Phase II Trial to Evaluate Prevention of Infection with Mycobacterium tuberculosis of H56:IC31, a novel TB vaccine, in Tanzanian Adolescents

Dette forskningssamarbeidet har bakgrunn fra tidligere GLOBVAC-finansierte prosjekter med relevans for utvikling av vaksiner mot tuberkulose (TB). Partnere hadde søkt å gjennomføre en fase II vaksine-studie med en ledende vaksine-kandidat, H56:IC31 (SSI), i en ungdoms-kohort i høyendemiske land (Tanzania og sør Afrika). H56:IC31-vaksine studien var støttet av Forskningsråd (NFR-Globvac), Wellcome Trust og EDCTP. Målet med den planlagte fase II studien var å undersøke H56:IC31-vaksinens evne til å beskytte ungdoms-kohorten mot TB infeksjon. Dette er betraktet som en avgjørende egenskap for vaksine-kandidatens evne til å begrense TB epidemien i høyendemiske områder siden utvikling av smittsom TB skjer i 5-10% av personer med TB infeksjon. Partnere søkte GLOBVAC programstyret om en større vitenskapelig endring i august 2018. Årsaken var at nye resultater fra partnere fra vaksine forsøk i Sør-Afrika med H56:IC31s søster vaksine:H4, viste at studien, slik den var planlagt ikke var optimal. Søknaden ble behandlet av programstyret i GLOBVAC i september 2018. Styret konkluderte med at de omsøkte endringene i prosjektet er så omfattende at studien man nå ønsker å gjennomføre er vesentlig forskjellig fra studien som styret bevilget midler til i 2015. På bakgrunn av dette avslo de søknaden og konkluderte med at prosjektet avsluttes

Please refer to the detailed report that is attached.

This collaboration builds on GLOBVAC studies in tuberculosis (TB) vaccine development to conduct a phase II trial of one of the leading TB vaccine candidates (H56:IC31) in adolescents from a highly TB-endemic region. This vaccine has already proven effective against both primary and latent infection in non-human primate models, and safe and immunogenic in multiple human trials. It is the only vaccine in clinical trials with demonstrated effect against latent disease, a crucial point for vaccination in TB-endemic areas. As recommended by international experts and funding bodies, we will also include a strong biomarker component to identify markers associated with protection and response to vaccination. To deliver these goals, the planned phase II trial will use a new study design, with prevention of infection as an endpoint. The high attack rate of infection, compared to clinical disease means that it will be feasible to collect initial efficacy data even at phase II, and proof of concept is provided by data from BCG vaccination studies indicating that vaccination can reduce infection as well as disease. The effective use of multiplex PCR and intracellular flow cytometry for analysis of immune responses in the phase I trials conducted in the earlier GLOBVAC funded TB trials project will be expanded in the proposed study by 1) a greatly expanded panel of new genes, based on results from the last 4 years, 2) a growth inhibition assay that should provide information on the ability of the immune system to kill M. tuberculosis and 3) a new interferon-gamma response assay developed by one of the partners that offers hope of an improved point of care diagnostic. The consortium planning this work includes three Norwegian research groups, three Danish groups and partners from the US, and Tanzania. All have worked together before, have experience conducting clinical trials, and in addition bring new technology and millions of kroner in co-funding to the project.