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

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dc.contributor.authorGriffiths, Gareth O
dc.contributor.authorFitzGerald, Richard
dc.contributor.authorJaki, Thomas
dc.contributor.authorCorkhill, Andrea
dc.contributor.authorReynolds, Helen
dc.contributor.authorEwings, Sean
dc.contributor.authorCondie, Susannah
dc.contributor.authorTilt, Emma
dc.contributor.authorJohnson, Lucy
dc.contributor.authorRadford, Mike
dc.contributor.authorSimpson, Catherine
dc.contributor.authorSaunders, Geoffrey
dc.contributor.authorYeats, Sara
dc.contributor.authorMozgunov, Pavel
dc.contributor.authorTansley-Hancock, Olana
dc.contributor.authorMartin, Karen
dc.contributor.authorDowns, Nichola
dc.contributor.authorEberhart, Izabela
dc.contributor.authorMartin, Jonathan W B
dc.contributor.authorGoncalves, Cristiana
dc.contributor.authorSong, Anna
dc.contributor.authorFletcher, Tom
dc.contributor.authorByrne, Kelly
dc.contributor.authorLalloo, David G
dc.contributor.authorOwen, Andrew
dc.contributor.authorJacobs, Michael
dc.contributor.authorWalker, Lauren
dc.contributor.authorLyon, Rebecca
dc.contributor.authorWoods, Christie
dc.contributor.authorGibney, Jennifer
dc.contributor.authorChiong, Justin
dc.contributor.authorChandiwana, Nomathemba
dc.contributor.authorJacob, Shevin
dc.contributor.authorLamorde, Mohammed
dc.contributor.authorOrrell, Catherine
dc.contributor.authorPirmohamed, Munir
dc.contributor.authorKhoo, Saye
dc.date.accessioned2021-10-11T08:45:25Z
dc.date.available2021-10-11T08:45:25Z
dc.date.issued2021-07-26
dc.date.updated2021-08-01T03:14:54Z
dc.description.abstractBackground There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/design AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol 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 information is detailed in each candidate specific trial protocol of the master protocol. Discussion Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registration EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183  19 February 2021 ISRCTN reference: 27106947en_US
dc.identifier.apacitationGriffiths, G. O., FitzGerald, R., Jaki, T., Corkhill, A., Reynolds, H., Ewings, S., ... Khoo, S. (2021). 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. <i>Trials</i>, 22(1), 487. http://hdl.handle.net/11427/35143en_ZA
dc.identifier.chicagocitationGriffiths, Gareth O, Richard FitzGerald, Thomas Jaki, Andrea Corkhill, Helen Reynolds, Sean Ewings, Susannah Condie, et al "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." <i>Trials</i> 22, 1. (2021): 487. http://hdl.handle.net/11427/35143en_ZA
dc.identifier.citationGriffiths, G.O., FitzGerald, R., Jaki, T., Corkhill, A., Reynolds, H., Ewings, S., Condie, S. & Tilt, E. et al. 2021. 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. <i>Trials.</i> 22(1):487. http://hdl.handle.net/11427/35143en_ZA
dc.identifier.ris TY - Journal Article AU - Griffiths, Gareth O AU - FitzGerald, Richard AU - Jaki, Thomas AU - Corkhill, Andrea AU - Reynolds, Helen AU - Ewings, Sean AU - Condie, Susannah AU - Tilt, Emma AU - Johnson, Lucy AU - Radford, Mike AU - Simpson, Catherine AU - Saunders, Geoffrey AU - Yeats, Sara AU - Mozgunov, Pavel AU - Tansley-Hancock, Olana AU - Martin, Karen AU - Downs, Nichola AU - Eberhart, Izabela AU - Martin, Jonathan W B AU - Goncalves, Cristiana AU - Song, Anna AU - Fletcher, Tom AU - Byrne, Kelly AU - Lalloo, David G AU - Owen, Andrew AU - Jacobs, Michael AU - Walker, Lauren AU - Lyon, Rebecca AU - Woods, Christie AU - Gibney, Jennifer AU - Chiong, Justin AU - Chandiwana, Nomathemba AU - Jacob, Shevin AU - Lamorde, Mohammed AU - Orrell, Catherine AU - Pirmohamed, Munir AU - Khoo, Saye AB - Background There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/design AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol 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 information is detailed in each candidate specific trial protocol of the master protocol. Discussion Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registration EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183  19 February 2021 ISRCTN reference: 27106947 DA - 2021-07-26 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Trials KW - COVID-19 KW - SARS-CoV-2 KW - Randomised controlled trial KW - Platform study KW - Master protocol KW - Phase I/II, Bayesian LK - https://open.uct.ac.za PY - 2021 T1 - 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 TI - 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 UR - http://hdl.handle.net/11427/35143 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s13063-021-05458-4
dc.identifier.urihttp://hdl.handle.net/11427/35143
dc.identifier.vancouvercitationGriffiths GO, FitzGerald R, Jaki T, Corkhill A, Reynolds H, Ewings S, et al. 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;22(1):487. http://hdl.handle.net/11427/35143.en_ZA
dc.language.isoenen_US
dc.language.rfc3066en
dc.publisher.departmentDesmond Tutu HIV Centreen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceTrialsen_US
dc.source.journalissue1en_US
dc.source.journalvolume22en_US
dc.source.pagination487en_US
dc.source.urihttps://trialsjournal.biomedcentral.com/
dc.subjectCOVID-19en_US
dc.subjectSARS-CoV-2en_US
dc.subjectRandomised controlled trialen_US
dc.subjectPlatform studyen_US
dc.subjectMaster protocolen_US
dc.subjectPhase I/II, Bayesianen_US
dc.titleAGILE: 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 letteren_US
dc.typeJournal Articleen_US
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