A Multicenter phase III double-blind; randomized; controlled study to evaluate the efficacy and safety of VPM1002 in comparison with BCG in HIV-exposed and HIV-unexposed

The aim of the development of VPM1002 is to replace BCG by a well-tolerated vaccine that has superior efficacy and a better safety profile. Pre-clinical as well as clinical data show that VPM1002 is safer and is more immunogenic than standard BCG treatment. A phase II clinical trial in the target population of HIV-exposed and is investigating the safety and immunogenicity of VPM 1002 in these infants. No vaccine-related serious adverse events have been registered. The proposed phase III trials plans to recruit 7,778 healthy male and female new-born infants, who will be vaccinated with either standard BCG or VPM1002 and followed up to 12 months on protocol.

The primary objectives of this study is to demonstrate superiority in terms of reduction in the combined incidence of efficacy-related (TB disease/disease due to infection with other virulent mycobacteria of the tuberculosis family) and safety related events (grade 3 and/or 4 adverse reactions, vaccine related lymphadenitis of 10 mm or greater (diameter) severe BCG disease) in infants vaccinated with VPM1002 compared with BCG after a follow up period of 12 months.

Secondary endpoints will explore the safety and efficacy parameters in HIV-exposed vs HIV-unexposed infants. As explorative endpoints, immunogenicity will be assessed by determining key immunological parameters, like multi-functional T cells by intracellular staining of cytokines, antibody production by B cells and transcriptome analysis of involved blood cells.

After this pivotal phase III trial, the developers of VPM1002 will apply foe market authorization in order to make this novel vaccine available to children in Sub-Saharan countries and worldwide. The manufacturing process of VPM1002 is streamlined and can be scaled up to meet the worldwide demand, which is in contrast to the current BCG manufactures.#