Outline of trial designs for experimental therapeutics

Overview

Among the different therapeutic options, Remdesivir was considered the most promising candidate based on the broad antiviral spectrum, the in vitro and in-vivo data available for coronaviruses and the extensive clinical safety database (in particular coming from the Ebola virus disease clinical trial and MEURI) in eastern Congo). Further, studies in mice using Remdesevir showed superior efficacy over Kaletra + IFNbeta. A clinical trial is being planned in China to evaluate the safety and efficacy of Remdesivir in association with optimized standard of care.

Among the repurposed drugs, the investigation of the antiretroviral medicine (HIV protease inhibitors), lopinavir/ritonavir, either alone or in combination with IFNbeta1b, which is a combination currently investigated in the Kingdom of Saudi Arabia for the treatment of MERS-CoV (MIRACLE trial), was considered a suitable second option for rapid implementation in clinical trials. Preclinical data available and limited clinical experience in the context of MERS, would suggest that it could provide some degree of clinical benefit and would be worth investigating particularly in severe cases. Based on the investigation conducted in Saudi Arabia (with mortality at day 90 as the endpoint), a protocol assessing lopinavir/ritonavir as monotherapy, is being implemented in China, with clinical improvement by day 28 as the endpoint. Recruitment of this trial is close to completion. Interim analysis outcomes are anticipated shortly.