Clinical trial NCT02712177: Bexsero™and Routine Infant Vaccines: Effect of Coadministration on the Safety of Immunization
Official title: Interaction Between Meningococcal Serogroup B Vaccine (Bexsero™) and Routine Infant Vaccines on the Risk of Occurrence and Recurrence of Adverse Events Following Immunization.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Meningococcal Infections
Keywords: vaccine safety
interaction
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Canadian Immunization Research Network
First posted: 2016-03-18
Enrollment: 4535
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy children aged 2 to 14 months selected to participate in clinical trials assessing the safety and immunogenicity of 4 component meningococcal serogroup B vaccine (4CMenB) in Austria, Belgium, Czech Republic, Finland, Germany, Italy, Spain, United Kingdom.

Brief summary: Bexsero™ is a four component serogroup B meningococcal vaccine (4CMenB) licensed in Europe, Canada, and Australia in 2014. Prelicensure studies and post marketing surveillance data showed that 4CMenB has a high reactogenicity especially when coadministered with other infant 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 immunization at 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. The purpose of this study is 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 co-administration. Investigators will also 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. To achieve these purposes, investigators will perform a secondary analysis of the data of three randomized controlled trials (clinicaltrials.gov identifiers: NCT00657709, NCT00847145 and NCT00721396) that evaluated 5025 children aged 2 to 14 months of whom 4535 were randomized to receive 3 to 4 doses of 4CMenB concomitantly or alternatively with routine vaccinations (DTaP-Inactivated polio virus -HepatitisB/Haemophilus influenzae type b \[Infanrix Hexa™\], Pneumococcal conjugate vaccine, 7 valent \[Prevenar™\] or Measles-Mumps-Rubella-Varicella vaccine \[Priorix-Tetra™\]) \[1,2\].


Eligibility criteria: Inclusion Criteria:

* Healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age ≥ 37 weeks
* Parent/legal guardian has given written informed consent after the nature of the study has been explained.

Main exclusion Criteria :

* History of any meningococcal B or C vaccine administration; prior vaccination with routine infant vaccines (Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenzae type b (Hib), and Pneumococcal antigens);
* Previous ascertained or suspected disease caused by N. meningitidis; History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;
* Significant acute or chronic infection within the previous 7 days or axillary temperature major or equal to38 degrees within the previous day;
* Antibiotics within 6 days prior to enrollment;
* Any serious chronic or progressive disease;
* Known or suspected impairment or alteration of the immune system;
* Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation.

Primary outcomes:
measure: Fever
timeFrame: AT RISK INTERVAL 4CMenB and inactivated routine vaccines (InRV) : Onset 24 hours following immunization (post-Imm). MMRV: Onset day 5 to day 13 post-Imm.CONTROL INTERVAL 4CMenB and InRV : Onset day 4 to 7post-Imm . MMRV: Onset day 0 to 4 post-Imm
measure: Systemic reactions other than fever
timeFrame: AT RISK INTERVAL 4CMenB and InRV : Onset 24 hours post-Imm. MMRV: Onset day 5 to day 13 post-Imm.CONTROL INTERVAL 4CMenB and InRV : Onset day 4 to 7post-Imm . MMRV: Onset day 0 to 4 post-Imm
measure: Fever or systemic reactions other than fever
timeFrame: AT RISK INTERVAL 4CMenB and InRV : Onset 24 hours post-Imm. MMRV: Onset day 5 to day 13 post-Imm.CONTROL INTERVAL 4CMenB and InRV : Onset day 4 to 7post-Imm . MMRV: Onset day 0 to 4 post-Imm
measure: Injection site reactions
timeFrame: AT RISK INTERVAL all injection site reactions regardless of their delay of onset. Baseline (CONTROL) risk null.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: CHU de Quebec
name: Gaston De Serres, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gossger N, Snape MD, Yu LM, Finn A, Bona G, Esposito S, Principi N, Diez-Domingo J, Sokal E, Becker B, Kieninger D, Prymula R, Dull P, Ypma E, Toneatto D, Kimura A, Pollard AJ; European MenB Vaccine Study Group. Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial. JAMA. 2012 Feb 8;307(6):573-82. doi: 10.1001/jama.2012.85.
citation: Vesikari T, Esposito S, Prymula R, Ypma E, Kohl I, Toneatto D, Dull P, Kimura A; EU Meningococcal B Infant Vaccine Study group. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet. 2013 Mar 9;381(9869):825-35. doi: 10.1016/S0140-6736(12)61961-8.
citation: Baker MA, Lieu TA, Li L, Hua W, Qiang Y, Kawai AT, Fireman BH, Martin DB, Nguyen MD. A vaccine study design selection framework for the postlicensure rapid immunization safety monitoring program. Am J Epidemiol. 2015 Apr 15;181(8):608-18. doi: 10.1093/aje/kwu322. Epub 2015 Mar 13.
citation: Zafack JG, Bureau A, Skowronski DM, De Serres G. Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials. BMJ Open. 2019 May 19;9(5):e026953. doi: 10.1136/bmjopen-2018-026953.