CardiolRx in Recurrent Pericarditis Following IL-1 Blocker Cessation

Phase 3

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 - 16 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, randomized, 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.

Before any trial-related procedure is performed, written informed consent will be obtained. After informed consent is obtained, patients will be screened for eligibility.

The highest NRS pain score within the past 7 days is to be assessed prior to randomization at Visit 1 (Day 1). Baseline blood samples for central laboratory assessment of hs-CRP and pharmacokinetic assessments should also be collected prior to randomization at Visit 1 (Day 1).

All other screening assessments will be performed at any time within 7 days prior to randomization at Visit 1 (Day 1) and include the following: Physical examination, vital signs, 12-lead ECG; C-SSRS and blood draws for local laboratory assessments (see Section 17.2).

Eligible patients will be randomized at Visit 1 (Day 1) to either CardiolRx or matching placebo in a 1:1 ratio. Double-blind trial therapy will be initiated in the evening of Day 1, 10 - 16 days (no additional time window is allowed) 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.

Vital signs, ECG recording and blood draws for local and central laboratory analyses will be carried out at selected visits. Concomitant medications and (S)AEs will be recorded at all visits.

Final efficacy assessments will take place at Visit 9, 24 weeks after randomization and start of trial therapy and include a physical exam, vital signs, pain score NRS collection, a 12-lead ECG, a C-SSRS, as well as blood draws for local and central laboratory assessments.

A virtual safety follow-up visit (Visit 10) 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
• Study Start: 2025-04-07
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-22
• Last Update Posted: 2025-08-28
• Primary Completion: 2026-09-21
• Study Completion: 2026-10-21

Recruitment & Eligibility

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

Inclusion Criteria

1. Patients 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 les or equal than 2 on the 11-point Numerical Rating Scale (NRS) for at least 7 days prior to randomization (Visit 1, Day 1)

4. C-Reactive Protein (CRP) < 1.0 mg/dL during screening within 7 days prior to randomization (Visit 1, Day 1).

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

6. Patients of childbearing potential willing to use an acceptable method of contraception starting with trial therapy administration and for a minimum of 2 months after trial completion. Otherwise, these patients 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.

Acceptable birth control methods that result in a failure rate of less than 1 % include oral, intravaginal or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); using double-barrier contraception methods with their partners; bilateral tubal occlusion; vasectomised partner; sexual abstinence.

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 during screening within 7 days prior to randomization (Visit 1, Day 1)

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 during screening within 7 days prior to randomization (Visit 1, Day 1).

6. Sepsis, defined as documented bacteremia during screening within 7 days prior to randomization (Visit 1, Day 1) 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 > 480 msec (biologically female) or > 470 msec (biologically male) (please refer to Section 9.2.3 for bundle branch block, bifascicular block and paced rhythm correction) or second or third degree atrioventricular (AV) block in a patient without an implanted functioning pacemaker device during screening within 7 days prior to randomization (Visit 1, Day 1)

10. Showing suicidal tendency during the last 12 months, as defined by answering "yes" to question 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS), administered during screening within 7 days prior to randomization (Visit 1, Day 1)

11. Participation in a clinical trial in which an investigational drug or device was administered within 30 days of screening or within 5 half-lives of the previous study drug, whichever is longer

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 or unwilling to stay abstinent from all cannabis products for the duration of the trial

15. Pregnant or breastfeeding

16. Current diagnosis of active 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 as below prior to randomization:

    1. Methotrexate (within 2 weeks)
    2. Azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, or mercaptopurine (within 24 weeks)
    3. Canakinumab, TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors (within 12 weeks)
    4. Intravenous immune globulin (IVIG) (within 8 weeks)
    5. Corticosteroids (within 4 weeks)

20. Known hypersensitivity to the active substance or any of the excipients of the trial

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
Percentage of days with no or minimal pain	24 weeks	the percentage of days with no or minimal pain as assessed by an NRS score ≤ 2 from the timepoint of stopping the IL-1 blocker to Visit 9 (Week 24)

Trial Locations

Locations (22)

UCI Health; 🇺🇸 Irvine, California, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

MedStar Health Institute; 🇺🇸 Columbia, Maryland, United States

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

Minneapolis Heart Institute; 🇺🇸 Minneapolis, Minnesota, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

Columbia University - New York Presbyterian; 🇺🇸 New York, New York, United States

Lenox Hill Hospital; 🇺🇸 New York, New York, United States

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