MeningitisPhase 4NCT02080559
Investigating the Immune Response to 4CMenB in Infants
A Phase 4 study testing 4CMenB in people with Meningitis, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 12 weeksHealthy volunteers can take part
- Conditions the study is for
- Meningitis
- What is being tested?
- 4CMenB
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 187 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jul 2014to 27 Apr 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 12 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Oxford Vaccine Group, Centre for Clininal Vaccinology & Tropical Medicine
Oxford, OX3 7LE
About this study
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)
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.
Read more
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.
Read the 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.
- Conditions
- Meningitis
- Being tested
- 4CMenB
- Medical subject headings
- Meningitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4CMenBBiological
Also called Bexsero
0.5ml IM
| Study group | Role | What they receive |
|---|---|---|
| 4CMenB - Test group | Experimental | Administered at 2, 4 and 12 months of age Receives: Biological: 4CMenB |
| 4CMenB - control group | Active comparator | Given at 5, 7 and 13 months of age Receives: Biological: 4CMenB |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2014 (estimated)
- Study start21 Jul 2014
- Primary completionJun 2016
- Study completion27 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MeningitisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 187 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Public Health England, Imperial College London, Novartis Vaccines, European Commission
- Responsible party
- Sponsor
- Investigators
- Andrew J Pollard, PhD, Principal investigator, Oxford Vaccine Group, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02080559
- Sponsor's protocol ID
- OVG2012/05 EUCLIDS
- Status last verified
- Feb 2018
- First submitted
- 17 Feb 2014
- Last updated
- 19 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33210468
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02080559
- Acronym / sponsor ID
- OVG2012/05 EUCLIDS
- Conditions
- Meningitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 187 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Public Health England, Imperial College London, Novartis Vaccines, European Commission
- Study start
- 21 Jul 2014 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- 27 Apr 2018 (actual)
- First posted
- 6 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4CMenB - Test group | Experimental | Biological: 4CMenBAdministered at 2, 4 and 12 months of age |
| 4CMenB - control group | Active comparator | Biological: 4CMenBGiven at 5, 7 and 13 months of age |
Who may qualify
- Ages
- 8 to 12 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4CMenBAlso: Bexsero0.5ml IM | Biological | 4CMenB - Test group, 4CMenB - control group |
Primary outcome
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.
Time frame: 13 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
- Derived from this study: PubMed 33210468O'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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Pollard, PhD principal investigator
Oxford Vaccine Group, University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 4CMenB in people with Meningitis, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 13 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02080559, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2018.