First-in-human study of EVT894, a monoclonal antibody against chikungunya virus exhibiting a long plasma half-life

Hugh Watson, Aarhus University

14:45 - 15:00 Tuesday 01 September Morning

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Abstract

Background: Outbreaks of chikungunya virus (CHIKV) infection continue to emerge in new regions, but currently there are no antiviral drugs for treatment or protection of susceptible individuals during a CHIKV outbreak. Following positive results in treatment and prophylaxis preclinical models, a fully human IgG1 anti-CHIKV monoclonal antibody (mAb), EVT894, was entered into clinical development. Methods: Healthy adults were enrolled in a randomized, double-blind, placebo-controlled, single dose escalation study (NCT04441905). Five dose levels of intravenous EVT894 were evaluated for safety, pharmacokinetics and immunogenicity. Doses administered were 0.3, 1, 3, 10 and 20 mg/kg. Each dose-cohort consisted of 8 subjects, randomized to EVT894 (n=6) or placebo (n=2), with a follow-up of 150 days for each subject. Results: No serious adverse event (AE), death or dose-limiting toxicity was reported during the study. AEs considered related to treatment were reported in 3 of 10 subjects on placebo and 2 of 30 subjects on EVT894, all mild in severity with no dose-related trend. Across the dose-levels tested, EVT894 half-life ranged from 56 to 99 days. Exposure increased with dose: Cmax was dose-proportional in this dose range, while AUC was slightly supra-proportional between the two first doses. No anti-drug antibodies were detected after EVT894 infusion. Conclusion: A single IV dose of EVT894 was generally safe and non-immunogenic in healthy adult participants in this study. The pharmacokinetic profile shows a mAb with a long half-life and potential for use both as treatment in acute CHIKV infection and as short to medium-term prophylaxis.

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