Immunogenicity of 3+1 Versus 2+1 Schedule for PCV7

NCT02040402 | Completed Phase 4 DMC

• 1 other identifier: UW 09-024
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Pneumonia is one of the most prevalent diseases in infants and children. The incidence of pneumonia in children less than 5 years old is about 34-40 cases per 1000 in Europe and America and more than 2 million children die of pneumonia annually. It was reported that Streptococcus pneumoniae accounted for 13%-53% of lower respiratory tract infections in different age group of infants or children. In addition, 7%-9% of bacterial meningitis was due to Streptococcus pneumoniae infection. In addition, children infected with Streptococcus pneumoniae often transmit the pathogens to adult. As a result, it is evident that Streptococcus pneumoniae presents a heavy burden to paediatrics practice. Vaccination of 7-valent pneumococcal conjugate vaccines is effective in preventing Streptococcus pneumonia .Routine use of PCV7 in the US has rapidly reduced rates of invasive pneumococcal disease in children. The impact of the vaccine was noted within 1 year of introduction. According to Centre for Disease Control's (CDC) Active Bacterial Core Surveillance (ABCs) the incidence of invasive pneumococcal disease among children \<5 years dropped 75% from 1998/1999 to 2005; disease caused by vaccine-type strains fell 94% from 80 to 4.6 per 100,000. Currently there are two immunization schedules: manufacturer recommended the 3+1 schedule and many countries adopted a 3 dose schedule, either 3+0 or 2+1 schedules. In US, it is recommended to give three doses during infancy (scheduled at 2, 4, 6 month) plus one dose at 12-15 months (3+1 schedule). Since several studies have demonstrated that two doses may provide similar direct protection to three conjugate doses during infancy, it is recommended to give two doses during infancy plus a booster dose 12 months in some European countries including United Kingdom. In this trial, the immunogenicity of the 3+1 schedule and the 2+1 schedule of 7-valent pneumococcal conjugated vaccine in young infants will be compared.

Conditions

Infectious Disease

Keywords

Comparison of pneumococcal conjugated vaccine regimes

Outcome Measures

Primary Outcomes (1)

• Serological response in terms of geometric mean titres after the primary dose series and booster for the 2+1 and 3+1 schedules.

  An average of one month post vaccination

Secondary Outcomes (1)

• Proportion of infants with Immunoglobulin G concentrations above 0.35ug/ml to the 7 serotypes

  An average of one month post vaccination

Study Arms (2)

4-Dose Regimen

ACTIVE COMPARATOR

3+1 schedule of 7-valent pneumococcal conjugated vaccine: Infants who are randomized for 3+1 schedule will be administrated one dose of PCV7 at the age of 2 months old, 4months old and 6 months old. A booster dose will be administrated at the age of 12 months old. Infants will be followed up for 12-16 months starting from vaccination of first dose. There is no restriction on the use of other medications before or during the follow-up period.

Biological: 7-valent pneumococcal conjugated vaccine

3-Dose Regimen

ACTIVE COMPARATOR

2+1 schedule of 7-valent pneumococcal conjugated vaccine: Infants who are randomized for 2+1 schedule will be administrated with one dose of PCV7 at the age of 2 months old and 4months old. A booster dose will be administrated at the age of 12 months old. Infants will be followed up for 12-16 months starting from vaccination of first dose. There is no restriction on the use of other medications before or during the follow-up period.

Biological: 7-valent pneumococcal conjugated vaccine

Interventions

7-valent pneumococcal conjugated vaccine BIOLOGICAL

Pneumococcal vaccine 3+1 and 2+1 schedule comparison

3-Dose Regimen

Eligibility Criteria

• Age: 6 Weeks - 9 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Chinese infants born in Hong Kong

You may not qualify if:

• (i)Previous administration of PCV7 or other pneumococcal vaccines
• (ii)History of immunodeficiency
• (iii)Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment
• (iv)Malignancy, other than squamous cell or basal cell skin cancer
• (v)Autoimmune disease
• (vi)History of asthma or reactive airways disease
• (vii)Cardiovascular and pulmonary disorder, chronic metabolic disease (including diabetes), renal dysfunction or hemoglobinopathies requiring regular medical follow-up or hospitalization during the preceding year
• (viii)Use of immunosuppressive medication
• (ix)Receipt of blood products or immunoglobulin in the past 6 month

Sponsors & Collaborators

• The University of Hong Kong: lead
• The Society for the Relief of Disabled Children, Hong Kong: collaborator

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong, China

Location

Related Publications (25)

• Pneumococcal conjugate vaccine for childhood immunization--WHO position paper. Wkly Epidemiol Rec. 2007 Mar 23;82(12):93-104. No abstract available. English, French.

