Back to search

GLOBVAC-Global helse- og vaksin.forskn

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

Awarded: NOK 3.6 mill.

This collaboration was based on GLOBVAC studies in tuberculosis (TB) vaccine development and the plan was to conduct a phase II trial of one of the leading TB vaccine candidates (H56:IC31) in adolescents from highly TB-endemic regions (Tanzania and South Africa). The consortium that planned this study included two Norwegian research groups (Univ. of Bergen and Univ. of Oslo), three Danish groups (SSI, Univ. of Copenhagen, GSK Europe)and partners from the US (Aeras), Netherlands (Univ. of Leiden), and Tanzania (NIMR, Mwanza). The proposed phase II trial was funded by the Research Council of Norway (RCN-Globvac), Wellcome Trust and EDCTP2. At the time of the grant award in 2016, H56:IC31 had proven effective against both primary and latent infection in non-human primate models, and was shown to be safe and immunogenic in multiple human trials. The project also included a strong biomarker component to identify markers associated with protection and response to vaccination. To deliver these goals, the planned phase II trial was to use a new study design, with prevention of infection as an endpoint. The high attack rate of infection, compared to clinical disease would mean that it would 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. Apart from the funding awarded by the RCN for the conduct of the phase II trial in Mwanza, Tanzania, the consortium was successful in obtaining additional funding from Wellcome Trust (6th June 2017), which would support trial activities at an additional site i.e. the Aurum site in South Africa. In addition, the H56POI consortium also obtained (2017) EDCTP funding for a second back-up site (Welkome) in South Africa for the phase II TB vaccine trial as part of a risk mitigation strategy. In June 2018, partners from SSI, Denmark and Aeras, USA communicated their latest results from trials with the H56:IC31s sister vaccine: H4, both in a prevention of TB infection (POI) trial and in a head to head comparison with H56 (the vaccine to be used in GLOBVAC 248042). The results from these studies had implications for project no. 248042 and the POI trial could not conducted as earlier proposed. In August 2018 partners proposed instead an alternate H56:IC31 Phase 2a study which was not approved by the RCN board. As a consequence, the project was terminated in September 2018.

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.

Publications from Cristin

No publications found

No publications found

No publications found

No publications found

Funding scheme:

GLOBVAC-Global helse- og vaksin.forskn