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Project Topic
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TB is the most prominent cause of death from a single infectious agent globally and the standard vaccination with BCG is mostly efficient against severe forms of systemic TB, particularly TB meningitis and military disease. However, BCG provides only a limited protection against highly contagious pulmonary forms of TB and those are needed to be targeted by an efficient vaccination. Furthermore, the current shortages on BCG due to production difficulties and withdrawal of major manufacturers endanger global child health. Millions of people worldwide are under the risk of developing TB. Therefore, there is an urgent need to develop an alternative to BCG which is not only more effective but can also be produced in a way that meets the global demands in a reliable manner. VPM1002 is a BCG-derived vaccine, that is modified to be safer and more efficacious than BCG. Non-clinical and clinical studies already demonstrated that VPM1002 has a better safety profile than standard BCG. A phase II clinical trial in the target population of HIV-exposed and HIV-unexposed infants has recently completed recruitment in South Africa (416 infants recruited) and is investigating the safety and immunogenicity of VPM1002 in these infants. No vaccine-related serious adverse events have been registered to date. The proposed phase III trial aims to demonstrate the improved safety and efficacy of VPM1002 over BCG in prevention of Mtb infection. It is planned to recruit 6940 healthy male and female newborn infants in Sub-Saharan countries, who will be vaccinated with either VPM1002 or standard BCG. The primary objectives are to demonstrate that VPM1002 is non-inferior to and subsequently superior to BCG in providing protection against incident Mtb infection. While secondary objectives are to assess the safety and tolerability of VPM1002 and BCG, as well as their efficacy in terms of protection against TB disease, the exploratory endpoints will evaluate the immunological responses to VPM1002 or BCG in HIV-exposed vs. HIV-unexposed infants. Since the clinical sites in South Africa are well known to the team of VPM and SIIPL, only the non-South African sites, namely Kenya, Uganda, Tanzania and Gabon have been visited during the pre-study visits. Through the activities such as the pre-study visits, the consortium website, the kick-off meeting, and the financial reporting trainings, the interaction of the consortium partners has been strengthened. During the first reporting period the first milestone of the project has been reached. Scientific advice was taken from the German NRA, the Paul Ehrlich Institute (PEI) to determine and select the most meaningful endpoints for the trial that are required to assess the non-inferiorty and superiority of VPM1002 over BCG. After evaluating the valuable advices from the consortium partners and the PEI on the trial design, essential documents for the CTA started to being prepared by VPM and SIIPL. To finalize the CTP, VPM coordinated the preparation by VPM and SIIPL as well as the review of the document by all participating stakeholders. The clinical trial protocol is carefully prepared to safeguard the health and safety of the subjects. Concurrently, national and international guidelines were extensively investigated. The trial application packages for the NRAs and ethics committees are under preparation. After this pivotal phase III trial, the developers of VPM1002 will apply for market authorization to make this novel vaccine available to children in Sub-Saharan countries and worldwide. More information on the project can be found on our website: https://www.prime-vaccine.eu/.
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