AGILE (Early Phase Platform Trial for COVID-19)

Summary

The AGILE platform master protocol allows incorporation of a range of identified and yet-to-be-identified candidates as potential treatments for adults with COVID-19 into the trial. Candidates will be added into the trial via candidate-specific trial (CST) protocols of this master protocol as appendices. Having one master protocol ensures different candidates are evaluated in the same consistent manor and opening up new trials for new candidates is more efficient. Inclusion of new candidates will be based on pre-clinical data, evidence in the clinical setting and GMP capabilities.

Timeline

Start

2020-07-03

Primary completion

2027-03-31

Completion

2027-03-31

Publications

• Background Griffiths G, Fitzgerald R, Jaki T, Corkhill A, Marwood E, Reynolds H, Stanton L, Ewings S, Condie S, Wrixon E, Norton A, Radford M, Yeats S, Robertson J, Darby-Dowman R, Walker L, Khoo S; UK NIHR community. AGILE-ACCORD: 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 structured summary of a study protocol for a randomised platform trial. Trials. 2020 Jun 19;21(1):544. doi: 10.1186/s13063-020-04473-1.
• Background Griffiths GO, FitzGerald R, Jaki T, Corkhill A, Reynolds H, Ewings S, Condie S, Tilt E, Johnson L, Radford M, Simpson C, Saunders G, Yeats S, Mozgunov P, Tansley-Hancock O, Martin K, Downs N, Eberhart I, Martin JWB, Goncalves C, Song A, Fletcher T, Byrne K, Lalloo DG, Owen A, Jacobs M, Walker L, Lyon R, Woods C, Gibney J, Chiong J, Chandiwana N, Jacob S, Lamorde M, Orrell C, Pirmohamed M, Khoo S; AGILE investigators. AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter. Trials. 2021 Jul 26;22(1):487. doi: 10.1186/s13063-021-05458-4.
• Results Khoo SH, Fitzgerald R, Fletcher T, Ewings S, Jaki T, Lyon R, Downs N, Walker L, Tansley-Hancock O, Greenhalf W, Woods C, Reynolds H, Marwood E, Mozgunov P, Adams E, Bullock K, Holman W, Bula MD, Gibney JL, Saunders G, Corkhill A, Hale C, Thorne K, Chiong J, Condie S, Pertinez H, Painter W, Wrixon E, Johnson L, Yeats S, Mallard K, Radford M, Fines K, Shaw V, Owen A, Lalloo DG, Jacobs M, Griffiths G. Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study. J Antimicrob Chemother. 2021 Nov 12;76(12):3286-3295. doi: 10.1093/jac/dkab318.
• Results Walker LE, FitzGerald R, Saunders G, Lyon R, Fisher M, Martin K, Eberhart I, Woods C, Ewings S, Hale C, Rajoli RKR, Else L, Dilly-Penchala S, Amara A, Lalloo DG, Jacobs M, Pertinez H, Hatchard P, Waugh R, Lawrence M, Johnson L, Fines K, Reynolds H, Rowland T, Crook R, Okenyi E, Byrne K, Mozgunov P, Jaki T, Khoo S, Owen A, Griffiths G, Fletcher TE; AGILE platform. An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2. Clin Pharmacol Ther. 2022 Mar;111(3):585-594. doi: 10.1002/cpt.2463. Epub 2021 Nov 13.
• Results Khoo SH, FitzGerald R, Saunders G, Middleton C, Ahmad S, Edwards CJ, Hadjiyiannakis D, Walker L, Lyon R, Shaw V, Mozgunov P, Periselneris J, Woods C, Bullock K, Hale C, Reynolds H, Downs N, Ewings S, Buadi A, Cameron D, Edwards T, Knox E, Donovan-Banfield I, Greenhalf W, Chiong J, Lavelle-Langham L, Jacobs M, Northey J, Painter W, Holman W, Lalloo DG, Tetlow M, Hiscox JA, Jaki T, Fletcher T, Griffiths G; AGILE CST-2 Study Group. Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Infect Dis. 2023 Feb;23(2):183-195. doi: 10.1016/S1473-3099(22)00644-2. Epub 2022 Oct 19.
• Results FitzGerald R, Dickinson L, Else L, Fletcher T, Hale C, Amara A, Walker L, Penchala SD, Lyon R, Shaw V, Greenhalf W, Bullock K, Lavelle-Langham L, Reynolds H, Painter W, Holman W, Ewings S, Griffiths G, Khoo S. Pharmacokinetics of ss-d-N4-Hydroxycytidine, the Parent Nucleoside of Prodrug Molnupiravir, in Nonplasma Compartments of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Clin Infect Dis. 2022 Aug 24;75(1):e525-e528. doi: 10.1093/cid/ciac199.
• Results Donovan-Banfield I, Penrice-Randal R, Goldswain H, Rzeszutek AM, Pilgrim J, Bullock K, Saunders G, Northey J, Dong X, Ryan Y, Reynolds H, Tetlow M, Walker LE, FitzGerald R, Hale C, Lyon R, Woods C, Ahmad S, Hadjiyiannakis D, Periselneris J, Knox E, Middleton C, Lavelle-Langham L, Shaw V, Greenhalf W, Edwards T, Lalloo DG, Edwards CJ, Darby AC, Carroll MW, Griffiths G, Khoo SH, Hiscox JA, Fletcher T. Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial. Nat Commun. 2022 Nov 26;13(1):7284. doi: 10.1038/s41467-022-34839-9.
• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

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Indications