Using Pneumococcal Vaccines in Combination for Maximum Protection From Ear and Lung Infections in First 3 Years of Life

NCT01735084 | Completed Phase 4 DMC

• 1 other identifier: 1046999
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 1

Brief Summary

HYPOTHESES:

1. 1.That infants receiving PHiD-CV10 as a booster at 12 months of age, compared to controls having no PHiD-CV10 booster (i.e. standard PCV13), will have higher HiD antibody levels, lower carriage of NTHi, and less tympanic membrane perforation at 18 and 36 months of age.
2. 2.That infants receiving PCV13 as a booster at 12 months of age, compared to controls having no PCV13 (i.e. PHiD-CV10 booster) will have higher antibody levels to serotypes 3, 6A and 19A, less carriage of these serotypes, and less tympanic membrane perforation at 18 and 36 months of age.

Conditions

Otitis Media; Febrile Illness; Cough; Lower Respiratory Tract Infection; Upper Respiratory Tract Infection

Keywords

randomized controlled trial; pneumococcal conjugate vaccines; booster dose; immunogenicity; nasopharyngeal carriage; Australian Indigenous; pediatric

Outcome Measures

Primary Outcomes (1)

• Immune response

  The primary outcome will be the proportion of subjects with serotype-specific antibody above the level required for protection from IPD in each study group at 18 months of age, 6 months after the booster dose. This will be determined in ELISA assays.

  At 18 months of age

Secondary Outcomes (2)

• Nasopharyngeal carriage

  At 12, 18 and 36 months of age

• Otitis media

  At 12, 18 and 36 months of age

Other Outcomes (1)

• Episodes of respiratory illness and acute otitis media

  Between baseline (12 mo) and 36 months of age

Study Arms (2)

Prevenar13

EXPERIMENTAL

The booster dose of Prevenar13 is 0.5 mL given intramuscularly only, with care to avoid injection into or near nerves and blood vessels. The preferred sites are anterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in young children.

Biological: Prevenar13

Synflorix

EXPERIMENTAL

The booster vaccination schedule consists of one dose of 0.5 ml with an interval of at least 1 month between doses.

Biological: Synflorix

Interventions

Prevenar13 BIOLOGICAL

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).

Also known as: PCV13, Prevnar13

Prevenar13

Synflorix BIOLOGICAL

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, PHiD-CV10

Synflorix

Eligibility Criteria

• Age: 9 Months - 3 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Australian Indigenous infant who was a participant in PREV-IX\_COMBO trial of primary course pneumococcal conjugate vaccines, age at least 2 months post final dose of primary course. Signed informed consent.

You may not qualify if:

• adverse reaction to Prevenar13 or Synflorix

Sponsors & Collaborators

• Menzies School of Health Research: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Menzies School of Health Research

Darwin, Northern Territory, 0810, Australia

Location

Related Publications (16)

• Williams SR, Mernagh PJ, Lee MH, Tan JT. Changing epidemiology of invasive pneumococcal disease in Australian children after introduction of a 7-valent pneumococcal conjugate vaccine. Med J Aust. 2011 Feb 7;194(3):116-20. doi: 10.5694/j.1326-5377.2011.tb04192.x.

  PMID: 21299484 BACKGROUND

• Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine. Vaccine. 2011 Nov 15;29(49):9127-31. doi: 10.1016/j.vaccine.2011.09.112. Epub 2011 Oct 5.

  PMID: 21983361 BACKGROUND

• Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011 Dec 3;378(9807):1962-73. doi: 10.1016/S0140-6736(10)62225-8. Epub 2011 Apr 12.

  PMID: 21492929 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

• Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, Elvin L, Ensor KM, Hackell J, Siber G, Malinoski F, Madore D, Chang I, Kohberger R, Watson W, Austrian R, Edwards K. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J. 2000 Mar;19(3):187-95. doi: 10.1097/00006454-200003000-00003.

  PMID: 10749457 BACKGROUND

• Hare KM, Grimwood K, Leach AJ, Smith-Vaughan H, Torzillo PJ, Morris PS, Chang AB. Respiratory bacterial pathogens in the nasopharynx and lower airways of Australian indigenous children with bronchiectasis. J Pediatr. 2010 Dec;157(6):1001-5. doi: 10.1016/j.jpeds.2010.06.002. Epub 2010 Jul 24.

  PMID: 20656297 BACKGROUND

• Vesikari T, Karvonen A, Korhonen T, Karppa T, Sadeharju K, Fanic A, Dieussaert I, Schuerman L. Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus Influenzae Protein D Conjugate Vaccine when administered as catch-up vaccination to children 7 months to 5 years of age. Pediatr Infect Dis J. 2011 Aug;30(8):e130-41. doi: 10.1097/INF.0b013e31821d1790.

  PMID: 21540760 BACKGROUND

• Clucas DB, Carville KS, Connors C, Currie BJ, Carapetis JR, Andrews RM. Disease burden and health-care clinic attendances for young children in remote aboriginal communities of northern Australia. Bull World Health Organ. 2008 Apr;86(4):275-81. doi: 10.2471/blt.07.043034.

  PMID: 18438516 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

• Simell B, Nurkka A, Lahdenkari M, Givon-Lavi N, Kayhty H, Dagan R, Jokinen J. Association of serotype-specific antibody concentrations and functional antibody titers with subsequent pneumococcal carriage in toddlers immunized with a 9-valent pneumococcal conjugate vaccine. Clin Vaccine Immunol. 2012 Jan;19(1):96-9. doi: 10.1128/CVI.05369-11. Epub 2011 Nov 9.

  PMID: 22072724 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

• Prymula R, Kriz P, Kaliskova E, Pascal T, Poolman J, Schuerman L. Effect of vaccination with pneumococcal capsular polysaccharides conjugated to Haemophilus influenzae-derived protein D on nasopharyngeal carriage of Streptococcus pneumoniae and H. influenzae in children under 2 years of age. Vaccine. 2009 Dec 10;28(1):71-8. doi: 10.1016/j.vaccine.2009.09.113. Epub 2009 Oct 8.

  PMID: 19818722 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

• 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

• Oguoma VM, Wilson N, Mulholland K, Santosham M, Torzillo P, McIntyre P, Smith-Vaughan H, Balloch A, Chatfield M, Lehmann D, Binks MJ, Chang A, Carapetis J, Krause V, Andrews R, Snelling T, Licciardi P, Morris P, Leach AJ. 10-Valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine (PHiD-CV10) versus 13-valent pneumococcal conjugate vaccine (PCV13) as a booster dose to broaden and strengthen protection from otitis media (PREVIX_BOOST) in Australian Aboriginal children: study protocol for a randomised controlled trial. BMJ Open. 2020 May 24;10(5):e033511. doi: 10.1136/bmjopen-2019-033511.

  PMID: 32448790 DERIVED

MeSH Terms

Conditions

Otitis Media; Cough; Respiratory Tract Infections

Interventions

13-valent pneumococcal vaccine; PHiD-CV vaccine

Condition Hierarchy (Ancestors)

Otitis; Ear Diseases; Otorhinolaryngologic Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections

Study Officials

• Amanda J Leach, PhD

  Menzies School of Health Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2012
• First Posted: November 28, 2012
• Study Start: March 12, 2013
• Primary Completion: February 14, 2019
• Study Completion: October 3, 2019
• Last Updated: March 25, 2020

Record last verified: 2020-03

Locations

AU (1)