A phase II, double-blind, randomised, controlled, dose ranging study to evaluate the safety, immunogenicity, dose response and schedule response of a meningococcal A conjugate vaccine administered concomitantly with local expanded program on immunisation (EPI) vaccines in healthy infants
| ISRCTN | ISRCTN82484612 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82484612 |
| Secondary identifying numbers | RPC258 |
- Submission date
- 06/08/2008
- Registration date
- 06/08/2008
- Last edited
- 05/03/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Meningitis is an infection that causes inflammation of the meninges (the protective lining that cover the brain and spinal cord). Meningitis can be bacterial or viral, but bacterial meningitis is far more serious. If bacterial meningitis is not treated in time, then it can cause severe brain damage and infect the blood (septicaemia) leading to death. In Africa, more than 90% of meningitis epidemics are caused by a bacterial variety commonly referred to as group A meningitis, which mainly affects children. Due to the widespread devastation this disease has caused, a vaccine has been produced for use against meningitis A in sub-Saharan Africa, known as MenAfriVac. An important part in the development of new vaccines is to measure how effective they are, and how long the immunity gained from them lasts for. This information provides useful information about vaccination programmes and schedules (i.e. if “booster” injections are needed). The aim of this study is to determine the safest dose of the MenAfriVac vaccine and whether it is more effective when given alone or with the recommended vaccines for children (EPI vaccines).
Who can participate?
Healthy children aged between 14 and 18 weeks, who have received all of the recommended (EPI) vaccines for their age.
What does the study involve?
Participants are randomly allocated into four groups. The first group receive doses of MenAfriVac at 14 weeks and 9 months of age, the second group receive a dose at 9 months of age, the third group receive a dose at 12 months of age and the fourth group only receives the recommended vaccines (EPI). After 28 days, a blood sample is taken so that the immunity against group A meningitis is measured.
What are the possible benefits and risks of participating?
There is no direct benefit of participating in the study, however if any of the children involved have any sudden illnesses, then this will be treated straight away. There are no notable risks of participating other than possible discomfort during blood tests.
Where is the study run from?
Navrongo Health Research Centre (Ghana)
When is the study starting and how long is it expected to run for?
August 2008 to December 2017
Who is funding the study?
Bill and Melinda Gates Foundation (USA)
Who is the main contact?
Dr Marie-Pierre Preziosi
preziosim@who.int
Contact information
Scientific
Initiative for Vaccine Research
World Health Organization (WHO)
20 Avenue Appia
Geneva-27
CH-1211
Switzerland
| Phone | +41 (0)22 791 3744 |
|---|---|
| preziosim@who.int |
Study information
| Study design | Phase II double-blind randomised dose-ranging controlled clinical study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A phase II, double-blind, randomised, controlled, dose ranging study to evaluate the safety, immunogenicity, dose response and schedule response of a meningococcal A conjugate vaccine administered concomitantly with local expanded program on immunisation (EPI) vaccines in healthy infants |
| Study objectives | The aim of this Phase II dose-ranging clinical study is to evaluate the safety and immunogenicity of three different formulations of the PsA-TT vaccine (2.5, 5 or 10 µg concentration of Men A polysaccharide). |
| Ethics approval(s) | 1. Western Institutional Review Board, 30/11/2007, ref: 1095050) 2. Ghana Health Service Ethical Review Committee, 12/06/2008, ref: GHS-ERC 01/1/08 3. Navrongo Health Research Centre Institutional Review Board, 07/07/2008, ref: NHRCIRB070 4. Food and Drugs Board (Ghana), 25/07/2008, ref: FDB/CT/803 |
| Health condition(s) or problem(s) studied | Bacterial meningitis |
| Intervention | All participants are given the Expanded Programme on Immunization (EPI) vaccines. OPV and Pentavalent DTwPHBVHib vaccines are given at 6 weeks (with completion of a 10 and 14 week schedule), a single dose of yellow fever and measles vaccine is administered at 9-12 months, and a booster of pentavalent DTwPHBVHib vaccine is given at 12-18 months. Participants are then randomly allocated into one of four groups: Group 1: EPI vaccines concomitantly with two doses of the study vaccine (PsA-TT) in infancy at 14 weeks and 9 months of age Group 2: EPI vaccines concomitantly with one single dose of the study vaccine (PsA-TT) in infancy at 9 months of age Group 3: EPI vaccines concomitantly with one single dose of the study vaccine (PsA-TT) in the first year of life at 12 months of age Group 4: EPI vaccines only |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | PsA-TT |
