Evaluation of Cannabidiol Efficacy in Maintaining Remission Post-IL-1 Blocker Withdrawal in Recurrent Pericarditis: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-517688-21-00
- Protocol
- 100-006
- Sponsor
- Cardiol Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate whether patients with **IL-1 blocker**-dependent recurrent **pericarditis** can successfully discontinue IL-1 blocker therapy and remain free of recurrence while receiving **CardiolRx**. This is clinically significant as it may offer a new therapeutic strategy for managing recurrent pericarditis, potentially reducing dependency on IL-1 blockers and their associated side effects. Additionally, the primary safety objective is to demonstrate that CardiolRx, administered in the proposed doses, is safe and well tolerated in this patient population.
The secondary efficacy objective is to assess whether CardiolRx reduces the time to pericarditis recurrence. This could provide further insights into the potential benefits of CardiolRx in prolonging the recurrence-free period in patients with recurrent pericarditis.
Participants
The clinical trial involves a total of **56 participants** diagnosed with **recurrent pericarditis**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a history of recurrent pericarditis with stable disease, currently managed with an IL-1 blocker, which is scheduled to be discontinued. The trial population was selected based on specific criteria, including stable treatment with an IL-1 blocker for at least 12 months and being free of pericarditis recurrence for at least 6 months. Participants must have a pericarditis pain score of 2 or less on the 11-point Numerical Rating Scale for the 7 days prior to the start of the trial and a C-Reactive Protein level of less than 1.0 mg/dL within the 7 days of screening. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to contraception requirements if applicable. The trial includes a vulnerable population, ensuring comprehensive safety and efficacy assessments of the investigational therapy, CardiolRx.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **CardiolRx**, a cannabidiol-based solution, in patients with recurrent pericarditis who are dependent on IL-1 blockers. This study is a **randomized, double-blind, placebo-controlled** trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, which is a non-aqueous solution of medium chain triglycerides with 1.0% vitamin E. The trial is set to last for a total duration of 24 weeks, with the estimated recruitment start date in April 2025 and an estimated end date in July 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, history of recurrent pericarditis, and current treatment status. Following randomization, participants will attend regular follow-up visits to monitor efficacy and safety parameters, including pain scores and C-Reactive Protein (CRP) levels. The primary efficacy endpoint is the proportion of patients free from a new episode of recurrent pericarditis from the cessation of the IL-1 blocker to Week 24. Safety will be assessed through the number of adverse events (AEs) and serious adverse events (SAEs), as well as changes in laboratory parameters and electrocardiogram (ECG) readings.
The expected length of participant involvement is approximately 6 months, with conditions for early termination including the occurrence of significant adverse events or failure to adhere to the study protocol. Participants will conclude their involvement with an end-of-study visit, where final assessments will be conducted to evaluate the overall outcomes of the trial. The study aims to provide valuable insights into the potential of CardiolRx as a treatment option for maintaining remission in patients with recurrent pericarditis following the discontinuation of IL-1 blockers.
Treatment
The clinical trial involves the administration of **CardiolRx**, an experimental medication formulated as a solution. The active substance in CardiolRx is **cannabidiol**, a chemical compound. The pharmaceutical form of CardiolRx is a solution, and it is administered orally. The dosing regimen for CardiolRx involves a maximum daily dose of 20 mg/kg, with a total maximum dose of 3255 mg/kg over the treatment period. The maximum treatment period is 24 weeks. The medication is produced by Cardiol Therapeutics Inc. and is classified as a synthetic pharmaceutical. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.
In addition to the experimental treatment, the study includes the use of a placebo, known as **CardiolRx Placebo**. This placebo is a non-aqueous solution composed of medium chain triglycerides with 1.0% vitamin E serving as an antioxidant. The CardiolRx Placebo is a pale yellow clear liquid and is designed to mimic the CardiolRx drug product, excluding the active drug substance, cannabidiol. The placebo is administered orally, following the same dosing schedule as the active treatment, to maintain the double-blind nature of the trial. The use of the placebo allows for the assessment of the efficacy and safety of CardiolRx in comparison to a non-active treatment.
