Pneumococcal Vaccines Early and in Combination - Full Text View

Purpose

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.

Condition	Intervention	Phase
Otitis Media	Drug: Synflorix Drug: Prevenar13 Drug: COMBO	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-equivalence Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Ear Infections

Drug Information available for: Heptavalent pneumococcal conjugate vaccine Pneumococcal Vaccines

U.S. FDA Resources

Further study details as provided by Menzies School of Health Research:

Primary Outcome Measures:

Immunogenicity [ Time Frame: 7 months of age ] [ Designated as safety issue: No ]
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)

Secondary Outcome Measures:

nasopharyngeal carriage [ Time Frame: 7 months of age ] [ Designated as safety issue: No ]
At 7 months of age, the proportion of children with any carriage of serotype 19A pneumococci
nasopharyngeal carriage [ Time Frame: 7 months of age ] [ Designated as safety issue: No ]
At 7 months of age, the proportion of children with any carriage of non-capsular H. influenzae.
otitis media [ Time Frame: 7 months of age ] [ Designated as safety issue: No ]
At 7 months of age, the proportion of children with any otitis media.

Estimated Enrollment:	425
Study Start Date:	August 2011
Estimated Study Completion Date:	June 2015
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Synflorix	Drug: Synflorix 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. Other Name: PHiD-CV
Active Comparator: Prevenar13	Drug: Prevenar13 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. Other Name: PCV13
Experimental: COMBO COMBINATION SCHEDULE of comparator vaccine 1 and comparator vaccine 2 Synflorix at 1,2,4 months then Prevenar13 at 6 months.	Drug: COMBO COMBINATION SCHEDULE of vaccine 1 and vaccine 2: Synflorix (PHiD-CV) at 1,2,4 months then Prevenar13 (PCV13) at 6 months of age. Other Name: Combination schedule

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 38 Days
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01174849

Contacts

Contact: Amanda J Leach, PhD

+61 8 89228649

amanda.leach@menzies.edu.au

Locations

Australia, Northern Territory
Menzies School of Health Research	Recruiting
Darwin, Northern Territory, Australia, 0811
Contact: Amanda J Leach, PhD +61 8 89228196 ext 28649 amanda.leach@menzies.edu.au
Principal Investigator: Amanda J Leach, PhD

Sponsors and Collaborators

Menzies School of Health Research

Investigators

Principal Investigator:

Amanda J Leach, PhD

Menzies School of Health Research

More Information

Publications:

Morris PS, Leach AJ, Silberberg P, Mellon G, Wilson C, Hamilton E, Beissbarth J. Otitis media in young Aboriginal children from remote communities in Northern and Central Australia: a cross-sectional survey. BMC Pediatr. 2005 Jul 20;5:27.

Leach AJ, Morris PS. The burden and outcome of respiratory tract infection in Australian and aboriginal children. Pediatr Infect Dis J. 2007 Oct;26(10 Suppl):S4-7.

Leach AJ, Morris PS, Mathews JD; Chronic Otitis Media Intervention Trial - One (COMIT1) group. Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: a randomized controlled trial. BMC Pediatr. 2008 Jun 2;8:23.

Leach AJ, Morris PS, Mackenzie G, McDonnell J, Balloch A, Carapetis J, Tang M. Immunogenicity for 16 serotypes of a unique schedule of pneumococcal vaccines in a high-risk population. Vaccine. 2008 Jul 23;26(31):3885-91. Epub 2008 May 27.

Leach AJ, Morris PS, McCallum GB, Wilson CA, Stubbs L, Beissbarth J, Jacups S, Hare K, Smith-Vaughan HC. Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001. BMC Infect Dis. 2009 Aug 4;9:121.

Mackenzie GA, Carapetis JR, Leach AJ, Morris PS. Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination. BMC Pediatr. 2009 Feb 19;9:14.

Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatr Infect Dis J. 1994 Nov;13(11):983-9.

Smith-Vaughan H, Byun R, Nadkarni M, Jacques NA, Hunter N, Halpin S, Morris PS, Leach AJ. Measuring nasal bacterial load and its association with otitis media. BMC Ear Nose Throat Disord. 2006 May 10;6:10.

Hare KM, Morris P, Smith-Vaughan H, Leach AJ. Random colony selection versus colony morphology for detection of multiple pneumococcal serotypes in nasopharyngeal swabs. Pediatr Infect Dis J. 2008 Feb;27(2):178-80.

Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, Kohl I, Lommel P, Poolman J, Prieels JP, Schuerman L. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006 Mar 4;367(9512):740-8.

Roche PW, Krause V, Cook H, Barralet J, Coleman D, Sweeny A, Fielding J, Giele C, Gilmour R, Holland R, Kampen R; Enhanced Invasive Pneumococcal Disease Surveillance Working Group; Brown M, Gilbert L, Hogg G, Murphy D; Pneumococcal Working Party of the Communicable Diseases Network Australia. Invasive pneumococcal disease in Australia, 2006. Commun Dis Intell. 2008 Mar;32(1):18-30.

Responsible Party:	Menzies School of Health Research
ClinicalTrials.gov Identifier:	NCT01174849 History of Changes
Other Study ID Numbers:	605810, ACTRN12610000544077
Study First Received:	August 2, 2010
Last Updated:	October 31, 2012
Health Authority:	Australia: Human Research Ethics Committee

Keywords provided by Menzies School of Health Research:

otitis media
pneumococcal vaccines
randomised controlled trial

high-risk children
indigenous
Australia

Additional relevant MeSH terms:

Otitis
Otitis Media
Ear Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on June 17, 2013

Pneumococcal Vaccines Early and in Combination (PREVIX_COMBO)