Pneumococcal Vaccines Early and in Combination

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an early schedule of a combination of three doses of PHiD-CV and one dose of PCV13, is superior to three doses of either PCV13 or PHiD-CV.

Detailed Description
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Aboriginal children in the Northern Territory (NT) have high rates of otitis media caused by non-capsular H. influenzae (NCHi) and pneumococci. Pneumococcal conjugate vaccine has effectively reduced disease caused by the 7 serotypes. Rates of non-vaccine serotype otitis media (OM), particularly 19A is increasing, and NCHi continues to be a major pathogen in perforations. Parallels with pneumonia are highly probable in this population. Vaccines with expanded and early age protection are needed. In early 2009 GSK's pneumococcal H. influenzae protein D conjugate vaccine (PHiD-CV) was licensed in Australia. Compared to the current vaccine, 7PCV, this vaccine offers protection from pneumococcal serotypes 1, 5, 7F as well as NCHi (which is a primary pathogen of OM, and possibly pneumonia). However by 2010, a new generation of Wyeth's 7PCV, PCV13 will also be licensed in Australia. Compared to PHiD-CV this vaccine offers protection from additional serotypes 3, 6A and 19A, however it does not offer protection from NCHi infection. There is no empirical evidence to suggest that either vaccine will have superior clinical efficacy for otitis media or pneumonia in high-risk children. The novel combination strategy proposed for this trial has the potential to provide the best of both vaccines.

Official Title
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A Randomised Controlled Trial of Pneumococcal Conjugate Vaccines Synflorix and Prevenar13 in Sequence or Alone in High-risk Indigenous Infants (PREV-IX_COMBO): Immunogenicity, Carriage and Otitis Media Outcomes

Conditions
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Otitis Media

Intervention / Treatment
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* Drug: Synflorix
* Drug: Prevenar13
* Drug: COMBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Indigenous infants 4 to 6 weeks of age Living in remote communities that have provided signed Expressions of Interest in participating in PREV-IX_COMBO trial Intend to remain in their community until their baby is 7 months of age Eligible for routine vaccinations. Exclusion Criteria: Prior adverse reaction to pneumococcal conjugate vaccines according to Australian Immunization Handbook. Gestational age < 32 weeks

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 38 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Synflorix<br> | Drug: Synflorix<br>* The 10-valent vaccine contains 1 µg of purified capsular polysaccharide of pneumococcal serotypes 1, 5, 6B, 7F, 9V, 14, and 23F conjugated to protein D, 3 µg of serotype 4 conjugated to protein D, 3 µg of serotype 18C conjugated to tetanus toxoid and 3 µg of serotype 19F conjugated to diphtheria toxoid.<br>* Other names: PHiD-CV;|
| Active Comparator: Prevenar13<br> | Drug: Prevenar13<br>* The vaccine is a ready to use homogeneous white suspension for intramuscular injection, supplied as a pre-filled syringe. Active ingredients Each 0.5 mL dose contains: 2.2 μg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F 4.4 μg of pneumococcal purified capsular polysaccharides for serotype 6B. Each serotype is individually conjugated to non-toxic diphtheria CRM197 protein and adsorbed on aluminium phosphate (0.565 mg). CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-based medium.<br>* Other names: PCV13;|
| Experimental: COMBO<br>COMBINATION SCHEDULE of comparator vaccine 1 and comparator vaccine 2 Synflorix at 1,2,4 months then Prevenar13 at 6 months. | Drug: COMBO<br>* COMBINATION SCHEDULE of vaccine 1 and vaccine 2: Synflorix (PHiD-CV) at 1,2,4 months then Prevenar13 (PCV13) at 6 months of age.<br>* Other names: Combination schedule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | At 7 months of age, the overall and serotype specific (particularly serotype 19A and HiD) a IgG Geometric Mean Concentration (GMC) b proportion of children with IgG GMC above threshold (0.35 microg/mL) | 7 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| nasopharyngeal carriage | At 7 months of age, the proportion of children with any carriage of serotype 19A pneumococci | 7 months of age | 
| nasopharyngeal carriage | At 7 months of age, the proportion of children with any carriage of non-capsular H. influenzae. | 7 months of age | 
| otitis media | At 7 months of age, the proportion of children with any otitis media. | 7 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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otitis media, pneumococcal vaccines, randomised controlled trial, high-risk children, indigenous, Australia