Efficacy
Efficacy in this clinical trial will be assessed primarily by evaluating the proportion of patients who remain free from a new episode of recurrent **pericarditis** from the time of discontinuing the IL-1 blocker to Week 24. A recurrence of pericarditis is defined as the return of typical pericarditis pain, supported by objective evidence such as a pain measurement of 4 or higher on the 11-point Numerical Rating Scale (NRS) and a C-Reactive Protein (CRP) value of 1 mg/dL or more, either on the same day or within a 7-day interval.
Secondary efficacy endpoints include the median time to a new pericarditis recurrence from the cessation of the IL-1 blocker to Week 24. Exploratory efficacy endpoints will assess changes in pain scores using the 11-point NRS from baseline to Week 8 and Week 24, as well as changes in CRP levels from baseline to these same timepoints. These assessments will be conducted at specified visits, with baseline measurements taken during the 7 days prior to Day 1 and subsequent measurements at Week 8 and Week 24.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female 18 years of age or older
- 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. *Documented history of recurrent pericarditis is defined as a prior recurrent pericarditis episode with pericarditic chest pain AND elevated CRP ≥ 1.0 mg/dL.
- Pericarditis pain ≤ 2 on the 11-point Numerical Rating Scale (NRS) for at least 7 days prior to randomization (Visit 1, Day 1)
- C-Reactive Protein (CRP**) < 1.0 mg/dL during screening within 7 days prior to randomization (Visit 1, Day 1). **The term “CRP” will be used in this protocol for CRP and high-sensitivity CRP (hs-CRP) analyses performed at local laboratories for the evaluation of eligibility and suspected pericarditis recurrences. If available, hs-CRP is the preferred analysis method to be used.
- Male 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.
- WOCBP*** willing to use an acceptable method of contraception starting with trial therapy 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. 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
- Pericarditis recurrence(s) during IL-1 blocker treatment without interruption or tapering of the IL-1 blocker
- 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)
- 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
- Inability or unwillingness to give informed consent
- Ongoing drug or alcohol abuse in the opinion of the investigator
- On any cannabinoid during the past month or unwilling to stay abstinent from all cannabis products for the duration of the trial
- Pregnant or breastfeeding
- Current diagnosis of active cancer, with the exception of non-melanoma skin cancer
- Any factor, which would make it unlikely that the patient can comply with the trial procedures
- Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
- Has received systemic immunomodulatory agents as below prior to randomization: a. Methotrexate (within 2 weeks) b. Azathioprine, mycophenolate mofetil, cyclosporine, everolimus, tacrolimus, sirolimus, or mercaptopurine (within 24 weeks) c. Canakinumab, TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors (within 12 weeks) d. Intravenous immune globulin (IVIG) (within 8 weeks) e. Corticosteroids (within 4 weeks)
- 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)
- Primary diagnosis of myocarditis (diagnosis of myopericarditis is accepted)
- Estimated glomerular filtration rate (eGFR) < 30 mL/min during screening within 7 days prior to randomization (Visit 1, Day 1)
- 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).
- Sepsis, defined as documented bacteremia during screening within 7 days prior to randomization (Visit 1, Day 1) or other untreated or uncontrolled bacterial infection*
- Prior history of sustained ventricular arrhythmia(s)
- History of diagnosed long QT syndrome
- QTc interval > 480 msec (female) or > 470 msec (male) 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)
- Known hypersensitivity to the active substance or any of the excipients of the trial
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Recruiting | 30 Apr 2025 | 4 |
 Italy | Not Recruiting | 30 Apr 2025 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CardiolRx™ Placebo is a non-aqueous solution of medium chain triglycerides with 1.0% vitamin E as anti-oxidant. CardiolRx™ Placebo is a pale yellow clear liquid. The CardiolRx™ Placebo product is essentially the same as the CardiolRx™ drug product with the exception that the placebo does not include the active drug substance, cannabidiol. | Placebo | N/A | — | — | — | N/A |
CardiolRx | Test | SOLUTION | ORAL | 20 | 24 | PRD9565451 |