepsis, defined as documented bacteremia at baseline or other untreated or uncontrolled bacterial infection*

7. Prior history of sustained ventricular arrhythmia(s)

8. History of diagnosed long QT syndrome

9. QTc interval > 500 msec at baseline

10. Showing suicidal tendency, as defined by answering "yes" to question 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS), administered at baseline

11. Currently participating in any research trial involving investigational drugs or devices

12. Inability or unwillingness to give informed consent

13. Ongoing drug or alcohol abuse in the opinion of the investigator

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

15. Pregnant or breastfeeding

16. Current diagnosis of cancer, with the exception of non-melanoma skin cancer

17. Any factor, which would make it unlikely that the patient can comply with the trial procedures

18. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment

19. Has received systemic immunomodulatory agents prior to randomization:

    1. Methotrexate (within 2 weeks)
    2. Azathioprine (within 24 weeks)
    3. Cyclosporine (within 24 weeks)
    4. Intravenous immune globulin (IVIG) (within 8 weeks)
    5. Corticosteroids (within 4 weeks).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CardiolRx	CardiolRx	* 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.
Placebo	CardiolRx	* 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.

Primary Outcome Measures

Name	Time	Method
Recurrence of pericarditis	24 weeks	proportions of patients free from a new episode of recurrent pericarditis\* from the timepoint of stopping the IL-1 blocker to Week 24

Secondary Outcome Measures

Name	Time	Method
Time to pericarditis recurrence	24 weeks	the median time to a new episode of pericarditis recurrence from the timepoint of stopping the IL-1 blocker to Week 24

Trial Locations

Locations (5)

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States