MeningitisPhase 3NCT00901940
Understanding the Immune Response to Meningitis Vaccines
A Phase 3 study testing Meningococcal (Groups A, C, Y and W-135) Conjugate and Meningococcal polysaccharide A, C, Y and W135 and Menveo in people with Meningitis and Septicemia, run by University of Oxford at 1 site in United Kingdom.
Trial summary
The purpose of the study is to evaluate and compare the immune response to two vaccines against 4 related bacteria: meningococcal serogroups A, C, W-135 and Y. These bacteria can cause meningitis and /or septicaemia (blood poisoning). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Meningitis, Septicemia
- What is being tested?
- Meningococcal (Groups A, C, Y and W-135) Conjugate and Meningococcal polysaccharide A, C, Y and W135 and Menveo
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2009to Oct 2010
- Phase
- Phase 3
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent for participation after the nature of the study has been explained
- Male or Female, aged 18- 70 years inclusive
- In good health as determined by:
- Medical history
- History-directed physical examination
- Clinical judgment of the investigator
Show all 9Show fewer
- Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
- Able (in the Investigator's opinion) and willing to comply with all study requirements
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study
Who cannot join
- Are unwilling or unable to give written informed consent to participate in the study
- Have previously received any meningococcal vaccine (this will be confirmed with the participant's general practitioner after enrolment)
- Have previously been diagnosed with laboratory confirmed meningococcal disease
- Have a history of any anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component
- Have a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):
- Receipt of any immunosuppressive therapy
Show all 14Show fewer
- Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroid therapy* (*prednisolone or equivalent for more than two consecutive weeks within the past 3 months).
- Have a suspected or known HIV infection or HIV related disease
- Have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months
- Have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time
- Have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
- Participation in another clinical trial investigating a vaccine, a drug, a medical device, or a medical procedure
- Pregnancy as confirmed by a positive pregnancy test
- Currently breast-feeding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine
Oxford, OX3 7LJ
About this study
Official title: Single Centre Open-Label Randomised Trial of Meningococcal Serogroup ACYW-135 B Cell Response to Primary & Booster Doses of ACWY Conjugate Vaccine & Primary Dose of ACWY Polysaccharide With Booster Dose of ACWY Conjugate in Adults
The purpose of the study is to evaluate and compare the immune response to two vaccines against 4 related bacteria: meningococcal serogroups A, C, W-135 and Y. These bacteria can cause meningitis and /or septicaemia (blood poisoning). The two vaccines are a protein-polysaccharide conjugate vaccine (MenACWY)and a meningococcal plain polysaccharide vaccine(MenACWY PS). Both vaccines are licensed and are currently used for travellers to areas with a high incidence of invasive meningococcal disease. However, plain polysaccharide vaccines are known to be poorly immunogenic in children and they do not stimulate immunological memory, apart from the serogroup A component. In contrast, a protein-polysaccharide conjugate vaccine against meningococcal serogroups A, C, W-135 and Y has been found to be immunogenic in infants and to be able to induce immunological memory.
The proposed study is a single centre, open-label, randomised, controlled study in 150 healthy adults aged 18-70 years. The participants will be given either 2 injections of the meningococcal protein-polysaccharide conjugate vaccine one month apart, or one injection of the meningococcal plain polysaccharide vaccine followed one month later with an injection of the meningococcal conjugate vaccine. Blood samples will be collected before immunisation and at several time points following immunisations to evaluate the level of meningococcal specific antibody induced by two different vaccination regimes. The data derived from the study will be relevant in determining which of these vaccines should be used in preference in travellers who are receiving immunisation against meningococcal disease before travelling to high risk areas. Additionally, a number of scientific questions regarding the nature of the immune response to the two vaccines (specifically looking at the white blood cells responsible for producing antibodies, known as B cells) and the role of genetic variations in influencing the vaccine recipient's immune response will be addressed in the study.
Read the detailed description
In this single centre, open-label, randomised, controlled study of 150 healthy adults aged 18-70 years we will be evaluating the immune response to immunisation with 2 different vaccines against 4 related bacteria known as Neisseria meningitidis serogroups A, C, W-135 and Y. These bacteria (also known as meningococci) can produce meningitis and septicaemia (blood poisoning). The first vaccine, which has been used as a travel vaccine in the UK for several years, is known as the MenACWY plain polysaccharide (MenACWY PS). The other vaccine, known as the MenACWY conjugate vaccine (MenACWY) was licensed in the UK in March 2010 and is now recommended as a travel vaccine by the Department of Health.
