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Investigating the Immune Response to 4CMenB in Infants

Primary Purpose

Meningitis

Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
4CMenB
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Meningitis

Eligibility Criteria

8 Weeks - 12 Weeks (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy infants of two Caucasian parents (self-defined by parent) born between 37 and 42 weeks of gestation aged 8-12 weeks at time of first visit
  • Parent or legal guardian willing and able to comply with the requirements of the protocol and have internet access for the duration of the study.
  • Parent/legal guardian who have given informed consent for their child's participation in the study

Exclusion Criteria:

  • Non-Caucasian infants
  • Children of parents who are on the delegation log for this study
  • Parent/ legal guardian under the age of 18
  • History of invasive meningococcal B disease
  • Previous vaccination with meningococcal serogroup B vaccine
  • History of being a household contact with a case of confirmed bacterial meningitis
  • Prior administration of any vaccine or planned administration of any vaccine not specified in the study protocol, with the exception of Hepatitis B vaccine and Influenza vaccines (which can be given 14 days before or after study vaccines), or BCG (which can be administered 28 days before or after study vaccines)
  • Prior or planned receipt of any other investigational vaccine or drug
  • Confirmed or suspected immunodeficiency
  • A family history of congenital or hereditary immunodeficiency, or maternal HIV
  • Receipt of more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid).
  • History of allergy to any component of the vaccine
  • Major congenital defects or serious chronic illness
  • History of any neurologic disorders or seizures
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period
  • Any other condition which, in the opinion of the investigator, may interfere with the ability to fulfil study requirements (this may include plans to move house and language comprehension).
  • No internet access for the duration of the study.

Sites / Locations

  • Oxford Vaccine Group, Centre for Clininal Vaccinology & Tropical Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

4CMenB - Test group

4CMenB - control group

Arm Description

Administered at 2, 4 and 12 months of age

Given at 5, 7 and 13 months of age

Outcomes

Primary Outcome Measures

Gene expression in whole blood at 4hr, 24hr, 3d and 7d time points following 4CMenB and routine infant vaccination given at 2, 4 and 12 months.
This is a descriptive study that aims to identify what genes are 'turned on' or 'turned off' following vaccination with 4CMenB and routine vaccines.

Secondary Outcome Measures

Full Information

First Posted
February 17, 2014
Last Updated
October 17, 2018
Sponsor
University of Oxford
Collaborators
Public Health England, Imperial College London, Novartis Vaccines, European Commission
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1. Study Identification

Unique Protocol Identification Number
NCT02080559
Brief Title
Investigating the Immune Response to 4CMenB in Infants
Official Title
A Randomised, Descriptive, Open Label, Study Exploring the Relationship Between Gene Expression Signatures With Reactogenicity and Immunogenicity Following Vaccination With Serogroup B Meningococcal Vaccine (4CMenB)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
July 21, 2014 (Actual)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
April 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Public Health England, Imperial College London, Novartis Vaccines, European Commission

