Safety and Immunogenicity of 10-valent and 13-valent Pneumococcal Conjugate Vaccines in Papua New Guinean Children

Study Overview
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Brief Summary
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The study aims to evaluate the safety and immunogenicity of the 10-valent and 13-valent pneumococcal conjugate vaccines when administered in an accelerated schedule in Papua New Guinean children, who experience early dense upper respiratory tract colonisation with a broad range of pneumococcal serotypes, and to compare antibody titres following a booster dose of polysaccharide vaccine at 9 months with those children who received no booster at the same age.

Detailed Description
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The primary aim of the study is to determine whether PCV10 and PCV13 are safe and immunogenic in PNG infants for the serotypes in the respective vaccines. This study is important for the following reasons: There is a lack of data worldwide on immunogenicity in populations with very high early onset of dense URT carriage. The EPI immunisation schedule is very accelerated in PNG (ages 1,2 and 3 months). There are not data on functional antibody to PCVs in PNG. There are no data on NTHi Protein D antibody responses in PNG and worldwide in population with very high URT carriage rates from a young age, i.e. those most likely to benefit from a vaccine including NTHi protein carrier. It is important to investigate impact of vaccine on carriage density in view of our finding of limited impact of 7vPCV on URT carriage. There is no data on antibody responses following 10v or 13v PCV to booster with PPV as young as 9 months of age (which would be the most appropriate within the current PNG EPI schedule and in the many other third world countries). There is no data on antibody responses (including functional assays) to 23vPPV challenge at age 2 years after 23vPPV booster at age 9 months in children primed with PCV. The broad range of serotypes causing IPD in PNG necessitates continuing consideration of 23vPPV as a potential booster at age 9 months. Serotype-specific B cell memory is an important aspect that we can now test to address immunological safety of PPV in children primed with PCV. The Global Alliance for Vaccines and Immunisation (GAVI) and the World Health Organisation (WHO) have committed to the introduction of PCV for infants in GAVI-eligible countries (including PNG) using novel funding mechanism. In PNG, the introduction of a PCV is planned for 2013.

Official Title
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A Study of Safety and Immunogenicity of 10-valent and 13-valent Pneumococcal Conjugate Vaccines to Inform Policy Regarding Pneumococcal Vaccination of Papua New Guinean Children

Conditions
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Pneumonia, Meningitis, Bacteraemia, Sepsis, Otitis Media

Intervention / Treatment
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* Biological: Prevenar 13 and Synflorix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Health infants between 28 - 35 days old Exclusion Criteria: Infants of women not intending to remain in the are for at least two years Birth weigh < 2000 g (2kg) Severe congenital abnormalities Mother or child known to be HIV positive

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 35 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Synflorix or PCV10<br>130 children will receive Synflorix at 1-2-3 months | Biological: Prevenar 13 and Synflorix<br>* 260 children will be randomized to receive either Prevenar 13 or Synflorix at 1-2-3 months. At 9 months 65 children in the Prevenar 13 arm and 65 children in the Synflorix arm will receive booster dose of Pneumovax and at 23 months all children will receive a micro dose of Pneumovax.Blood will be collected at 1, 4, 9, 10, 23 and 24 months to determine serotype-specific antibody responses. Nasopharyngeal swabs will also be collected to measure carriage of pneumococci and non-typeable Haemophilus influenzae.<br>* Other names: Prevenar 13(R), PCV13;|
| Other: Prevenar 13<br>130 children will receive Prevenar 13 at 1-2-3 months | Biological: Prevenar 13 and Synflorix<br>* 260 children will be randomized to receive either Prevenar 13 or Synflorix at 1-2-3 months. At 9 months 65 children in the Prevenar 13 arm and 65 children in the Synflorix arm will receive booster dose of Pneumovax and at 23 months all children will receive a micro dose of Pneumovax.Blood will be collected at 1, 4, 9, 10, 23 and 24 months to determine serotype-specific antibody responses. Nasopharyngeal swabs will also be collected to measure carriage of pneumococci and non-typeable Haemophilus influenzae.<br>* Other names: Prevenar 13(R), PCV13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children with serotype-specific IgG concentration >= 0.35ug/ml at 4 and 9 months of age for 90% of PCV vaccine serotypes and proportion of children with OPA >=1:8 titres at 4, 10 and 24 months | IgG concentration to vaccine serotypes are >= 0.35ug/ml post-dose 3 at 4 and 9 months. Serotype-specific IgG concentration >=0.35ug/ml is protective level against invasive pneumococcal diseases. Opsonophagocytic titre of >=1:8 examined at 4, 10 and 24 months will inform on functional antibodies induced by vaccination. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare antibody concentrations to pneumococcal and Haemophilus influenzae protein antigens. | Measure antibody titres to surface proteins of pneumococci and Hi including Hi protein D, the carrier protein in PCV10 (Synflorix). | 2 years | 
| Determine carriage rates and bacterial load of pneumococci and H.influenzae | Proportion of carriage before and after vaccination will be measured using conventional culture methods. Bacterial load will be measured using PCR to determine impact of vaccines | 3 years | 
| Determine rates of hospital admission for acute respiratory tract infections at 9 and 23 months | Admissions and morbidity for acute respiratory tract infections will be documented at 9 and 23 months. | 2 yrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumococcal, vaccine, papua new guinea