Impact of CardiolRxTM on Recurrent Pericarditis

Study Overview
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Brief Summary
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Patients with recurrent pericarditis who are refractory or intolerant to current therapeutic management options or who require long-term administration of corticosteroids to control their disease are particularly challenging to manage. The pathogenesis of pericarditis involves the activation of the inflammasome. CardiolRxTM (a pure cannabidiol [CBD] solution) is known to have anti-inflammatory properties, including modulation of inflammasome signaling. This pilot study is to assess the tolerance and safety of CardiolRxTM during the resolution of pericarditis symptoms, assess improvement in objective measures of disease, and during the extension period, assess the feasibility of weaning concomitant background therapy including corticosteroids while taking CardiolRxTM.

Detailed Description
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Multi-center, open label Pilot Study. Patients who present with recurrent pericarditis will be screened and informed consent obtained. Baseline assessments include the following: Clinical assessment, including vital signs, highest NRS pain score within the past 7 days of Day 1, 12-lead ECG; C-SSRS as well as hematology and blood chemistry and a pregnancy test for women with child-bearing potential. Concomitant medications are recorded and any (S)AEs after informed consent has been obtained. Study treatment will be initiated in the evening of Day 1, after all baseline assessments are completed. Oral administration is as follows: Initial starting dose (Day 1 p.m. dose to Day 3 a.m. dose): 5 mg/kg of body weight CardiolRxTM Day 3 p.m. dose to Day 10 a.m. dose: 7.5 mg/kg of body weight CardiolRxTM b.i.d. Day 10 p.m. dose to end of treatment period: 10.0 mg/kg of body weight CardiolRxTM b.i.d. If the next higher dose after each study drug increase is not tolerated, the dose will be reduced to the previous tolerated dose. Unless contraindicated in the opinion of the investigator, after 8 weeks of treatment, patients will enter an 18-week extension period (EP), in which they continue study treatment while their concomitant medications will be weaned. Follow-up Procedures Every visit (before the next dose increase) the patient will be re-evaluated. This includes ECG monitoring at approximately 5 hours post-morning dose (Tmax) to surveil for deleterious effects on ECG intervals (particularly the QTc interval) and rhythm. Drug titration will be dependent on investigator or designate interrogation of the ECGs and the absence of new, clinically significant abnormalities on those ECGs. Vital signs, concurrent medication and (S)AEs will be recorded at all visits. Blood chemistry including liver function tests, hematology as well as INR assessments will be carried out at selected visits. Final efficacy assessments will take place after 26 weeks of study treatment and include a clinical assessment, vital signs, pain score NRS, a 12-lead ECG, the C-SSRS, as well as laboratory assessments. For patients who do not enter the EP, Final assessments will be done after 8 weeks.

Official Title
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Impact of CardiolRxTM on Recurrent Pericarditis An Open Label Pilot Study

Conditions
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Recurrent Pericarditis

Intervention / Treatment
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* Drug: CardiolRx


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 years of age or older Diagnosis of at least two episodes of recurrent pericarditis*, At least 1 day with pericarditis pain ≥4 on the 11-point Numerical Rating Scale (NRS) within prior 7 days One of; C-Reactive Protein** (CRP) level ≥1.0 mg/dL within prior 7 days OR Evidence of pericardial inflammation assessed by delayed pericardial hyperenhancement on cardiac magnetic resonance imaging (CMR) Currently receiving non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids (in any combination) for treatment of pericarditis in stable doses Male patients with partners of childbearing potential who have had a vasectomy or are willing to use double barrier contraception methods during the conduct of the study and for 2 months after the last dose of study drug. Women of childbearing potential willing to use an acceptable method of contraception starting with study drug administration and for a minimum of 2 months after study completion. Otherwise, women must be postmenopausal (at least 1 y absence of vaginal bleeding or spotting and confirmed by follicle stimulating hormone [FSH] ≥40 mIU/mL [or ≥ 40 IU/L] if less than 2 y postmenopausal) or be surgically sterile. Diagnosis of pericarditis according to the 2015 European Society of Cardiology (ESC) Guidelines for the Diagnosis and Management of Pericardial Diseases (Adler et al. 2015): At least two of: Pericarditic chest pain Pericardial rub New widespread ST-segment elevation or PR-segment depression according to electrocardiogram (ECG) findings Pericardial effusion (new or worsening) Conversion: 1 mg/dL CRP = 10 mg/L hs-CRP Exclusion Criteria: 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); myocarditis Estimated glomerular filtration rate (eGFR) <30 mL/min at screening 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 Sepsis, defined as documented bacteremia at the time of screening or other documented active infection Prior history of sustained ventricular arrhythmia History of QT interval prolongation QTc interval > 500 msec Current participation in any research study involving investigational drugs or device Inability or unwillingness to give informed consent Ongoing drug or alcohol abuse On any cannabinoid during the past month Women who are pregnant or breastfeeding Current diagnosis of cancer, with the exception of non-melanoma skin cancer Any factor, which would make it unlikely that the patient can comply with the study procedures Showing suicidal tendency as per the Columbia Suicide Severity Rating Scale (C-SSRS), administered at screening On digoxin and/or type 1 or 3 antiarrhythmics On immunosuppressive therapy with any of the following: Rilonacept Anakinra Canakinumab Methotrexate Azathioprine Cyclosporine Intravenous immune globulin (IVIG)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CardiolRx<br>pharmaceutically produced Cannabidiol | Drug: CardiolRx<br>* Pharmaceutically produced Cannabidiol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 11-point NRS pain score | change in patient-reported pericarditis pain using an 11-point NRS from baseline to 8 weeks | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 11-point NRS pain score | Pain score using 11-point NRS after 26 weeks of treatment | 26 weeks | 
| Normalized CRP levels | Percentage of patients with normalized CRP levels at 26 weeks (for patients with CRP ≥1.0 mg/dL at baseline) | 26 weeks | 
| Normalized CRP levels | Time to CRP normalization for patients with CRP ≥1.0 mg/dL at baseline | Over 26 weeks | 
| CRP change from baseline | CRP change from baseline | 26 weeks | 
| pericarditis recurrence during the extension period (EP) | Percentage of patients with pericarditis recurrence during the extension period (EP) | 26 weeks |