| Primary outcome measure | To compare the immunogenicity at 28 days after vaccination of range dosages of the PsA-TT vaccine, when administered to infants in a two-dose schedule at 14 weeks and 9 months of age concomitantly with EPI vaccines. |
| Secondary outcome measures | 1. Safety of range dosages of the PsA-TT vaccine, when administered to healthy infants in a two-dose schedule at 14 weeks and 9 months of age concomitantly with EPI vaccines (i.e. diphtheria, tetanus, whole cell pertussis, hepatitis B, Hib, and oral poliomyelitis at 14 weeks; measles and yellow fever at 9 months) 2. Immunogenicity of the EPI vaccines in all vaccines groups, when administered alone or concomitantly with the PsA-TT vaccine at 14 weeks, 9 months, and 12 months of age 3. Immunogenicity at 28 days, at 12 and 24 months (i.e. at 24 and 36 months of age) after a single dose of the PsA-TT vaccine administered at 12 months of age concomitantly with EPI vaccines |
| Overall study start date | 18/08/2008 |
| Completion date | 31/12/2012 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 14 Weeks |
| Upper age limit | 18 Weeks |
| Sex | Both |
| Target number of participants | Initial study: 1200, |
| Key inclusion criteria | 1. Aged 14 to 18 weeks old 2. Free of obvious health problems as established by medical history including physical examination and clinical judgment of the investigator 3. Guardian capable and willing to bring their child or to receive home visits for their child for all follow-up visits 4. Residence in the study area 5. Fully vaccinated according to the local EPI schedule (Bacillus Calmette-Guerin [BCG] and OPV at birth, two doses of diphtheria, tetanus, whole cell pertussis, haemophilus influenzae type B and hepatitis B virus [DTwPHibHBV] and OPV at 6 and 10 weeks of age) |
| Key exclusion criteria | 1. Previous vaccination against serogroup A Neisseria meningitidis 2. Known exposure to serogroup A N. meningitidis since birth 3. History of allergic disease or known hypersensitivity to any component of the study vaccines 4. History of serious adverse reactions following administration of vaccines included in the local program of immunisation 5. Administration of any vaccine other than EPI vaccines within 30 days prior to administration of study vaccines or planned vaccination during the first four weeks after the study vaccination 6. Use of any investigational or non-registered drug since birth 7. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period 8. Chronic administration (defined as more than 14 days) of immunosuppressant or other immune-modifying agents since birth (including systemic or inhaled corticosteroids, this means prednisone, or equivalent, greater than 0.5 mg/kg/day; topical steroids are allowed) 9. A family history of congenital or hereditary immunodeficiency 10. History of meningitis or seizures or any neurological disorder 11. Major congenital defects or serious chronic illness, including malnutrition (as per investigator's judgment). Minimum weight should be of 4 kg at the time of enrolment in the study (at 14 - 18 weeks of age). 12. Acute disease at the time of enrolment (acute disease is defined as the presence of a moderate or severe illness with or without fever) is a temporary exclusion 13. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination or laboratory tests, which in the opinion of the investigator, might interfere with the study objectives 14. Any condition or criteria that in the opinion of the investigator might compromise the well being of the subject or the compliance with study procedures or interfere with the outcome of the study 15. Non-residence in the study area or intent to move out within 2 years |
| Date of first enrolment | 18/08/2008 |
| Date of final enrolment | 31/12/2017 |
Locations
Countries of recruitment
- Ghana
Study participating centre
Navrongo
-
Ghana
Sponsor information
Research organisation
212/2, Hadapsar
Pune
411 028
India
| Phone | +91 (0)20 699 3900 |
|---|---|
| contact@seruminstitute.com | |
| Website | http://www.seruminstitute.com |
"ROR" |
https://ror.org/04jk2xb11 |
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2016 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Publication of the initial study is planned by 2016. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 15/11/2015 | Yes | No | |
| Results article | results | 15/11/2015 | Yes | No | |
| Results article | results | 15/11/2015 | Yes | No | |
| Results article | results | 15/11/2015 | Yes | No |
Editorial Notes
05/03/2019: Internal review.
31/08/2016: Publication references added.
28/10/2015: At the request of the trialist, the follow-up phase of the study has been registered separately and so has been removed from this record. The follow-up study record is available at: http://www.isrctn.com/ISRCTN10763234.
17/09/2015: There was a substantial update of this record in order to include details of a follow-up phase of the study. This included added extra information in the hypothesis, interventions, outcome measures, inclusion/exclusion criteria, ethics and sponsor details fields.
