Infections, MeningococcalPhase 4NCT00271479
Fractional Dose Tetravalent A, C, Y, W135 Meningococcal Polysaccharide Vaccine
A Phase 4 study testing A, C, Y, W135 meningococcal polysaccharide vaccine in people with Infections, Meningococcal and Meningitis, Meningococcic, run by Epicentre at 2 sites in 2 countries.
Trial summary
Hypothesis: Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could confer a similar functional immunogenic response as the dose of 50 μg currently being used, and subsequently be equally protective. Read more about this study
- Who is it for?
- Ages 2 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Infections, Meningococcal, Meningitis, Meningococcic
- What is being tested?
- A, C, Y, W135 meningococcal polysaccharide vaccine
- Type of treatment
- Vaccines
- How many people
- 720 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2004to Nov 2006
- 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 2 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Volunteers should not be suffering of severe chronic disease or a known congenital or acquired immunodeficiency. A medical exam will be performed by a medical doctor before inclusion.
- Volunteers must be living in the Mbarara district and within 15 km from the site of immunization. Volunteers should be residents of the chosen site and should express no plan of moving from this area during the study period.
- Volunteers must be available for follow-up for the duration of the study (minimum of 24 months).
Who cannot join
- Volunteers with severe chronic disease or with a general condition requiring hospital admission.
- Volunteers with a known congenital or acquired immunodeficiency (e.g. HIV). Diagnosis will be presumptive based on the medical background and the clinical examination. No serological HIV testing will be performed.
- Evidence of any concomitant infection at the time of presentation (including rashes other than scabies; ear, nose or throat infections; and abnormal respiratory system examination).
- The patient has any other underlying diseases that compromise the diagnosis and the evaluation of the response to the study medication.
- History of serious adverse reactions to vaccines such as anaphylaxis or related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain.
- Malnutrition: The nutritional assessment of children aged 24-59 months, a weight-for-height (W/H) index, will be calculated. This index is expressed in standard deviations of a normalised distribution of a reference population 38 (National Centre for Health Statistics, USA). Children under 5 years old with a Z-score inferior to -2 will be excluded. For children over 5 or adults, the clinical examination will be considered.
- Pregnant women and lactating women are not eligible for this trial. All women of child-bearing age must provide a urine sample for pregnancy testing before inclusion and, for sub-group "b", before the second vaccine injection.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Assay of the Immunogenicity of Fractional Dose Tetravalent A, C, Y, W135 Meningococcal Polysaccharide Vaccine in Africa
Hypothesis:
Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could confer a similar functional immunogenic response as the dose of 50 μg currently being used, and subsequently be equally protective.
Read more
The purpose of this study is to evaluate the use of fractional dose tetravalent meningococcal polysaccharide vaccine to control outbreak especially caused by N. meningitidis serogroup W135
Primary Objectives:
- To measure the immunogenicity of a dose corresponding to one fifth of the amount of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 10 μg for each component; and
- To measure the immunogenicity of a dose corresponding to one tenth of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 5 μg for each component.
Read the detailed description
In 2002, an epidemic of meningococcal disease started in Burkina Faso and Neisseria meningitidis serogroup W135 was identified as the causative organism. This event followed the outbreaks of 2000 and 2001 in Mecca, Saudi Arabia, and was the first large epidemic caused by serogroup W135. Mass vaccination of the population with the only vaccine protecting against W135, i.e. the tetravalent A/C/Y/W135 polysaccharide vaccine (TPSV), was not possible because of the global shortage in supply, in addition to its cost. In 2003, GlaxoSmithKline (GSK) produced a trivalent polysaccharide vaccine A/C/W135 for US$ 1.5. This vaccine was used in Burkina Faso in the new epidemic faced by this country in 2003. However, availability and affordability of the tetravalent A/C/Y/W135 polysaccharide vaccine and of the trivalent A/C/W135 polysaccharide vaccine are still under discussion between the WHO and the producers. The risk of further epidemics due to the W135 strain in other African countries is of high concern for the scientific community.
