The project has progressed according to plan, with some delay. The study started in July 2017 and last patient out was in April 2019, 729 travellers have been vaccinated in Finland and travelled to Grand Popo in Benin to participate in the study. As the project is complex and includes organizations from several different countries, Scandinavian Biopharma invests a lot of effort into co-ordination, communication and dissemination activities. During the latter part of the study, there was some time delays: a) FIMEA the Finnish pharmaceutical agency conducted an audit that the project team successfully responded to b) The Finish CRO Medfiles had to change data management supplier in Finland at a very late stage c) The covid 19 pandemic in Finland caused a standstill in the close-out visits and the last reports of the study.
The project has attracted major media attention as well as scientific attention and World Health Organization is following the project closely.
The primary results confirm the excellent safety and overall positive immunogenicity of ETVAX®. While not reaching our protective efficacy goal of 70%, we are pleased to see a significant protective efficacy (PE = 56%) against all severe diarrhea, regardless of pathogen, most likely because ETEC was found in 75% of all severe diarrhea cases.
Despite the higher than expected TD attack rate and severity of ETEC-associated disease, ETVAX® provided significant protection. The PE against moderate-to-severe disease among vaccine responders (≥4-fold seroconversion to LTB) against any ETEC, and allowing for concomitant presence of EAEC, EPEC, EIEC/Shigella, Salmonella sp., Campylobacter sp., and parasites, was 52% (p=0.006; 95% CI=18-72%), representing 25% of all TD. When disregarding vaccine immune response, the protection remained significant (PE=41%, p=0.02; 95% CI=7-63%). Mixed infection with ETEC of another toxin and/or CF phenotype proved surprisingly common (18% of VPO ETEC cases) and decreased the measured protective capacity slightly. Overall, the PE against diarrhea of any cause (including viral pathogens) affecting daily activities increased progressively with increasing severity of disease, so that among vaccine responders with ≥16 loose stools in 24 hours the PE was 56% (p=0.025 CI= 9-83%) and disregarding the vaccine immune response it was 43% (p=0.05). This represents 22% of all TD.