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomised, open-label, single-centre, descriptive study aims to investigate gene expression (i.e what genes are 'switched on' and 'off') following vaccination with 4CMenB and to relate this to vaccine reactions and to immune response. 160 healthy Caucasian infants aged 8-12 weeks (at time of first visit) who have not yet received their routine infant immunisations will be recruited. Participation in the study will be limited to to Caucasian infants (defined as having two Caucasian parents). This is so that baseline variability in gene expression data which is to some degree affected by ethnicity is reduced. Participants will be randomised to either a 'test' group or 'control' group depending on what 4CMenB schedule they receive, with 80 infants in each. All participants will receive the usual paediatric immunisations according to the UK national immunisation schedule. In addition, participants in the test groups will receive 4CMenB at 2, 4 and at 12 months while those in the control groups will receive the same vaccine at 5, 7 and 13 months. Blood samples will be taken from each infant at specified time points before and after vaccination to address the objectives of the study. In addition, oro-pharyneal swabs will be obtained around different vaccination timepoints to investigate the effect of 4CMenB vaccination on the oro-pharyngeal Neisseria microbiome.
Detailed Description
The incidence of meningococcal disease is 0.2-14 per 100,000 in industrialized countries. In England and Wales, during the period 2005-2010, there were 900-1300 cases annually. Disease is commonest in infants, young children and adolescents and case fatality is high at 8-10%. Until recently there were no licensed vaccines against serogroup B meningococcal disease, although vaccines against epidemic strains of MenB have been used in several countries. Unfortunately, 4CMenB is associated with significant reactogenicity. This is presumably related to the presence of various bacterial surface components present in the outer membrane vessicles (OMVs), including lipopolysacchride (LPS), which are capable of activating the innate immune response. The host pathways responsible for reactogenicity to OMV vaccines, and indeed to other vaccines, are not yet established, and the relationship between reactogenicity and immunogenicity is not clear. This study will provide information about pathways and mechanisms of immunity and may identify gene expression signals which can be used in future vaccine design and evaluation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meningitis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
187 (Actual)

8. Arms, Groups, and Interventions

Arm Title
4CMenB - Test group
Arm Type
Experimental
Arm Description
Administered at 2, 4 and 12 months of age
Arm Title
4CMenB - control group
Arm Type
Active Comparator
Arm Description
Given at 5, 7 and 13 months of age
Intervention Type
Biological
Intervention Name(s)
4CMenB
Other Intervention Name(s)
Bexsero
Intervention Description
0.5ml IM
Primary Outcome Measure Information:
Title
Gene expression in whole blood at 4hr, 24hr, 3d and 7d time points following 4CMenB and routine infant vaccination given at 2, 4 and 12 months.
Description
This is a descriptive study that aims to identify what genes are 'turned on' or 'turned off' following vaccination with 4CMenB and routine vaccines.
Time Frame
13 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Weeks
Maximum Age & Unit of Time
12 Weeks
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy infants of two Caucasian parents (self-defined by parent) born between 37 and 42 weeks of gestation aged 8-12 weeks at time of first visit Parent or legal guardian willing and able to comply with the requirements of the protocol and have internet access for the duration of the study. Parent/legal guardian who have given informed consent for their child's participation in the study Exclusion Criteria: Non-Caucasian infants Children of parents who are on the delegation log for this study Parent/ legal guardian under the age of 18 History of invasive meningococcal B disease Previous vaccination with meningococcal serogroup B vaccine History of being a household contact with a case of confirmed bacterial meningitis Prior administration of any vaccine or planned administration of any vaccine not specified in the study protocol, with the exception of Hepatitis B vaccine and Influenza vaccines (which can be given 14 days before or after study vaccines), or BCG (which can be administered 28 days before or after study vaccines) Prior or planned receipt of any other investigational vaccine or drug Confirmed or suspected immunodeficiency A family history of congenital or hereditary immunodeficiency, or maternal HIV Receipt of more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid). History of allergy to any component of the vaccine Major congenital defects or serious chronic illness History of any neurologic disorders or seizures Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period Any other condition which, in the opinion of the investigator, may interfere with the ability to fulfil study requirements (this may include plans to move house and language comprehension). No internet access for the duration of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew J Pollard, PhD
Organizational Affiliation
Oxford Vaccine Group, University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oxford Vaccine Group, Centre for Clininal Vaccinology & Tropical Medicine
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33210468
Citation
O'Connor D, Pinto MV, Sheerin D, Tomic A, Drury RE, Channon-Wells S, Galal U, Dold C, Robinson H, Kerridge S, Plested E, Hughes H, Stockdale L, Sadarangani M, Snape MD, Rollier CS, Levin M, Pollard AJ. Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine. Mol Syst Biol. 2020 Nov;16(11):e9888. doi: 10.15252/msb.20209888.
Results Reference
derived

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Investigating the Immune Response to 4CMenB in Infants

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