Bexsero™and Routine Infant Vaccines: Effect of Coadministration on the Safety of Immunization

CHU de Quebec-Universite Laval4,535 enrolled

Overview

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 \[Priorix-Tetra™\]) \[1,2\].

Study Type

OBSERVATIONAL

Enrollment

4,535

Conditions

Meningococcal Infections

Eligibility

Sex: ALLMin age: 2 MonthsMax age: 14 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Fever

Temperature ≥ 38°C

Time frame: 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

Systemic reactions other than fever

systemic signs/symptoms (e.g. change in eating habits, sleepiness, unusual crying, vomiting, diarrhea, irritability…) without signs of localized infection (respiratory, urinary, etc...).

Time frame: 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

Fever or systemic reactions other than fever

all systemic signs/symptoms including fever (Temperature ≥ 38°C)

Injection site reactions

Time frame: AT RISK INTERVAL all injection site reactions regardless of their delay of onset. Baseline (CONTROL) risk null.