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Proposal 1224

Title of the Proposed Research


Lead Researcher

Gaston De Serres


Institut National de Santé Publique du Québec(INSPQ)
Laval University

Funding Source

Joseline Zafack will do this work as part of her PhD in Epidemiology for which she receives a scholarship of the CIRN network (Canadian Immunization Research Network) funded by the Canadian Institute of Health Research.

Potential Conflicts of Interest

Gaston De Serres received research grant from GSK and was reimbursed travel expenses to travel to an ad hoc advisory board meeting by GSK but received no honoraria.

Data Sharing Agreement Date

4 February 2016

Lay Summary

In 2014, Bexsero™ a four component serogroup B meningococcal vaccine (4CMenB) has been licensed in Europe, Canada, and Australia. It has also been used as an Investigational New Drug for outbreak control in the United States. The vaccination schedule of infants includes three visits at 2, 4 and 6 months of age for primary immunization and a booster dose at 12 months. To avoid additional visits, the doses of 4CMenB would ideally be administered concomitantly with routine vaccines. In infants under one year of age, prelicensure studies and post marketing surveillance data showed that 4CMenB has a high reactogenicity [1-4]. Pain at 4CMenB injection site occurs in 58-87% of vaccinees [1-3]. Fever (>=38°C) occurs in 71% in those who received 4CMenB alternatively with routine vaccines but in 76-80% of children who received 4CMenB concomitantly with routine vaccines [1,2]. While this suggests that coadministration causes an interaction resulting in a greater risk of adverse events following Immunization (AEFI) only the AEFI after the 4CMenB dose and not those occurring after routine vaccine immunizations were reported, underestimating the total risk associated with separate visits. For financial and practical reasons, coadministration of infant vaccines is preferred to separate visits. Separate visits may however be preferred if the sum of the AEFI risk at each visit is significantly smaller than the risk with coadministration and/or if the AEFI has a lesser severity.

For children who suffered an AEFI with a dose of 4CMenB, parents and providers are worried about the risk of recurrence and increased severity of the AEFI with administration of the next dose(s) of vaccine. This concern may lead to delay or cessation of immunization which can leave the child with suboptimal vaccine protection. While the 4CMenB clinical trials report the frequency of AEFI, they did not report their risk of recurrence and factors affecting this risk.

Given the high reactogenicity of Bexsero™ it is important to recalculate the risk of occurrence and severity of AEFI with the coadministration of Bexsero™ and routine vaccines compared to separate injections to assess the interaction occurring with the co-administration. We also need to estimate the risk of recurrence of AEFI at subsequent immunizations with the 4CMenB and assess if this risk varies with separate or coadministration with routine vaccines. This information will guide vaccine providers and public health authorities in both decisions regarding the regular vaccination program and for the management of safety concerns that will arise in patients presenting adverse events following 4CMenB immunization. To evaluate this, we propose to perform a secondary analysis of existing databases of three randomized trials (RCT)conducted in infants and toddlers by Novartis. The results of this study will be part of a PhD thesis in epidemiology and a manuscript will be submitted to a peer reviewed journal.

Study Data Provided

Study GSK-V72P12: A Phase 2b, Open Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules.
Study GSK-V72P13: A Phase 3, Partially Blinded, Randomized, Multi-Center, Controlled Study to Evaluate Immunogenicity, Safety and Lot to Lot Consistency of Novartis Meningococcal B Recombinant Vaccine When Administered With Routine Infant Vaccinations to Healthy Infants
Study GSK-V72P13E1: A Phase 3, Open Label, Multi-Center, Extension Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster at 12 Months of Age or as a Two-dose Catch-up to Healthy Toddlers Who Participated in Study V72P13

Statistical Analysis Plan

The statistical analysis plan will be added after the research is published.

Publication Citation

The publication citation will be added after the research is published.