The current dose of the licensed tetravalent A/C/Y/W135 polysaccharide vaccine contains 50 μg of each polysaccharide component. During the 1980's, researchers from the Walter Reed Army Institute of Research (WRAIR) did extensive works on the immunogenicity of meningococcal polysaccharide vaccines in adults. A first study performed by Griffiss et al. demonstrated that doses of 5 μg of group Y and group W135 polysaccharides were as effective as doses of 50 μg in inducing production of bactericidal antibody amounts correlating with functional immunity (Griffiss et al. Mil Med 1985; 150: 529-33). A second study concluded that doses of 7.5 μg (Y and W) and 15 μg (A and C) were sufficient to induce equivalent binding and bactericidal antibody responses as 50 μg (Griffiss et al. Infect Immun 1982; 37: 205-8). In a more recent study from Granoff et al., 1/50 (1 mcg) of the ordinary dose of tetravalent A/C/Y/W135 vaccine was given (Granoff et al. J Infect Dis 1998; 178: 870-4). The antibody responses to A and C have been measured, and this low dose was sufficient to mount a C response in most of the subjects, but the dose was less effective in eliciting a response to A. The antibody responses to W135 and Y were not reported.
Hypothesis:
Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could confer a similar functional immunogenic response as the dose of 50 μg currently being used, and subsequently be equally protective.
It would potentially bring two major benefits. Firstly, it would increase the number of tetravalent vaccine doses available on the market. Secondly, it would decrease the cost of the individual vaccine dose. As a result, more people could be vaccinated, and thereby protected against the disease, and to a lower price.
Results obtained with the study on the tetravalent A/C/Y/W135 polysaccharide vaccine would be valid for the trivalent A/C/W135 polysaccharide vaccine.
- Being tested
- A, C, Y, W135 meningococcal polysaccharide vaccine
- Keywords
- Meningitis, Dose-Response Relationship, Immunologic, Neisseria meningitidis, Outbreaks, Vaccine, Africa, Uganda, Prevention of Neisseria meningitidis infections, In outbreak contexts in developing countries
- Medical subject headings
- Meningococcal Infections, Meningitis, Meningococcal, Meningitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A, C, Y, W135 meningococcal polysaccharide vaccineBiological
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure the immunogenicity of a dose corresponding to one fifth of the amount of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 10µg for each component
To measure the immunogenicity of a dose corresponding to one tenth of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 5µg for each component
Secondary outcomes (4)
To determine the pharyngeal carriage of N. meningitidis and in particular W135 strains in the study population
To determine the natural immunity towards N. meningitidis serogroup A, C, Y and W135 before immunisation in the study population
To measure a possible waning of immunity at one year and at two years after immunisation
To measure the immune response after challenging with a second dose of the commercialised meningococcal A/C/Y/W135 polysaccharide vaccine after one year, in a group of volunteers who have received a reduced dose on day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2006 (estimated)
- Study startJun 2004
- Study completionNov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Infections, MeningococcalStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Enrolment
- 720 participants
Sponsor and investigators
- Lead sponsor
- Epicentre
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian Institute of Public Health, University of Oslo, Medecins Sans Frontieres, Netherlands
- Investigators
- Philippe J Guerin, MD, MPH, PhD, Principal investigator, EpicentreDominique A Caugant, PhD, Principal investigator, Norwegian Institute of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00271479
- Sponsor's protocol ID
- MB-04-MEN-04
- Status last verified
- Dec 2006
- First submitted
- 29 Dec 2005
- Last updated
- 22 Dec 2006
- Results posted
- No
Publications
Griffiss JM, Brandt BL, Broud DD. Human immune response to various doses of group Y and W135 meningococcal polysaccharide vaccines. Infect Immun. 1982 Jul;37(1):205-8. doi: 10.1128/iai.37.1.205-208.1982.
PubMed 6809627Griffiss JM, Brandt BL, Broud DD, Altieri PL, Berman SL. Relationship of dose to the reactogenicity and immunogenicity of meningococcal polysaccharide vaccines in adults. Mil Med. 1985 Oct;150(10):529-33. No abstract available.
PubMed 3934585Granoff DM, Gupta RK, Belshe RB, Anderson EL. Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination. J Infect Dis. 1998 Sep;178(3):870-4. doi: 10.1086/515346.