In order to evaluate the immune response to these vaccines we will be measuring not only the blood levels of antibodies specific to serogroup A, C, W-135 and Y meningococci, but also the population of white blood cells known as B cells which produce these antibodies. Two forms of these B cells will be measured, the plasma cells (which actively produce antibodies) and memory B cells (which do not produce antibodies but persist in the body and can be stimulated to turn into plasma cells when required).
Participants will be randomised into group I or group II on a 1:1 basis to receive either MenACWY or MenACWY PS. One month later, all participants will receive a booster dose of the MenACWY conjugate vaccine. The ACWY polysaccharide vaccine will be administered subcutaneously, and the MenACWY conjugate vaccine will be given intramuscularly. Each participant will be observed for at least 15 minutes after vaccination for any immediate reactions.
Blood samples will be collected from each participant for analysis prior to each immunisation, 7 days following the first immunisation and 7 and 28 days following the second immunisation. The volume of blood samples obtained at each timepoint will be 20 mLs. Blood will be used for antibody analysis (by ELISA), B cell analysis (by ELISpot)and DNA extraction for genetic analysis.
In summary, participants enrolled in this study will have a total of 5 visits in a period of 2 months. They will receive two doses of the MenACWY conjugate vaccine or one dose of the ACWY polysaccharide vaccine followed by one dose of the MenACWY conjugate vaccine. During this period they will have a total of 5 blood samples taken (5x20mL= 100 mL of blood taken in a 2 month period).
- Conditions
- Meningitis, Septicemia
- Being tested
- Meningococcal (Groups A, C, Y and W-135) Conjugate, Meningococcal polysaccharide A, C, Y and W135 and Menveo
- Medical subject headings
- Meningitis, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meningococcal (Groups A, C, Y and W-135) ConjugateBiological
Also called MenACWY, Menveo
2 x 0.5 mL dose
Meningococcal polysaccharide A, C, Y and W135 and MenveoBiological
Also called ACWY Vax, Menveo
1 x 0.5 mL dose of ACWY Vax, 1 x 0.5 mL dose of Menveo
| Study group | Role | What they receive |
|---|---|---|
| MenACWY Plain Polysaccharide (ACWY Vax) | Active comparator | The MenACWY Plain Polysaccharide Vaccine, which is already licensed and is used as a travel vaccine, is known as the MenACWY plain polysaccharide (ACWY Vax). Participants in this arm will receive 1 dose of the MenACWY plain polysaccharide (ACWY Vax) and 1 dose of the MenACWY conjugate (MenACWY). Receives: Biological: Meningococcal polysaccharide A, C, Y and W135 and Menveo |
| MenACWY conjugate | Active comparator | The MenACWY conjugate vaccine was licensed in the UK in March 2010, and is known as the MenACWY conjugate vaccine (Menveo). Participants in this arm will receive 2 doses of the MenACWY conjugate vaccine. Receives: Biological: Meningococcal (Groups A, C, Y and W-135) Conjugate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be whether the SBA GMT at day 7 following MenACWY is ≥ 30% greater than that observed at day 7 following MenACWY PS.
Measured: Day 7
Secondary outcomes (5)
The measurement of meningococcal serogroup C SBAs (using human complement) at day 7 following the initial immunisation with MenACWY and MenACWY PS.
Measured: Day 7
The measurement of meningococcal serogroup A and C specific SBAs (using human complement) at day 28 following the initial immunisation with MenACWY and MenACWY PS, and at day 7 and day 28 following the 'follow up' immunisation with MenACWY.
Measured: Day 7-28
Meningococcal serogroup W-135 and Y SBAs will also be performed on a subset of samples obtained at the above timepoints.
Measured: Day 7-28
The measurement of meningococcal serogroup A, C, W-135 and Y specific memory B cells and plasma B cells at day 7, and memory B cells at day 28 after first immunisation with MenACWY and MenACWY PS, and after the 'follow up' immunisation with MenACWY.
Measured: Day 7-56
Other assessments of the immune response to MenACWY and MenACWY PS (e.g. measurement of meningococcal serogroup A, C, W-135 and Y specific IgG by ELISA) may also be performed.
