Project: POR TB consortium; Phase 2 trial to determine efficacy of the multistage vaccine H56:IC31 for Prevention Of Recurrent TB disease

Acronym	POR TB (Reference Number: RIA2016V-1631)
Duration	01/11/2017 - 31/10/2022
Project Topic	The World Health Organisation has set the goal of ending the tuberculosis (TB) epidemic by 2035 and the United Nations (UN) has set a similar target within the Sustainable Development Goals of ending TB by 2030. The current tools used for controlling TB are ineffective and new solutions are desperately needed. The primary objective of this proposal is to unite six African and two European research institutions, clinical trial sites and vaccine developers in a consortium to conduct an innovative and cost-effective TB vaccine Phase 2b efficacy trial. The trial will use prevention of TB recurrence (POR) post-TB treatment as an indicator for the ability of a vaccine to prevent TB disease in the broader population. H56:IC31 is the lead TB vaccine candidate from Statens Serum Institut (SSI), based on a novel multistage vaccine concept targeting different stages of infection and is supported by a very extensive preclinical animal model data package to support both its preventive and unique therapeutic effect. H56:IC31 has been assessed in three completed and two ongoing human trials, providing supporting data that H56:IC31 is well tolerated and immunogenic in Mtb-infected individuals, in patients following cure of active TB, and in uninfected individuals. Our proposed POR trial comprises 900 participants with active TB, randomized to receive H56:IC31 or placebo after standard, successful six-month drug treatment, and monitored for recurrent TB for 12 months. Building on previous successful TB vaccine trial partnerships also supported under EDCTP, our Consortium’s second objective is to build capacity and enable technology transfer in immunology and TB vaccine trial conduct between sites, to support appropriate community engagement activities, and facilitate training, networking and experience sharing. Utilizing unique access to well characterized samples from the trial, the third objective is to apply an extensive exploratory immunogenicity package of analyses to explore the host transcriptome and immune responses to vaccine and infection, as well as bacterial genomes, for correlates of risk and/or protection, and to compile a comprehensive biobank with clinical samples for future studies. The consortium aims to accelerate TB vaccine development by evaluating a leading candidate in a novel proof-ofconcept trial design to facilitate early vaccine development decisions, undertaking capacity building, and enabling correlate of protection discovery, thereby laying the foundation for Phase 3 TB vaccine trials. Importantly, a successful POR vaccine may allow shortening of TB treatment regimens for drug resistant TB.
Network	EDCTP2
Call	Vaccines for poverty-related diseases (PRDs)

Project partner

Number	Name	Role	Country
1	Statens Serum Institut	Coordinator	Denmark
2	Aeras Global Tuberculosis Foundation NPC	Partner	South Africa
3	National Institute for Medical Research - Tanzania	Partner	Tanzania
4	Ospedale San Raffaele SRL	Partner	Italy
5	TASK Foundation NPC	Partner	South Africa
6	The Aurum Institute NPC	Partner	South Africa
7	University of Cape Town	Partner	South Africa
8	University of Cape Town Lung Institute (Pty) Ltd	Partner	South Africa