Neonatal immunisation with pneumoccal conjugate vaccines: immunogenicity and the generation memory (Kenya)

ISRCTN	ISRCTN52829313
DOI	https://doi.org/10.1186/ISRCTN52829313
Protocol serial number	WHO/RPC028
Sponsor	Kenya Medical Research Institute (Kenya)
Funder	World Health Organization (WHO)/Department of Immunisation, Vaccines and Biologicals (IVB) (Switzerland)

Submission date: 04/08/2004
Registration date: 22/09/2004
Last edited: 13/09/2007

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Thomas Cherian
Scientific

World Health Organization
20 Avenue Appia
Geneva-27
CH-1211
Switzerland

Email	cheriant@who.int

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Current hypothesis as of 13/09/2007: In Kenyan children under 2 years of age, 23% of deaths from invasive pneumococcal disease occur in the first 14 weeks of life. Expanded Programme on Immunisation (EPI) vaccines are administered at 6, 10 and 14 weeks. Earlier vaccination against pneumococcus may prevent deaths of very young infants. This study examines whether 7-valent Pneumococcal Conjugate Vaccine (PCV) given on the first 72 hours of life is safe and whether it provides an adequate immunological response, including development of immunological memory, when compared to a regime in which the first dose is given at 6 weeks. 300 children will be randomised to one of two regimes; PCV at birth (up to 72 hours), 10 and 14 weeks or PCV at 6, 10 and 14 weeks. The safety and basic immunogenicity data will be analysed after a first phase of 60 children and a further phase of 240 children will be recruited if the results are found to be satisfactory. Please note that the change to this hypothesis was made due to an initial protocol modification, where the 'birth' dose was amended from 24 hours to 72 hours. No other area of this trial was amended. Previous hypothesis: In Kenyan children under 2 years of age, 23% of deaths from invasive pneumococcal disease occur in the first 14 weeks of life. Expanded Programme on Immunisation (EPI) vaccines are administered at 6, 10 and 14 weeks. Earlier vaccination against pneumococcus may prevent deaths of very young infants. This study examines whether 7-valent Pneumococcal Conjugate Vaccine (PCV) given on the first day of life is safe and whether it provides an adequate immunological response, including development of immunological memory, when compared to a regime in which the first dose is given at 6 weeks. 300 children will be randomised to one of two regimes; PCV at birth, 10 and 14 weeks or PCV at 6, 10 and 14 weeks. The safety and basic immunogenicity data will be analysed after a first phase of 60 children and a further phase of 240 children will be recruited if the results are found to be satisfactory.
Ethics approval(s)	Ethics approval received from: 1. Kenya Medical Research Institute (KEMRI)/National Ethical Review Committee on the 27th October 2003 2. World Health Organization (WHO) Ethics Review Committee on the 18th September 2003 (renewed annually)
Health condition(s) or problem(s) studied	Pneumococcus/vaccines
Intervention	Infants will receive 7-valent conjugate pneumococcal vaccine (PCV7) at birth (up to 72 hours - see point mentioned in hypothesis above), 6 and 10 weeks (group 1) or at 6, 10 and 14 weeks (group 2) along with routine Expanded Program of Immunisation (EPI) vaccines. Infants in each group will be randomised to receive either PCV7 or 23-valent pneumococcal polysaccharide vaccine at 9 months of age. Blood will be collected for measurement of antibody response prior to vaccine, 4 weeks after the primary series and pre- and 4 weeks post-booster dose. All infants will have Nasopharyngeal (NP) swabs collected at 18 weeks and 9 months of age that will be cultured for pneumococcus.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Pneumococcal Conjugate Vaccine (PCV)
Primary outcome measure(s)	1. Clinical safety data in children vaccinated at birth compared to children vaccinated first at 6 weeks of life 2. Immunogenicity as measured by anti-capsular Immunoglobulin G (IgG) Enzyme-Linked Immuno-Sorbent Assay (ELISA) to serotypes in the vaccine, measured after a complete primary course at 18 weeks.
Key secondary outcome measure(s)	1. Immunogenicity as measured by anti-capsular IgG ELISA after one or two doses of vaccine, of which one was given at birth 2. Immunological memory measured as IgG response to a booster vaccine dose (either PCV or 1/5th dose pneumococcal polysaccharide vaccine with a 50% probability of each) at 36 weeks 3. Functional immune response to first vaccination at birth as measured by prevalence of nasopharyngeal colonisation with S. pneumoniae at 18 and 36 weeks 4. Interference with immune response to diphtheria and tetanus attributable to vaccination with PCV at birth as measured by diphtheria and tetanus antibody concentration at 18 weeks 5. Interference with immune response to measles vaccine given at 36 weeks measured by anti-measles antibodies at 37 weeks 6. Effect of (maternal) pre-existing pneumococcal, diphtheria and tetanus antibody levels at birth on immune response to the primary course of PCV, and Diphtheria Pertussis Tetanus (DPT) vaccine.
Completion date	31/10/2006

Eligibility

Participant type(s)	Patient
Age group	Child
Sex	All
Target sample size at registration	300
Key inclusion criteria	1. Healthy infants born to mothers tested human immunodeficiency virus (HIV) negative in the voluntary counselling and testing service 2. Not known to have congenital immune deficiency 3. Birth weight greater than 2500 g 4. Informed consent
Key exclusion criteria	1. Infants requiring ongoing hospitalisation after birth 2. Suspected immune deficiency 3. Participation in another clinical trial Any child who suffers a serious adverse event directly attributable to pneumococcal vaccination will be excluded from continued participation.
Date of first enrolment	01/11/2004
Date of final enrolment	31/10/2006

Locations

Countries of recruitment

Kenya
Switzerland

Study participating centre

World Health Organization

Geneva-27
CH-1211
Switzerland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan