Designing an adaptive phase II/III trial to evaluate efficacy, safety, and immune correlates of new TB vaccines in young adults and adolescents

Abstract

This article summarises the consensus arrived at during a meeting of South African and international stakeholders on specific late phase clinical trial design issues integrating the investigation of immune correlates as an integral part of a phase III protocol for a preventative TB vaccine in an adolescent/adult population. The challenge ahead is to optimize the planning for phase 3 TB vaccine preventative trials, under resource constraints, given that there are no known correlates of protection to shorten and increase the efficiencies of efficacy trials. An adaptive, multi-arm, group sequentially designed trial protocol is proposed incorporating design features that address uncertainties arising from both advances in the field and dynamic study populations and disease states. Such a design allows modifications that protect research subjects, save time, and maximize the impact of scarce financial resources. Further, the protocol underwent joint review by regulators from several African nations at a meeting of the African Vaccine Regulatory Forum (AVAREF), a regional regulatory harmonization initiative, and recommendations are included.

Citation

Rustomjee, R.; McClain, B.; Brennan, M.J.; McLeod, R.; Chetty-Makkan, C.M.; McShane, H.; Hanekom, W.; Steel, G.; Mahomed, H.; Ginsberg, A.M.; Shea, J.; Lockhart, S.; Self, S.; Churchyard, G.J. Designing an adaptive phase II/III trial to evaluate efficacy, safety and immune correlates of new TB vaccines in young adults and adolescents. Tuberculosis (2013) 93 (2) 136-142. [DOI: 10.1016/j.tube.2012.11.005]

Designing an adaptive phase II/III trial to evaluate efficacy, safety, and immune correlates of new TB vaccines in young adults and adolescents

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