Measured: Day 7-56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2009 (estimated)
- Study startJun 2009
- Primary completionOct 2010
- Study completionOct 2010
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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Vaccines
- Investigators
- Andrew Pollard, FRCPCH, PhD, Principal investigator, University of Oxford, Department of Paediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00901940
- Sponsor's protocol ID
- 2007/04
- Status last verified
- Jun 2014
- First submitted
- 13 May 2009
- Last updated
- 5 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Ramasamy MN, Clutterbuck EA, Haworth K, Bowman J, Omar O, Thompson AJ, Blanchard-Rohner G, Yu LM, Snape MD, Pollard AJ. Randomized clinical trial to evaluate the immunogenicity of quadrivalent meningococcal conjugate and polysaccharide vaccines in adults in the United kingdom. Clin Vaccine Immunol. 2014 Aug;21(8):1164-8. doi: 10.1128/CVI.00099-14. Epub 2014 Jun 25.
PubMed 24964805
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Centre Open-Label Randomised Trial of Meningococcal Serogroup ACYW-135 B Cell Response to Primary & Booster Doses of ACWY Conjugate Vaccine & Primary Dose of ACWY Polysaccharide With Booster Dose of ACWY Conjugate in Adults
- ClinicalTrials.gov ID
- NCT00901940
- Acronym / sponsor ID
- 2007/04
- Conditions
- Meningitis, Septicemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Novartis Vaccines
- Study start
- Jun 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 14 May 2009 (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.
The purpose of the study is to evaluate and compare the immune response to two vaccines against 4 related bacteria: meningococcal serogroups A, C, W-135 and Y. These bacteria can cause meningitis and /or septicaemia (blood poisoning). The two vaccines are a protein-polysaccharide conjugate vaccine (MenACWY)and a meningococcal plain polysaccharide vaccine(MenACWY PS). Both vaccines are licensed and are currently used for travellers to areas with a high incidence of invasive meningococcal disease. However, plain polysaccharide vaccines are known to be poorly immunogenic in children and they do not stimulate immunological memory, apart from the serogroup A component. In contrast, a protein-polysaccharide conjugate vaccine against meningococcal serogroups A, C, W-135 and Y has been found to be immunogenic in infants and to be able to induce immunological memory.
The proposed study is a single centre, open-label, randomised, controlled study in 150 healthy adults aged 18-70 years. The participants will be given either 2 injections of the meningococcal protein-polysaccharide conjugate vaccine one month apart, or one injection of the meningococcal plain polysaccharide vaccine followed one month later with an injection of the meningococcal conjugate vaccine. Blood samples will be collected before immunisation and at several time points following immunisations to evaluate the level of meningococcal specific antibody induced by two different vaccination regimes. The data derived from the study will be relevant in determining which of these vaccines should be used in preference in travellers who are receiving immunisation against meningococcal disease before travelling to high risk areas. Additionally, a number of scientific questions regarding the nature of the immune response to the two vaccines (specifically looking at the white blood cells responsible for producing antibodies, known as B cells) and the role of genetic variations in influencing the vaccine recipient's immune response will be addressed in the study.
Detailed description
In this single centre, open-label, randomised, controlled study of 150 healthy adults aged 18-70 years we will be evaluating the immune response to immunisation with 2 different vaccines against 4 related bacteria known as Neisseria meningitidis serogroups A, C, W-135 and Y. These bacteria (also known as meningococci) can produce meningitis and septicaemia (blood poisoning). The first vaccine, which has been used as a travel vaccine in the UK for several years, is known as the MenACWY plain polysaccharide (MenACWY PS). The other vaccine, known as the MenACWY conjugate vaccine (MenACWY) was licensed in the UK in March 2010 and is now recommended as a travel vaccine by the Department of Health.
In order to evaluate the immune response to these vaccines we will be measuring not only the blood levels of antibodies specific to serogroup A, C, W-135 and Y meningococci, but also the population of white blood cells known as B cells which produce these antibodies. Two forms of these B cells will be measured, the plasma cells (which actively produce antibodies) and memory B cells (which do not produce antibodies but persist in the body and can be stimulated to turn into plasma cells when required).
Participants will be randomised into group I or group II on a 1:1 basis to receive either MenACWY or MenACWY PS. One month later, all participants will receive a booster dose of the MenACWY conjugate vaccine. The ACWY polysaccharide vaccine will be administered subcutaneously, and the MenACWY conjugate vaccine will be given intramuscularly. Each participant will be observed for at least 15 minutes after vaccination for any immediate reactions.
Blood samples will be collected from each participant for analysis prior to each immunisation, 7 days following the first immunisation and 7 and 28 days following the second immunisation. The volume of blood samples obtained at each timepoint will be 20 mLs. Blood will be used for antibody analysis (by ELISA), B cell analysis (by ELISpot)and DNA extraction for genetic analysis.
