Pneumococcal Vaccines Early and in Combination

NCT01174849 | Completed Phase 4 DMC

• 2 other identifiers: 605810ACTRN12610000544077
• Study Type: interventional
• Target: 425
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Otitis Media

Keywords

otitis media; pneumococcal vaccines; randomised controlled trial; high-risk children; indigenous; Australia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• nasopharyngeal carriage

  7 months of age

• nasopharyngeal carriage

  7 months of age

• otitis media

  7 months of age

Study Arms (3)

Synflorix

ACTIVE COMPARATOR

Drug: Synflorix

Prevenar13

ACTIVE COMPARATOR

Drug: Prevenar13

COMBO

EXPERIMENTAL

COMBINATION SCHEDULE of comparator vaccine 1 and comparator vaccine 2 Synflorix at 1,2,4 months then Prevenar13 at 6 months.

Drug: COMBO

Interventions

Synflorix DRUG

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.

Also known as: PHiD-CV

Synflorix

Prevenar13 DRUG

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.

Also known as: PCV13

Prevenar13

COMBO DRUG

COMBINATION SCHEDULE of vaccine 1 and vaccine 2: Synflorix (PHiD-CV) at 1,2,4 months then Prevenar13 (PCV13) at 6 months of age.

Also known as: Combination schedule

COMBO

Eligibility Criteria

• Age: 28 Days - 38 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Indigenous infants
• 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.

You may not qualify if:

• Prior adverse reaction to pneumococcal conjugate vaccines according to Australian Immunization Handbook.
• Gestational age \< 32 weeks

Sponsors & Collaborators

• Menzies School of Health Research: lead

Study Sites (1)

Menzies School of Health Research

Darwin, Northern Territory, 0811, Australia

Location

Related Publications (15)

• 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. doi: 10.1186/1471-2431-5-27.

  PMID: 16033643 BACKGROUND

• 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. doi: 10.1097/INF.0b013e318154b238.

  PMID: 18049380 BACKGROUND

• 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. doi: 10.1186/1471-2431-8-23.

  PMID: 18513453 BACKGROUND

• 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. doi: 10.1016/j.vaccine.2008.05.012. Epub 2008 May 27.

  PMID: 18562052 BACKGROUND

• 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. doi: 10.1186/1471-2334-9-121.

  PMID: 19650933 BACKGROUND

• 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. doi: 10.1186/1471-2431-9-14.

  PMID: 19228431 BACKGROUND

• 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. doi: 10.1097/00006454-199411000-00009.

  PMID: 7845752 BACKGROUND

• 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. doi: 10.1186/1472-6815-6-10.

  PMID: 16686940 BACKGROUND

• 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. doi: 10.1097/INF.0b013e31815bb6c5.

  PMID: 18174871 BACKGROUND

• 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. doi: 10.1016/S0140-6736(06)68304-9.

  PMID: 16517274 BACKGROUND

• 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 Q Rep. 2008 Mar;32(1):18-30. doi: 10.33321/cdi.2008.32.3.

  PMID: 18522302 BACKGROUND

• Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland K, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Skull SA, Oguoma VM, Chatfield MD, Lehmann D, Brennan-Jones CG, Binks MJ, Licciardi PV, Andrews RM, Snelling T, Krause V, Carapetis J, Chang AB, Morris PS. Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules. PLoS Med. 2024 Jun 3;21(6):e1004375. doi: 10.1371/journal.pmed.1004375. eCollection 2024 Jun.

  PMID: 38829821 DERIVED

• Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Chatfield MD, Lehmann D, Binks M, Chang AB, Carapetis J, Krause V, Andrews R, Snelling T, Skull SA, Licciardi PV, Oguoma VM, Morris PS. Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials. Lancet Infect Dis. 2022 Sep;22(9):1374-1387. doi: 10.1016/S1473-3099(22)00272-9. Epub 2022 Jun 27.

  PMID: 35772449 DERIVED

• Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Wilson N, Arrowsmith B, Beissbarth J, Chatfield MD, Oguoma VM, Morris PS. Otitis media outcomes of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal conjugate vaccine schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial. BMC Pediatr. 2021 Mar 8;21(1):117. doi: 10.1186/s12887-021-02552-z.

  PMID: 33685411 DERIVED

• Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, Brown NJ, McIntyre P, Smith-Vaughan H, Skull S, Balloch A, Andrews R, Carapetis J, McDonnell J, Krause V, Morris PS. Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial. BMJ Open. 2015 Jan 16;5(1):e007247. doi: 10.1136/bmjopen-2014-007247.

  PMID: 25596202 DERIVED

MeSH Terms

Conditions

Otitis Media

Interventions

PHiD-CV vaccine; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Otitis; Ear Diseases; Otorhinolaryngologic Diseases

Study Officials

• Amanda J Leach, PhD

  Menzies School of Health Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 4, 2010
• Study Start: August 1, 2011
• Primary Completion: September 21, 2017
• Study Completion: March 15, 2018
• Last Updated: October 18, 2018

Record last verified: 2018-10

Locations

AU (1)