Impact of CardiolRxTM on Recurrent Pericarditis
Primary Purpose
Recurrent Pericarditis
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CardiolRx
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Pericarditis
Eligibility Criteria
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)
- Has received non-steroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids (in any combination) in stable doses for at least 3 days prior to enrolment
- 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
- 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 presentation or other documented active infection
- 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
- Body weight > 170 kg
- Showing suicidal tendency as per the Columbia Suicide Severity Rating Scale (C-SSRS), administered at screening
On immunosuppressive therapy with any of the following:
- Rilonacept
- Anakinra
- Canakinumab
- Methotrexate
- Azathioprine
- Cyclosporine
- Intravenous immune globulin (IVIG)
Sites / Locations
- Pima Heart and Vascular Clinical ResearchRecruiting
- MedStar Health Research InstituteRecruiting
- Minneapolis Heart Institute FoundationRecruiting
- Mayo ClinicRecruiting
- Cleveland ClinicRecruiting
- University of Vermont Medical CenterRecruiting
- Virginia Commonwealth University HealthRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CardiolRx
Arm Description
pharmaceutically produced Cannabidiol
Outcomes
Primary Outcome Measures
11-point NRS pain score
change in patient-reported pericarditis pain using an 11-point NRS from baseline to 8 weeks
Secondary Outcome Measures
11-point NRS pain score
Pain score using 11-point NRS after 26 weeks of treatment
Normalized CRP levels
Percentage of patients with normalized CRP levels at 26 weeks (for patients with CRP ≥1.0 mg/dL at baseline)
Normalized CRP levels
Time to CRP normalization for patients with CRP ≥1.0 mg/dL at baseline
CRP change from baseline
CRP change from baseline
pericarditis recurrence during the extension period (EP)
Percentage of patients with pericarditis recurrence during the extension period (EP)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05494788
Brief Title
Impact of CardiolRxTM on Recurrent Pericarditis
Official Title
Impact of CardiolRxTM on Recurrent Pericarditis An Open Label Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cardiol Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Pericarditis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open label
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CardiolRx
Arm Type
Experimental
Arm Description
pharmaceutically produced Cannabidiol
Intervention Type
Drug
Intervention Name(s)
CardiolRx
Intervention Description
Pharmaceutically produced Cannabidiol
Primary Outcome Measure Information:
Title
11-point NRS pain score
Description
change in patient-reported pericarditis pain using an 11-point NRS from baseline to 8 weeks
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
11-point NRS pain score
Description
Pain score using 11-point NRS after 26 weeks of treatment
Time Frame
26 weeks
Title
Normalized CRP levels
Description
Percentage of patients with normalized CRP levels at 26 weeks (for patients with CRP ≥1.0 mg/dL at baseline)
Time Frame
26 weeks
Title
Normalized CRP levels
Description
Time to CRP normalization for patients with CRP ≥1.0 mg/dL at baseline
Time Frame
Over 26 weeks
Title
CRP change from baseline
Description
CRP change from baseline
Time Frame
26 weeks
Title
pericarditis recurrence during the extension period (EP)
Description
Percentage of patients with pericarditis recurrence during the extension period (EP)
Time Frame
26 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea B Parker, PhD
Phone
+1 289 9100862
Email
andrea.parker@cardiolrx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Andrew Hamer, MD
Email
andrew.hamer@cardiolrx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allen Klein, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Pima Heart and Vascular Clinical Research
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Waggoner
Email
tom.waggoner@pimaheart.com
Facility Name
MedStar Health Research Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Syed Haider
Email
syed.w.haider@medstar.net
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Lin
Email
David.Lin@allina.com
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S. A. Luis, MD
Email
luis.s@mayo.edu
First Name & Middle Initial & Last Name & Degree
S. A. Luis, MD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sonya Mihalus, BSN
Email
MIHALUS@ccf.org
First Name & Middle Initial & Last Name & Degree
Paul Cremer, MD
Facility Name
University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tracy Hagerty
Email
Tracy.Hagerty@uvmhealth.org
Facility Name
Virginia Commonwealth University Health
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georgia Thomas
Email
georgia.thomas@vcuhealth.org
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
26320112
Citation
Adler Y, Charron P, Imazio M, Badano L, Baron-Esquivias G, Bogaert J, Brucato A, Gueret P, Klingel K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristic AD, Sabate Tenas M, Seferovic P, Swedberg K, Tomkowski W; ESC Scientific Document Group. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015 Nov 7;36(42):2921-2964. doi: 10.1093/eurheartj/ehv318. Epub 2015 Aug 29. No abstract available.
Results Reference
background
PubMed Identifier
33200890
Citation
Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, Insalaco A, LeWinter M, Lewis BS, Lin D, Luis SA, Nicholls SJ, Pano A, Wheeler A, Paolini JF; RHAPSODY Investigators. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med. 2021 Jan 7;384(1):31-41. doi: 10.1056/NEJMoa2027892. Epub 2020 Nov 16.
Results Reference
background
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Impact of CardiolRxTM on Recurrent Pericarditis
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