PubMed 9728562Guerin PJ, Naess LM, Fogg C, Rosenqvist E, Pinoges L, Bajunirwe F, Nabasumba C, Borrow R, Froholm LO, Ghabri S, Batwala V, Twesigye R, Aaberge IS, Rottingen JA, Piola P, Caugant DA. Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda. PLoS Negl Trop Dis. 2008;2(12):e342. doi: 10.1371/journal.pntd.0000342. Epub 2008 Dec 2.
PubMed 19048025
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assay of the Immunogenicity of Fractional Dose Tetravalent A, C, Y, W135 Meningococcal Polysaccharide Vaccine in Africa
- ClinicalTrials.gov ID
- NCT00271479
- Acronym / sponsor ID
- MB-04-MEN-04
- Keywords
- Meningitis, Dose-Response Relationship, Immunologic, Neisseria meningitidis, Outbreaks, Vaccine, Africa, Uganda, Prevention of Neisseria meningitidis infections
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 720 participants
- Lead sponsor
- EpicentreUniversity, hospital or other
- Collaborators
- Norwegian Institute of Public Health, University of Oslo, Medecins Sans Frontieres, Netherlands
- Study start
- Jun 2004
- Study completion
- Nov 2006
- First posted
- 2 Jan 2006 (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.
Hypothesis:
Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could confer a similar functional immunogenic response as the dose of 50 μg currently being used, and subsequently be equally protective.
The purpose of this study is to evaluate the use of fractional dose tetravalent meningococcal polysaccharide vaccine to control outbreak especially caused by N. meningitidis serogroup W135
Primary Objectives:
- To measure the immunogenicity of a dose corresponding to one fifth of the amount of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 10 μg for each component; and
- To measure the immunogenicity of a dose corresponding to one tenth of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 5 μg for each component.
Detailed description
In 2002, an epidemic of meningococcal disease started in Burkina Faso and Neisseria meningitidis serogroup W135 was identified as the causative organism. This event followed the outbreaks of 2000 and 2001 in Mecca, Saudi Arabia, and was the first large epidemic caused by serogroup W135. Mass vaccination of the population with the only vaccine protecting against W135, i.e. the tetravalent A/C/Y/W135 polysaccharide vaccine (TPSV), was not possible because of the global shortage in supply, in addition to its cost. In 2003, GlaxoSmithKline (GSK) produced a trivalent polysaccharide vaccine A/C/W135 for US$ 1.5. This vaccine was used in Burkina Faso in the new epidemic faced by this country in 2003. However, availability and affordability of the tetravalent A/C/Y/W135 polysaccharide vaccine and of the trivalent A/C/W135 polysaccharide vaccine are still under discussion between the WHO and the producers. The risk of further epidemics due to the W135 strain in other African countries is of high concern for the scientific community.
The current dose of the licensed tetravalent A/C/Y/W135 polysaccharide vaccine contains 50 μg of each polysaccharide component. During the 1980's, researchers from the Walter Reed Army Institute of Research (WRAIR) did extensive works on the immunogenicity of meningococcal polysaccharide vaccines in adults. A first study performed by Griffiss et al. demonstrated that doses of 5 μg of group Y and group W135 polysaccharides were as effective as doses of 50 μg in inducing production of bactericidal antibody amounts correlating with functional immunity (Griffiss et al. Mil Med 1985; 150: 529-33). A second study concluded that doses of 7.5 μg (Y and W) and 15 μg (A and C) were sufficient to induce equivalent binding and bactericidal antibody responses as 50 μg (Griffiss et al. Infect Immun 1982; 37: 205-8). In a more recent study from Granoff et al., 1/50 (1 mcg) of the ordinary dose of tetravalent A/C/Y/W135 vaccine was given (Granoff et al. J Infect Dis 1998; 178: 870-4). The antibody responses to A and C have been measured, and this low dose was sufficient to mount a C response in most of the subjects, but the dose was less effective in eliciting a response to A. The antibody responses to W135 and Y were not reported.
Hypothesis:
Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could confer a similar functional immunogenic response as the dose of 50 μg currently being used, and subsequently be equally protective.
