CardiolRx in Recurrent Pericarditis Following IL-1 Blocker Cessation

NCT ID: NCT06708299

Last Updated: 2025-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-07

Study Completion Date

2026-10-21

Brief Summary

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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

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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.

Conditions

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Recurrent Pericarditis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-blind, placebo-controlled, randomized
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
double-blind, placebo-controlled

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

CardiolRx

Intervention Type DRUG

The intervention will be administered orally (via syringe) with food twice daily.

Placebo

* 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.

Group Type PLACEBO_COMPARATOR

CardiolRx

Intervention Type DRUG

The intervention will be administered orally (via syringe) with food twice daily.

Interventions

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CardiolRx

The intervention will be administered orally (via syringe) with food twice daily.

Intervention Type DRUG

Other Intervention Names

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Pharmaceutically produced cannabidiol

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cardiol Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Cremer, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

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Mayo Clionic Arizona

Phoenix, Arizona, United States

Site Status RECRUITING

UCI Health

Irvine, California, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status RECRUITING

Mayo Clinic

Jacksonville, Florida, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status NOT_YET_RECRUITING

MedStar Health Institute

Columbia, Maryland, United States

Site Status NOT_YET_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Columbia University - New York Presbyterian

New York, New York, United States

Site Status RECRUITING

Columbia University - New York Presbyterian

New York, New York, United States

Site Status RECRUITING

Lenox Hill Hospital

New York, New York, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Houston Methodist Hospital

Houston, Texas, United States

Site Status RECRUITING

University of Utah Hospital

Salt Lake City, Utah, United States

Site Status NOT_YET_RECRUITING

University of Vermont

Burlington, Vermont, United States

Site Status RECRUITING

University of Virginia

Charlottesville, Virginia, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

Jewish General Hospital

Montreal, , Canada

Site Status RECRUITING

Hippokration General Hospital

Athens, , Greece

Site Status RECRUITING

Fatebenefratelli Hospital Milano

Milan, , Italy

Site Status NOT_YET_RECRUITING

University of Padua

Padua, , Italy

Site Status NOT_YET_RECRUITING

University Hospital

Torino, , Italy

Site Status NOT_YET_RECRUITING

University Hospital Udine

Udine, , Italy

Site Status NOT_YET_RECRUITING

Countries

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United States Canada Greece Italy

Central Contacts

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Andrea B Parker, MSc., PhD

Role: CONTACT

+1 289 910 0862

Heather Dalgleish, MSc.

Role: CONTACT

+1 289 910 0384

Facility Contacts

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Chadi Ayoub, MD

Role: primary

Amin Sabet, MD

Role: primary

Prajwal Reddy, MD

Role: primary

Prajwal Reddy, MD

Role: primary

Mohammed Al-Kazaz, MD

Role: primary

Luigi Adamo, MD

Role: primary

Syed Haider, MD

Role: primary

Jonathan Salik, MD

Role: primary

David Lin, MD

Role: primary

Sushil A Luis, MD

Role: primary

Michael Garshick, MD

Role: primary

Dor Lotan, MD

Role: primary

Dor Lotan, MD

Role: primary

Dennis Finkielstein, MD

Role: primary

Tom Wang, MD

Role: primary

Maan Malahfji, MD

Role: primary

Libo Wang, MD

Role: primary

Tracy Hagerty, MD

Role: primary

Antonio Abbate, MD

Role: primary

Georgia Thomas, MD

Role: primary

Vartan Mardigyan, MD

Role: primary

George Lazaros, MD

Role: primary

Antonio Brucato, MD

Role: primary

Alida Caforio, MD

Role: primary

Alessandro Andreis, MD

Role: primary

Valentino Collini, MD

Role: primary

References

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Imazio M, Klein AL, Brucato A, Abbate A, Arad M, Cremer PC, Insalaco A, LeWinter MM, Lewis BS, Lin D, Luis SA, Nicholls SJ, Sutej P, Wasserstrum Y, Clair J, Agarwal I, Wang S, Paolini JF; RHAPSODY Investigators. Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept. J Am Heart Assoc. 2024 Mar 19;13(6):e032516. doi: 10.1161/JAHA.123.032516. Epub 2024 Mar 12.

Reference Type BACKGROUND
PMID: 38471825 (View on PubMed)

M Imazio, L Trotta, E Bizzi, M Pancrazi, S Wang, J Clair, A L Klein, E Tombetti, A Brucato, J F Paolini, RHAPSODY Investigators, Multi-year recurrent pericarditis disease duration in Italian patients: clinical outcomes after cessation of long-term IL-1 pathway inhibition provide insights for chronic management, European Heart Journal, Volume 45, Issue Supplement_1, October 2024, ehae666.2104, https://doi.org/10.1093/eurheartj/ehae666.2104

Reference Type BACKGROUND

Other Identifiers

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Cardiol 100-006

Identifier Type: -

Identifier Source: org_study_id

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