What is the Investigational Product in the Cardiol 100-002 Study?
CardiolRx™ is a pharmaceutically manufactured cannabidiol solution, formulated for oral administration. Cannabidiol is known to have anti-inflammatory properties.
Although the mechanisms of CardiolRx™’s anti-inflammatory effects are not fully understood, research suggests that the drug substance in CardiolRx™ attenuates multiple inflammatory signaling pathways, including inhibiting activation of the NLRP3 inflammasome.
Causes of acute myocarditis include viral or bacterial infection, therapies used to treat common cancers, mRNA vaccines, and systemic immune-mediated diseases, which lead to expression and activation of the NLRP3 inflammasome protein components that induce the release of pro-inflammatory cytokines (e.g., IL-1α, IL-1β, IL-6, & IL-18), thereby activating and recruiting leukocytes into the myocardium.
Excessive or persistent activation can lead to an exaggerated and/or chronic inflammatory response that triggers myocardial injury, remodeling, and fibrosis, culminating in deteriorating cardiac function, with potential progression to heart failure.
The drug substance in CardiolRx™ has been shown to significantly decrease the pro-inflammatory cytokines IL-1β and IL-6 and inhibit pro-IL-1β and NLRP3 mRNA expression in vitro, and cannabidiol has also bee shown to attenuate myocarditis-induced fibrosis in an animal model of experimental autoimmune myocarditis.
NLRP3 = NACHT, leucine-rich repeat, and pyrin domain-containing protein 3
Who is Eligible for the Study?
Key Inclusion Criteria:
- Male or female patients aged ≥18 years
- Diagnosed with acute myocarditis including:
- Clinical criteria (symptoms of chest pain, arrhythmia or shortness of breath, or history of viral-like illness), preferably followed by elevated troponin; PLUS,
- CMR diagnosis (Lake Louise Criteria) within 10 days prior to randomization; OR, endomyocardial biopsy showing either cellular inflammation and/or immunohistochemistry consistent with inflammation.
Key Exclusion Criteria:
- Coronary artery disease (CAD) defined as a stenosis greater than 50% in a major epicardial coronary artery
- Severe valvular heart disease
- Inability to safely undergo CMR including administration of gadolinium
- Documented biopsy evidence of giant cell or eosinophilic myocarditis
- Prior history of sustained ventricular arrhythmia
- Taken any cannabinoid in the past month
- Current diagnosis of cancer (except for non-melanoma skin cancer)
Additional eligibility criteria will be assessed by the study team during screening.
What is Expected of Study Participants?
The patient will review the detailed information about the study in an informed consent form (ICF) and provide written consent prior to the administration of any study-related assessments, procedures and treatment.
Participants must not take any prohibited concomitant medications during the study including:
- Digoxin and/or type 1 or 3 antiarrhythmics or strong inducers of CYP3A4 and CYP2C19
- Drugs that are known to prolong QTc intervals must not be started during the study
Participants are expected to attend scheduled study visits in clinic.
Frequently Asked Questions
Yes. A Phase 1 safety and pharmacokinetic study of single and multiple ascending doses of CardiolRx™ was completed and demonstrated that CardiolRx™ was safe and generally well tolerated at all dose levels, with no serious adverse events reported. In addition to the ARCHER study, CardiolRx™ is also being investigated in the MAvERIC-Pilot study to evaluate its safety and efficacy in patients with recurrent pericarditis (ClinicalTrials.gov Identifier: NCT05494788).
No. However, another form of cannabidiol oral solution (Epidiolex®) is FDA-approved and indicated for the treatment of seizures associated with certain epilepsy syndromes.
CardiolRx™ is pharmaceutically manufactured under Current Good Manufacturing Practice (cGMP), contains high-concentration (100 mg/mL) cannabidiol, and does not contain delta-9 THC (not detected at limit of detection 5 parts per million).
The study medication and all tests and procedures required by the study are provided at no cost to study participants. The costs of other medications, treatments, and procedures used independently of the ARCHER study are not covered by the Sponsor.
Participants will not be paid for being in this study, but will be reimbursed for reasonable expenses (e.g., travel, parking, meals) arising from outpatient visits.