It would potentially bring two major benefits. Firstly, it would increase the number of tetravalent vaccine doses available on the market. Secondly, it would decrease the cost of the individual vaccine dose. As a result, more people could be vaccinated, and thereby protected against the disease, and to a lower price.
Results obtained with the study on the tetravalent A/C/Y/W135 polysaccharide vaccine would be valid for the trivalent A/C/W135 polysaccharide vaccine.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
Who may qualify
- Ages
- 2 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Volunteers should not be suffering of severe chronic disease or a known congenital or acquired immunodeficiency. A medical exam will be performed by a medical doctor before inclusion.
- Volunteers must be living in the Mbarara district and within 15 km from the site of immunization. Volunteers should be residents of the chosen site and should express no plan of moving from this area during the study period.
- Volunteers must be available for follow-up for the duration of the study (minimum of 24 months).
Key exclusion criteria (7 listed)
- Volunteers with severe chronic disease or with a general condition requiring hospital admission.
- Volunteers with a known congenital or acquired immunodeficiency (e.g. HIV). Diagnosis will be presumptive based on the medical background and the clinical examination. No serological HIV testing will be performed.
- Evidence of any concomitant infection at the time of presentation (including rashes other than scabies; ear, nose or throat infections; and abnormal respiratory system examination).
- The patient has any other underlying diseases that compromise the diagnosis and the evaluation of the response to the study medication.
- History of serious adverse reactions to vaccines such as anaphylaxis or related symptoms such as hives, respiratory difficulty, angioedema and abdominal pain.
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 |
|---|---|---|
| A, C, Y, W135 meningococcal polysaccharide vaccine | Biological | – |
Primary outcome
To measure the immunogenicity of a dose corresponding to one fifth of the amount of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 10µg for each component
To measure the immunogenicity of a dose corresponding to one tenth of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 5µg for each component
4 secondary outcomes
To determine the pharyngeal carriage of N. meningitidis and in particular W135 strains in the study population
To determine the natural immunity towards N. meningitidis serogroup A, C, Y and W135 before immunisation in the study population
To measure a possible waning of immunity at one year and at two years after immunisation
To measure the immune response after challenging with a second dose of the commercialised meningococcal A/C/Y/W135 polysaccharide vaccine after one year, in a group of volunteers who have received a reduced dose on day 0
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 22 Dec 2006.
- Background: PubMed 6809627Griffiss JM, Brandt BL, Broud DD. Human immune response to various doses of group Y and W135 meningococcal polysaccharide vaccines. Infect Immun. 1982 Jul;37(1):205-8. doi: 10.1128/iai.37.1.205-208.1982.
- Background: PubMed 3934585Griffiss JM, Brandt BL, Broud DD, Altieri PL, Berman SL. Relationship of dose to the reactogenicity and immunogenicity of meningococcal polysaccharide vaccines in adults. Mil Med. 1985 Oct;150(10):529-33. No abstract available.
- Background: PubMed 9728562Granoff DM, Gupta RK, Belshe RB, Anderson EL. Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination. J Infect Dis. 1998 Sep;178(3):870-4. doi: 10.1086/515346.
- Derived from this study: PubMed 19048025Guerin PJ, Naess LM, Fogg C, Rosenqvist E, Pinoges L, Bajunirwe F, Nabasumba C, Borrow R, Froholm LO, Ghabri S, Batwala V, Twesigye R, Aaberge IS, Rottingen JA, Piola P, Caugant DA. Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda. PLoS Negl Trop Dis. 2008;2(12):e342. doi: 10.1371/journal.pntd.0000342. Epub 2008 Dec 2.
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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.
Philippe J Guerin, MD, MPH, PhD principal investigator
Epicentre
Dominique A Caugant, PhD principal investigator
Norwegian Institute of Public Health
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing A, C, Y, W135 meningococcal polysaccharide vaccine in people with Infections, Meningococcal and Meningitis, Meningococcic, run by Epicentre at 2 sites in 2 countries.
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 7 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 22 Dec 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway, Uganda. 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?
To measure the immunogenicity of a dose corresponding to one fifth of the amount of the licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 10µg for each component. The study lists 2 primary outcomes in all. 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 NCT00271479, which also lists 4 linked publications.
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 22 Dec 2006.