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

August 5, 2019 updated by: Gaston De Serres, CHU de Quebec-Universite Laval

Interaction Between Meningococcal Serogroup B Vaccine (Bexsero™) and Routine Infant Vaccines on the Risk of Occurrence and Recurrence of Adverse Events Following Immunization.

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4535

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 months to 1 year (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Coadministration B_RV246
Subjects in this group received 4CMenB vaccine at 2, 4, and 6 months of age, administered concomitantly with routine infant vaccinations (Infanrix Hexa+Prevenar).
Biological: 4CMenb
Other Names:
  • Bexsero
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar
Coadministration B_RV234
Subjects in this group received 4CMenB vaccine at 2, 3 and 4 months of age, administered concomitantly with routine infant vaccinations (Infanrix Hexa+Prevenar)..
Biological: 4CMenb
Other Names:
  • Bexsero
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar
Coadministration B_MMRV12
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.
Biological: MMRV
Other Names:
  • Priorix Tetra
Biological: 4CMenb
Other Names:
  • Bexsero
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar
Separate administration B246_RV357
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.
Biological: 4CMenb
Other Names:
  • Bexsero
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar
Separate administration B12_MMRV13
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.
Biological: MMRV
Other Names:
  • Priorix Tetra
Biological: 4CMenb
Other Names:
  • Bexsero
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar
Routine vaccines only at 2, 3 and 4 months of age (RV234)
Subjects in this group received routine infant vaccines (Infanrix Hexa+Prevenar) at 2, 3 and 4 months of age.
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar
Routine vaccines only at 2, 4 and 6 months of age.(RV246)
Subjects in this group received routine infant vaccines (Infanrix Hexa+Prevenar) at 2, 4 and 6 months of age.
Biological: diphtheria,tetanus,pertussis+polio+Hepatitis B+HiB
Other Names:
  • Infanrix Hexa
Biological: conjugated pneumococcal vaccine
Other Names:
  • Prevenar

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Fever
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
Temperature ≥ 38°C
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
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
systemic signs/symptoms (e.g. change in eating habits, sleepiness, unusual crying, vomiting, diarrhea, irritability…) without signs of localized infection (respiratory, urinary, etc...).
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
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
all systemic signs/symptoms including fever (Temperature ≥ 38°C)
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
Injection site reactions
Time Frame: AT RISK INTERVAL all injection site reactions regardless of their delay of onset. Baseline (CONTROL) risk null.
AT RISK INTERVAL all injection site reactions regardless of their delay of onset. Baseline (CONTROL) risk null.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CHU de Quebec-Universite Laval

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline
Canadian Immunization Research Network

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gaston De Serres, MD, PhD, CHU de Québec

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2008

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2010

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 14, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 7, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1224 (Lineberger Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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