Pneumococcal Vaccines Early and in Combination

NCT ID: NCT01174849

Last Updated: 2018-10-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

425 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2018-03-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Otitis Media

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Synflorix

Group Type ACTIVE_COMPARATOR

Synflorix

Intervention Type 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.

Prevenar13

Group Type ACTIVE_COMPARATOR

Prevenar13

Intervention Type 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.

COMBO

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

Group Type EXPERIMENTAL

COMBO

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

PHiD-CV PCV13 Combination schedule

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

28 Days

Maximum Eligible Age

38 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Menzies School of Health Research

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Amanda J Leach, PhD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Menzies School of Health Research

Darwin, Northern Territory, Australia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 16033643 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18049380 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18513453 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18562052 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19650933 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19228431 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7845752 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16686940 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18174871 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16517274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18522302 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38829821 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35772449 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33685411 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25596202 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ACTRN12610000544077

Identifier Type: REGISTRY

Identifier Source: secondary_id

605810

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.