Study Protocol for a Randomized Double-blind Placebo-controlled Phase 2 Clinical Trial to Assess Anti-inflammatory Effect of Colchicine (DRC3633) in Mild to Moderately Severe COVID‒19 Patients (DRC-06C)

Introduction: Given that coronavirus disease 2019(COVID-19)aggravation is associated with an excessive host immune response, complementary anti-inflammatory treatment is recommended in severe disease. Although dexamethasone is a widely used anti-inflammatory agent in COVID-19 patients with respiratory failure, its use in patients with mild COVID-19 not receiving oxygen could have harmful effects. Colchicine, an anti-inflammatory drug, blocks the upstream immune response by inhibiting NALP3 inflammasome activation. This study aimed to assess the efficacy and safety of low-dose colchicine(DRC 3633)in mild COVID-19. Method(s): This study is a prospective, multicenter, placebo-controlled, double-blind randomized, phase 2 clinical trial patients with moderate COVID-19 admitted at nine hospitals in Japan (jRCT2071200078). The primary endpoint is area under the curve(AUC)for the amount of change of serum hypersensitive C-reactive protein(hs-CRP)from baseline to 1, 2, and 4 weeks after initiating investigational drug. Study participants will be randomly assigned to the colchicine or placebo group at a 1:1 ratio. On day 1, patients in the colchicine group will receive 1 mg of colchicine, followed by 0.5 mg of colchicine after 2 h barring gastrointestinal complications. From day 2 to 28, 0.5 mg of colchicine will be administered once daily. Discussion(s): An appropriate anti-inflammatory strategy is critical to improve the outcome of severe COVID-19 patients. This study will assess the efficacy of low-dose colchicine not only by the AUC of the amount of change in serum hs-CRP from baseline to several time points, but also by evaluating whether the result of the primary endpoint is consistent with other relevant biomarkers and clinical parameters measured as secondary endpoints. Copyright © 2022 the Japanese Society of Clinical Pharmacology and Therapeutics (JSCPT)