Recurrent Pericarditis
Conditions
Brief summary
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
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.
Interventions
DRUGCardiolRx
Oral solution
Sponsors
Cardiol Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female 18 years of age or older 2. Diagnosis of at least two episodes of recurrent pericarditis\*, 3. At least 1 day with pericarditis pain ≥4 on the 11-point Numerical Rating Scale (NRS) within prior 7 days 4. One of; 1. C-Reactive Protein\*\* (CRP) level ≥1.0 mg/dL within prior 7 days OR 2. Evidence of pericardial inflammation assessed by delayed pericardial hyperenhancement on cardiac magnetic resonance imaging (CMR) 5. Currently receiving non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids (in any combination) for treatment of pericarditis in stable doses 6. 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. 7. 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: 1. Pericarditic chest pain 2. Pericardial rub 3. New widespread ST-segment elevation or PR-segment depression according to electrocardiogram (ECG) findings 4. Pericardial effusion (new or worsening) * Conversion: 1 mg/dL CRP = 10 mg/L hs-CRP
Exclusion criteria
1. 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 2. Estimated glomerular filtration rate (eGFR) \<30 mL/min at screening 3. 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 4. Sepsis, defined as documented bacteremia at the time of screening or other documented active infection 5. Prior history of sustained ventricular arrhythmia 6. History of QT interval prolongation 7. QTc interval \> 500 msec 8. Current participation in any research study involving investigational drugs or device 9. Inability or unwillingness to give informed consent 10. Ongoing drug or alcohol abuse 11. On any cannabinoid during the past month 12. Women who are pregnant or breastfeeding 13. Current diagnosis of cancer, with the exception of non-melanoma skin cancer 14. Any factor, which would make it unlikely that the patient can comply with the study procedures 15. Showing suicidal tendency as per the Columbia Suicide Severity Rating Scale (C-SSRS), administered at screening 16. On digoxin and/or type 1 or 3 antiarrhythmics 17. On immunosuppressive therapy with any of the following: 1. Rilonacept 2. Anakinra 3. Canakinumab 4. Methotrexate 5. Azathioprine 6. Cyclosporine 7. Intravenous immune globulin (IVIG)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 11-point NRS Pain Score | 8 weeks | Change in pain score from baseline using 11-point NRS after 8 weeks of treatment. Nominal Rating Scale from 0 to 10, where 0 represents no pain and 10 maximum pain. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pericarditis Recurrence During the Extension Period (EP) | 18 weeks | Percentage of patients with pericarditis recurrence during the extension period (EP) |
| CRP Change From Baseline | 26 weeks | CRP change from baseline, as measured locally at baseline and at weeks 8, 16, and 26. |
| Percentage of Patients With Normalized CRP Levels | 26 weeks | Percentage of patients with normalized CRP levels at 26 weeks (for patients with CRP ≥ 1.0 mg/dL at baseline) |
| Time to Normalized CRP Levels | Over 26 weeks | Time to CRP normalization for patients with CRP ≥1.0 mg/dL at baseline |
| 11-point NRS Pain Score | 26 weeks | Change in pain score from baseline using 11-point NRS after 26 weeks of treatment. Nominal Rating Scale from 0 to 10, where 0 represents no pain and 10 maximum pain. |
Countries
United States
Participant flow
Recruitment details
First patient enrolled on January 9, 2023; Last patient last visit on September 6, 2024
Pre-assignment details
8-week follow up; 18-week extension period
Participants by arm
| Arm | Count |
|---|---|
| CardiolRx pharmaceutically produced Cannabidiol
CardiolRx: Pharmaceutically produced Cannabidiol | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Period | Adverse Event | 1 |
| Extension Period | Withdrawal by Subject | 1 |
| Initial Treatment Period | Adverse Event | 2 |
| Initial Treatment Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | CardiolRx |
|---|---|
| Age, Continuous | 52.7 years STANDARD_DEVIATION 14.96 |
| CRP | 4.44 mg/dl STANDARD_DEVIATION 7.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| NRS Scores (Outcome measure 1) | 5.8 units on a scale STANDARD_DEVIATION 1.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 14 / 27 |
| serious Total, serious adverse events | 1 / 27 |
Outcome results
Primary
11-point NRS Pain Score
Change in pain score from baseline using 11-point NRS after 8 weeks of treatment. Nominal Rating Scale from 0 to 10, where 0 represents no pain and 10 maximum pain.
Time frame: 8 weeks
Population: All patients enrolled
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CardiolRx | 11-point NRS Pain Score | -3.7 units on a scale | Standard Deviation 2.07 |
Other Pre-specified
11-point NRS Pain Score
Change in pain score from baseline using 11-point NRS after 26 weeks of treatment. Nominal Rating Scale from 0 to 10, where 0 represents no pain and 10 maximum pain.
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CardiolRx | 11-point NRS Pain Score | 4.3 units on a scale | Standard Deviation 2.46 |
Other Pre-specified
CRP Change From Baseline
CRP change from baseline, as measured locally at baseline and at weeks 8, 16, and 26.
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CardiolRx | CRP Change From Baseline | 0.07 mg/dl | Standard Deviation 0.1 |
Other Pre-specified
Percentage of Patients With Normalized CRP Levels
Percentage of patients with normalized CRP levels at 26 weeks (for patients with CRP ≥ 1.0 mg/dL at baseline)
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CardiolRx | Percentage of Patients With Normalized CRP Levels | 7 Participants |
Other Pre-specified
Percentage of Patients With Normalized CRP Levels
Percentage of patients with normalized CRP levels at 8 weeks (for patients with CRP ≥1.0 mg/dL at baseline)
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CardiolRx | Percentage of Patients With Normalized CRP Levels | 7 Participants |
Other Pre-specified
Pericarditis Recurrence During the Extension Period (EP)
Percentage of patients with pericarditis recurrence during the extension period (EP)
Time frame: 18 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CardiolRx | Pericarditis Recurrence During the Extension Period (EP) | 7 Participants |
Other Pre-specified
Time to Normalized CRP Levels
Time to CRP normalization for patients with CRP ≥1.0 mg/dL at baseline
Time frame: Over 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CardiolRx | Time to Normalized CRP Levels | 26.4 days | Standard Deviation 18.46 |