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

Purpose

HYPOTHESES:

That infants receiving PHiD-CV10 as a booster at 13 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.
That infants receiving PCV13 as a booster at 13 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.

Condition	Intervention	Phase
Otitis Media Febrile Illness Cough Lower Respiratory Tract Infection Upper Respiratory Tract Infection	Biological: Prevenar13 Biological: Synflorix	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-equivalence Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Pneumococcal Conjugate Vaccine (PCV) Schedules for the Northern Territory (NT): Randomised Controlled Trial of Booster Vaccines to Broaden and Strengthen Protection From Invasive and Mucosal Infections.

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:

Immune response [ Time Frame: At 18 months of age ] [ Designated as safety issue: No ]
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, 5 months after the booster dose. This will be determined in ELISA assays.

Secondary Outcome Measures:

Nasopharyngeal carriage [ Time Frame: At 13, 18 and 36 months of age ] [ Designated as safety issue: No ]
At baseline (13 mo), 18 and 36 months of age, the proportion of children with a any carriage of serotype 3, 6A and 19A pneumococci b any carriage of any NTHi
Otitis media [ Time Frame: At 13, 18 and 36 months of age ] [ Designated as safety issue: No ]
At baseline (13 mo), 18 and 36 months of age, the proportion of children with c any otitis media. d any tympanic membrane perforation

Other Outcome Measures:

Episodes of respiratory illness and acute otitis media [ Time Frame: Between baseline (13 mo) and 36 months of age ] [ Designated as safety issue: No ]
Between baseline (13 mo) and 36 months of age Episodes of respiratory illness and acute otitis media


Estimated Enrollment:	270
Study Start Date:	December 2012
Estimated Study Completion Date:	December 2018
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Prevenar13 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 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). Other Names: PCV13 Prevnar13
Experimental: Synflorix The booster vaccination schedule consists of one dose of 0.5 ml with an interval of at least 1 month between doses.	Biological: 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 Names: PHiD-CV PHiD-CV10

Arms

Assigned Interventions

Experimental: Prevenar13

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

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).

Other Names:

PCV13
Prevnar13

Experimental: Synflorix

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

Biological: 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 Names:

PHiD-CV
PHiD-CV10

Show Detailed Description

Eligibility


Ages Eligible for Study:	9 Months to 3 Years (Child)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

adverse reaction to Prevenar13 or Synflorix

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735084

Locations


Australia, Northern Territory
Menzies School of Health Research
Darwin, Northern Territory, Australia, 0810

Sponsors and Collaborators

Menzies School of Health Research

National Health and Medical Research Council, Australia

Investigators


Principal Investigator:	Amanda J Leach, PhD	Menzies School of Health Research

More Information

Publications:

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.

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.

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. Review.

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.

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.

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.

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.

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.

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.

Simell B, Nurkka A, Lahdenkari M, Givon-Lavi N, Käyhty 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.

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.

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.

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.


Responsible Party:	Menzies School of Health Research
ClinicalTrials.gov Identifier:	NCT01735084 History of Changes
Other Study ID Numbers:	1046999
Study First Received:	November 15, 2012
Last Updated:	September 22, 2015
Health Authority:	Australia: National Health and Medical Research Council Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Menzies School of Health Research:


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

Additional relevant MeSH terms:


Infection Communicable Diseases Respiratory Tract Infections Otitis Media Respiratory Tract Diseases Otitis	Ear Diseases Otorhinolaryngologic Diseases Vaccines Heptavalent Pneumococcal Conjugate Vaccine Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016

Using Pneumococcal Vaccines in Combination for Maximum Protection From Ear and Lung Infections in First 3 Years of Life (PREV-IX_B)