Objective
Drug development in TB requires new integrated methods to transition the novel combination regimens needed to shorten first-line therapy and combat multi-drug resistance. Although new agents are emerging, the path to registration of such regimens remains uncertain while capacity for pivotal trials is limited. Selection and optimization of drug combinations for development depends on preclinical systems which do not capture in vivo pharmacodynamics of heterogeneous states of M.tuberculosis.These systems are diverse and their predictive power for clinical trial outcomes is uncertain, escalating risks during development. To overcome these bottlenecks, PreDiCT-TB will take a comprehensive model based approach, synthesizing and integrating preclinical and clinical information. We will harness innovative technologies to develop an integrated set of predictive pre-clinical tools to facilitate selection of the best drug combinations and dosages for entry into optimized clinical studies. We will develop diverse existing and innovative experimental models of pharmacodynamics from extracellular MTB organisms, through to acute and chronic animal models in different species. We will enhance these systems using innovative single cell and functional imaging, novel mycobacteriological approaches and identification of biomarkers of lethality and sterilization. We will represent these critical data using multi-scale mathematical approaches incorporating PK-PD and disease models, supported by a translational data integration platform.The aim is an optimized decision pathway for combination regimens to progress to innovative early clinical trials. We will develop this modelling framework using a training set of reference compounds and subsequently update it with emerging data from new compounds. We believe that this comprehensive approach is the only way to overcome existing gaps in translation and create an effective and rapid drug development strategy for European researchers.
Fields of science
Topic(s)
Call for proposal
IMI-JU-03-2010
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Coordinator
28760 TRES CANTOS MADRID
Spain
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Participants (19)
L69 7ZX Liverpool
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28903 Getafe (Madrid)
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80539 Munchen
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3015 GD Rotterdam
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LS2 7UE Leeds
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75724 Paris
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SW17 0RE London
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KY16 9AJ St Andrews
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1015 Lausanne
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LE1 7RH Leicester
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WC1E 6BT London
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1081 HV Amsterdam
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NW1 0NH London
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2333 CH Leiden
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L35QA LIVERPOOL 3
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751 05 Uppsala
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94250 GENTILLY
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2340 Beerse
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BN1 9RH Brighton
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