A Phase 2, Randomized, Double-blind, Placebo-controlled Study of oral RP7214, a DHODH inhibitor, in Patients with Symptomatic Mild SARS-CoV-2 Infection

Introduction COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of immense global public health concern. RP7214, a novel, potent, oral, inhibitor of DHODH, has shown preclinical evidence in inhibiting viral replication and lung inflammation. Methods This was a randomized, double-blind, placebo-controlled phase 2 study in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., hypertension, diabetes mellitus) for developing severe Covid-19 infection. The patients received RP7214 (400 mg BID) or a placebo for 14 days in a blinded fashion and were followed up to 30 days. Patients also received supportive therapy (e.g., antipyretics and antitussives for symptomatic relief) at the discretion of the investigator. The endpoints were Covid 19 related hospitalization rate by Day 15, SARS-CoV-2 viral load and clearance on Days 3,7 and 15, clinical symptoms improvement by Day 15, safety, and the immuno-modulatory effect of RP7214. Results A total of 163 patients were treated in the study; 82 received RP7214 and 81 received placebo. Of the total patients, 44.2% had received Covid-19 vaccine prior to the study. The symptom onset was ≤ 3 days in 22.1%. None of the patients in the study required hospitalization. There was no difference in the mean change of viral load between RP7214 and placebo. In the subgroup analysis, in patients having symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Days 3 and 7, respectively. Similarly, in non-vaccinated patients with symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Day 3. Overall, there was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. For all other endpoints, there was no difference between RP7214 and placebo. Majority of the reported AEs were mild and not related either to study treatment. Conclusions RP7214 at 400 mg BID dose level showed a statistically significant reduction in viral load at an early stage of the disease and in non-vaccinated patients. There was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. RP7214 showed a favorable safety profile. Further development of RP7214 in Covid 19 in a mild symptomatic population with co-morbidities and treated at an early stage of disease may show benefit.