In summary, participants enrolled in this study will have a total of 5 visits in a period of 2 months. They will receive two doses of the MenACWY conjugate vaccine or one dose of the ACWY polysaccharide vaccine followed by one dose of the MenACWY conjugate vaccine. During this period they will have a total of 5 blood samples taken (5x20mL= 100 mL of blood taken in a 2 month period).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MenACWY Plain Polysaccharide (ACWY Vax) | Active comparator | Biological: Meningococcal polysaccharide A, C, Y and W135 and MenveoThe MenACWY Plain Polysaccharide Vaccine, which is already licensed and is used as a travel vaccine, is known as the MenACWY plain polysaccharide (ACWY Vax). Participants in this arm will receive 1 dose of the MenACWY plain polysaccharide (ACWY Vax) and 1 dose of the MenACWY conjugate (MenACWY). |
| MenACWY conjugate | Active comparator | Biological: Meningococcal (Groups A, C, Y and W-135) ConjugateThe MenACWY conjugate vaccine was licensed in the UK in March 2010, and is known as the MenACWY conjugate vaccine (Menveo). Participants in this arm will receive 2 doses of the MenACWY conjugate vaccine. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Participant is willing and able to give informed consent for participation after the nature of the study has been explained
- Male or Female, aged 18- 70 years inclusive
- In good health as determined by:
- Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
- Able (in the Investigator's opinion) and willing to comply with all study requirements
Key exclusion criteria (14 listed)
- Are unwilling or unable to give written informed consent to participate in the study
- Have previously received any meningococcal vaccine (this will be confirmed with the participant's general practitioner after enrolment)
- Have previously been diagnosed with laboratory confirmed meningococcal disease
- Have a history of any anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component
- Have a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):
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 |
|---|---|---|
| Meningococcal (Groups A, C, Y and W-135) ConjugateAlso: MenACWY, Menveo2 x 0.5 mL dose | Biological | MenACWY conjugate |
| Meningococcal polysaccharide A, C, Y and W135 and MenveoAlso: ACWY Vax, Menveo1 x 0.5 mL dose of ACWY Vax, 1 x 0.5 mL dose of Menveo | Biological | MenACWY Plain Polysaccharide (ACWY Vax) |
Primary outcome
The primary endpoint will be whether the SBA GMT at day 7 following MenACWY is ≥ 30% greater than that observed at day 7 following MenACWY PS.
Time frame: Day 7
5 secondary outcomes
The measurement of meningococcal serogroup C SBAs (using human complement) at day 7 following the initial immunisation with MenACWY and MenACWY PS.
Time frame: Day 7
The measurement of meningococcal serogroup A and C specific SBAs (using human complement) at day 28 following the initial immunisation with MenACWY and MenACWY PS, and at day 7 and day 28 following the 'follow up' immunisation with MenACWY.
Time frame: Day 7-28
Meningococcal serogroup W-135 and Y SBAs will also be performed on a subset of samples obtained at the above timepoints.
Time frame: Day 7-28
The measurement of meningococcal serogroup A, C, W-135 and Y specific memory B cells and plasma B cells at day 7, and memory B cells at day 28 after first immunisation with MenACWY and MenACWY PS, and after the 'follow up' immunisation with MenACWY.
Time frame: Day 7-56
Other assessments of the immune response to MenACWY and MenACWY PS (e.g. measurement of meningococcal serogroup A, C, W-135 and Y specific IgG by ELISA) may also be performed.
Time frame: Day 7-56
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 5 Dec 2014.
- Background: PubMed 24964805Ramasamy MN, Clutterbuck EA, Haworth K, Bowman J, Omar O, Thompson AJ, Blanchard-Rohner G, Yu LM, Snape MD, Pollard AJ. Randomized clinical trial to evaluate the immunogenicity of quadrivalent meningococcal conjugate and polysaccharide vaccines in adults in the United kingdom. Clin Vaccine Immunol. 2014 Aug;21(8):1164-8. doi: 10.1128/CVI.00099-14. Epub 2014 Jun 25.
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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 Pollard, FRCPCH, PhD principal investigator
University of Oxford, Department of Paediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Meningococcal (Groups A, C, Y and W-135) Conjugate and Meningococcal polysaccharide A, C, Y and W135 and Menveo in people with Meningitis and Septicemia, 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 9 inclusion and 14 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 5 Dec 2014. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
The primary endpoint will be whether the SBA GMT at day 7 following MenACWY is ≥ 30% greater than that observed at day 7 following MenACWY PS. (time frame: Day 7). 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 NCT00901940, 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 5 Dec 2014.