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

Laval University

Status

Completed

Conditions

Meningococcal Infections

Treatments

Biological: MMRV

Biological: 4CMenb

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Biological: conjugated pneumococcal vaccine

Study type

Observational

Funder types

Other

NETWORK

Industry

Identifiers

NCT02712177

1224

Details and patient eligibility

About

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].

Enrollment

4,535 patients

Sex

All

Ages

2 to 14 months old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

4,535 participants in 7 patient groups

Coadministration B_RV246

Description:

Subjects in this group received 4CMenB vaccine at 2, 4, and 6 months of age, administered concomitantly with routine infant vaccinations (Infanrix Hexa+Prevenar).

Treatment:

Biological: conjugated pneumococcal vaccine

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Biological: 4CMenb

Coadministration B_RV234

Description:

Subjects in this group received 4CMenB vaccine at 2, 3 and 4 months of age, administered concomitantly with routine infant vaccinations (Infanrix Hexa+Prevenar)..

Treatment:

Biological: conjugated pneumococcal vaccine

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Biological: 4CMenb

Coadministration B_MMRV12

Description:

Subjects in this group previously received three doses of 4CMenB and routine vaccine at 2, 4 and 6 months of age,respectively. They also received a booster (fourth) dose at 12 months of age concomitantly with one dose of MMRV vaccine.

Treatment:

Biological: conjugated pneumococcal vaccine

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Biological: MMRV

Biological: 4CMenb

Separate administration B246_RV357

Description:

Subjects in this group received 4CMenB vaccine at 2, 4, and 6 months of age; routine infant vaccinations (Infanrix Hexa+Prevenar) were administered at 3, 5 and 7 months of age.

Treatment:

Biological: conjugated pneumococcal vaccine

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Biological: 4CMenb

Separate administration B12_MMRV13

Description:

Subjects in this group previously received three doses of 4CMenB and routine vaccines (Infanrix Hexa+Prevenar) at 2, 4 and 6 months of age. They also received a booster (fourth) dose of 4CMenB at 12 months of age and one dose of MMRV vaccine at 13 months of age.

Treatment:

Biological: conjugated pneumococcal vaccine

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Biological: MMRV

Biological: 4CMenb

Routine vaccines only at 2, 3 and 4 months of age (RV234)

Description:

Subjects in this group received routine infant vaccines (Infanrix Hexa+Prevenar) at 2, 3 and 4 months of age.

Treatment:

Biological: conjugated pneumococcal vaccine

Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB

Routine vaccines only at 2, 4 and 6 months of age.(RV246)