A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in COVID-19 (PLATCOV)

PLATCOV is an ongoing phase 2, open label, randomised, controlled adaptive platform trial. It is unique in providing a standardised quantitative comparative method for in vivo assessment of potential antiviral treatments in low-risk adults with early symptomatic COVID-19. The primary outcome is the rate of viral clearance measured as the slope of the log10 oropharyngeal viral clearance curve over the first 7 days following randomisation. The treatment effect is the multiplicative change in viral clearance rate relative to the no study drug arm. PLATCOV has recruited over 550 patients and provided definitive assessments of ivermectin (no effect), remdesivir (42% acceleration in viral clearance), casivirimab/imdevimab (60% acceleration in Delta, and approximately 20% acceleration in Omicron BA.2 and BA.5). This proposal is to continue PLATCOV in order to assess new antiviral drugs and monoclonal antibodies and combinations, to extend to five study sites across the world (continue in Thailand and Brazil, add Pakistan, Laos and an African site), and to conduct preliminary evaluations of a similar pharmacometric design to assess anti-influenza drugs. The final objective is definitive assessments of comparative antiviral effects in COVID-19, and initial establishment of a global platform for pharmacometric assessment of interventions in pandemic respiratory infections.