Completed Cancer Infection & Immunity

AGILE: Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment

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AI plain-English summary

A new clinical trial platform called AGILE is now testing multiple experimental COVID-19 drugs in parallel, moving them from first-in-human use to finding the right dose for patients in a single, seamless process. Conventional drug trials are too slow for a pandemic. Each new medicine typically requires separate, sequential studies to establish safety and dosing before it can be tested for efficacy. AGILE replaces this stepwise approach with a single adaptive protocol that can evaluate several drug candidates at once, using small numbers of patients. The trial is designed to quickly eliminate drugs that are unlikely to work, and to funnel the most promising candidates into large-scale trials such as RECOVERY and SOLIDARITY. If AGILE succeeds, it could transform how rapidly new antiviral treatments reach patients during a pandemic. The platform is already approved by UK regulators and ethics bodies, and is recruiting COVID-19 patients in the community for early-stage testing of population-scalable antiviral drugs. The same adaptive design could be reused for future outbreaks, cutting months off the timeline from drug discovery to clinical evidence.

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Conventional evaluation of new medicines is not fast enough for a pandemic. Our aim is to accelerate this process, rapidly identifying which drugs are safe and potentially effective treatments for COVID-19. AGILE is an innovative, multi-arm, multi-dose, multi-stage Phase I/IIa Bayesian adaptive platform protocol to evaluate experimental COVID-19 therapies, and to funnel plausible candidates into large Phase IIb/III trials such as RECOVERY and SOLIDARITY. We will efficiently eliminate candidates with little or no prospect of clinical success. AGILE will recruit COVID-19 patients into very early phase clinical studies, including first-in-human. The innovative design allows us to move seamlessly from first-in-human use to finding the optimal dose for COVID-19 patients. The trial is pragmatic (requiring only small numbers of patients), adaptive (so that the right drug is tested in the right group of COVID-19 patients, either in the community or in hospital) and statistically efficient (so that several drugs can be tested in parallel, making best use of a small number of patients). Our primary focus is population-scalable antiviral drugs for early treatment of COVID-19, for which we will recruit primarily in the community. AGILE has full regulatory and ethics approvals in the UK

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Researchers

Andrew Owen (EPMC Awardee)Bella Starling (EPMC Awardee)David Lalloo (EPMC Awardee)Gareth Griffiths (EPMC Awardee)Michael Jacobs (EPMC Awardee)Mohammed Lamorde (EPMC Awardee)Munir Pirmohamed (EPMC Awardee)Richard FitzGerald (EPMC Awardee)Saye Khoo (EPMC Awardee)Shevin Jacob (EPMC Awardee)Thomas Fletcher (EPMC Awardee)Thomas Jaki (EPMC Awardee)William Greenhalf (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

POETIC-COVID: Provision Of Essential Treatment In Critical Illness in COVID-19
AGILE-ACCORD: ACelerating COVID-19 dRug Development - Phase I/II trial platform. A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19
A Randomised, Multicentre, Seamless, Adaptive Phase Ib/II Platform Trial to Determine the recommended Phase II dose and Evaluate the Safety and Efficacy of ALG-097558 as monotherapy and in combination with Remdesivir for the Treatment of mild-to-moderate COVID-19 disease
Agile CST-2: A Randomized, Multicentre, Seamless, Adaptive, Phase I/II Platform Study to Determine the optimal dose, Safety and Efficacy of EIDD-2801 (molnupiravir) for the Treatment of COVID-19
CANDIDATE SPECIFIC TRIAL PROTOCOL 8: Molnupiravir + Paxlovid® (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

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