IMpAct of CardiolRxTM oVer 6 months following IL-1 Blocker cessation in pERICarditis patients – MAVERIC: A randomized, double-blind, placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cardiol Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Cardiol Therapeutics Inc.

External identifiers

EU CT number

2024-517688-21-00

ClinicalTrials.gov

NCT06708299

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

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.
The primary safety objective is to demonstrate that administration of CardiolRx in the proposed doses in this patient population is safe and well tolerated.

Secondary objectives 1

1. The secondary efficacy objective is to assess whether CardiolRx can prolong periods with no or minimal pain.

Conditions and MedDRA coding

Recurrent Pericarditis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female 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. *Documented history of recurrent pericarditis is defined as a prior recurrent pericarditis episode with pericarditic chest pain AND elevated CRP ≥ 1.0 mg/dL.
3. Pericarditis pain ≤ 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). **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.
5. 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.
6. 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 20

1. Pericarditis recurrence(s) during IL-1 blocker treatment without interruption or tapering of the IL-1 blocker
2. 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)
3. 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
4. Inability or unwillingness to give informed consent
5. Ongoing drug or alcohol abuse in the opinion of the investigator
6. On any cannabinoid during the past month or unwilling to stay abstinent from all cannabis products for the duration of the trial
7. Pregnant or breastfeeding
8. Current diagnosis of active cancer, with the exception of non-melanoma skin cancer
9. Any factor, which would make it unlikely that the patient can comply with the trial procedures
10. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
11. 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)
12. 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)
13. Primary diagnosis of myocarditis (diagnosis of myopericarditis is accepted)
14. Estimated glomerular filtration rate (eGFR) < 30 mL/min during screening within 7 days prior to randomization (Visit 1, Day 1)
15. 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).
16. Sepsis, defined as documented bacteremia during screening within 7 days prior to randomization (Visit 1, Day 1) or other untreated or uncontrolled bacterial infection*
17. Prior history of sustained ventricular arrhythmia(s)
18. History of diagnosed long QT syndrome
19. 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)
20. Known hypersensitivity to the active substance or any of the excipients of the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The primary efficacy endpoint is the proportion of patients free from a new episode of recurrent pericarditis*, from the timepoint of stopping the IL-1 blocker to Visit 9 (Week 24).
2. * For the purpose of this trial, pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis (at least 1 day with pericarditis pain measurement ≥ 4 on the 11-point NRS AND a CRP value ≥ 1 mg/dL either on the same day or separated by no more than 7 days.
3. Safety parameters include the number of AEs and SAEs, changes in C-SSRS and in laboratory parameters, including liver function parameters and INR, as well as ECG intervals and rhythm during the trial period. In addition, all patients will have Pharmocokinetic (PK) samples obtained according to the Schedule of Trial Procedures (see Section 20.2).

Secondary endpoints 2

1. Exploratory efficacy endpoints include: - the restricted mean time to a new episode of pericarditis recurrence from the timepoint of stopping the IL-1 blocker to Visit 9 (Week 24) - the mean pain score using an 11-point NRS at Visit 6 (Week 8) and at Visit 9 (Week 24) (highest pain score recorded during the 7 days prior to Visit 6 and Visit 9) - the change in CRP from Visit 1 (Day 1) to Visit 6 (Week 8) and Visit 9 (Week 24), as measured by the central laboratory.
2. The secondary efficacy endpoint is the percentage of days with no or minimal pericarditis pain as assessed by an NRS score ≤ 2 from the timepoint of stopping the IL-1 blocker to Visit 9 (Week 24).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cardiol Therapeutics Inc.

Sponsor organisation

Cardiol Therapeutics Inc.

Address

2265 Upper Middle Road East Suite 602

City

Oakville

Postcode

L6H 0G5

Country

Canada

Scientific contact point

Organisation

Cardiol Therapeutics Inc.

Contact name

Corporate inquiries

Public contact point

Organisation

Cardiol Therapeutics Inc.

Contact name

Corporate inquiries

Third parties 7

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications