AGILE (Early Phase Platform Trial for COVID-19)

AGILE is a multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II Bayesian randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19. This study allows for the assessment of many candidates at different doses, with the ability to add candidates as they are identified or drop them as their evaluation is completed. Promising candidates will move to an external trial for further evaluation in the phase II/III setting. Each candidate will be evaluated in its own trial, randomising between candidate and control with 2:1 allocation in favour of the candidate. Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol (as has been explained above) can be adapted for each candidate based on prior knowledge of the candidate - i.e. population, primary endpoint and sample size can be amended. This will be detailed in each candidate-specific trial protocol of the master protocol. Candidate-Specific Trial 2 (CST-2): Open-label 2:1 randomised controlled phase I of EIDD-2801 versus standard of care followed by a 1:1 blinded controlled parallel group Phase II trial of EIDD-2801 versus placebo. A phase I will be carried out to confirm the optimal dose in this group. Following a safety review, EIDD-2801 will be tested for efficacy in a blinded placebo controlled randomised phase II trial. Candidate-Specific Trial 3 (CST-3A): Multicentre, Adaptive, Phase I trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19 Candidate-Specific Trial 3 (CST-3B): A Randomized, Multicentre, Seamless, Adaptive, Phase I/II trial to Determine the optimal dose, Safety and Efficacy of Nitazoxanide for the Treatment of COVID-19 Candidate-Specific Trial 5 (CST-5): Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II dose of VIR-7832, and Evaluate the Safety and Efficacy of VIR-7831 and VIR-7832 for the Treatment of COVID-19 Candidate-Specific Trial 6 (CST-6): A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the Phase II dose and to Evaluate the Safety and Efficacy of intravenous Favipiravir for the Treatment of COVID-19 Candidate-Specific Trial 8 (CST-8): A Randomised, Multicentre, Seamless, Adaptive, Phase I Platform Study to Determine the recommended Phase II dose and Evaluate the Safety and Efficacy of antiviral combination of Molnupiravir and Paxlovid® for the Treatment of COVID-19 Candidate-Specific Trial 9 (CST-9a): A multicentre, adaptive Phase II Platform trial to evaluate the safety, efficacy and virological response of ALG-097558 as monotherapy and in combination with Remdesivir in high-risk population for the treatment of COVID-19 disease. Candidate-Specific Trial 9 (CST-9b): A Multicentre, Adaptive Phase II Randomised Double-Blind Placebo Controlled Trial to Evaluate the Safety, Efficacy and Virological response of ALG-097558 for the Treatment of COVID-19 disease.