  PMID: 17380597 BACKGROUND

• Black RE, Morris SS, Bryce J. Where and why are 10 million children dying every year? Lancet. 2003 Jun 28;361(9376):2226-34. doi: 10.1016/S0140-6736(03)13779-8.

  PMID: 12842379 BACKGROUND

• Bryce J, Boschi-Pinto C, Shibuya K, Black RE; WHO Child Health Epidemiology Reference Group. WHO estimates of the causes of death in children. Lancet. 2005 Mar 26-Apr 1;365(9465):1147-52. doi: 10.1016/S0140-6736(05)71877-8.

  PMID: 15794969 BACKGROUND

• Goetghebuer T, West TE, Wermenbol V, Cadbury AL, Milligan P, Lloyd-Evans N, Adegbola RA, Mulholland EK, Greenwood BM, Weber MW. Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia. Trop Med Int Health. 2000 Mar;5(3):207-13. doi: 10.1046/j.1365-3156.2000.00535.x.

  PMID: 10747284 BACKGROUND

• Mera RM, Miller LA, Daniels JJ, Weil JG, White AR. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States over a 10-year period: Alexander Project. Diagn Microbiol Infect Dis. 2005 Mar;51(3):195-200. doi: 10.1016/j.diagmicrobio.2004.10.009.

  PMID: 15766606 BACKGROUND

• Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau C, Reingold A, Lefkowitz L, Cieslak PR, Cetron M, Zell ER, Jorgensen JH, Schuchat A; Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med. 2000 Dec 28;343(26):1917-24. doi: 10.1056/NEJM200012283432603.

  PMID: 11136262 BACKGROUND

• Kyaw MH, Lynfield R, Schaffner W, Craig AS, Hadler J, Reingold A, Thomas AR, Harrison LH, Bennett NM, Farley MM, Facklam RR, Jorgensen JH, Besser J, Zell ER, Schuchat A, Whitney CG; Active Bacterial Core Surveillance of the Emerging Infections Program Network. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl J Med. 2006 Apr 6;354(14):1455-63. doi: 10.1056/NEJMoa051642.

  PMID: 16598044 BACKGROUND

• Song JH, Lee NY, Ichiyama S, Yoshida R, Hirakata Y, Fu W, Chongthaleong A, Aswapokee N, Chiu CH, Lalitha MK, Thomas K, Perera J, Yee TT, Jamal F, Warsa UC, Vinh BX, Jacobs MR, Appelbaum PC, Pai CH. Spread of drug-resistant Streptococcus pneumoniae in Asian countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study. Clin Infect Dis. 1999 Jun;28(6):1206-11. doi: 10.1086/514783.

  PMID: 10451154 BACKGROUND

• Yao K, Shen X, Yul S, Lu Q, Deng L, Ye Q, Zhang H, Deng Q, Hu Y, Yang Y. Antimicrobial resistance and serotypes of nasopharyngeal strains of Streptococcus pneumoniae in Chinese children with acute respiratory infections. J Int Med Res. 2007 Mar-Apr;35(2):253-67. doi: 10.1177/147323000703500210.

  PMID: 17542413 BACKGROUND

• Murray D, Jackson C. A conjugate vaccine for the prevention of pediatric pneumococcal disease. Mil Med. 2002 Aug;167(8):671-7.

  PMID: 12188240 BACKGROUND

• Trotter CL, McVernon J, Ramsay ME, Whitney CG, Mulholland EK, Goldblatt D, Hombach J, Kieny MP; SAGE subgroup. Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae. Vaccine. 2008 Aug 18;26(35):4434-45. doi: 10.1016/j.vaccine.2008.05.073. Epub 2008 Jun 17.

  PMID: 18617296 BACKGROUND

• Trotter CL, Greenwood BM. Meningococcal carriage in the African meningitis belt. Lancet Infect Dis. 2007 Dec;7(12):797-803. doi: 10.1016/S1473-3099(07)70288-8.

  PMID: 18045562 BACKGROUND

• Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Reingold A, Cieslak PR, Pilishvili T, Jackson D, Facklam RR, Jorgensen JH, Schuchat A; Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003 May 1;348(18):1737-46. doi: 10.1056/NEJMoa022823.

  PMID: 12724479 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease--United States, 1998-2003. MMWR Morb Mortal Wkly Rep. 2005 Sep 16;54(36):893-7.

  PMID: 16163262 BACKGROUND

• Kaplan SL, Mason EO Jr, Wald ER, Schutze GE, Bradley JS, Tan TQ, Hoffman JA, Givner LB, Yogev R, Barson WJ. Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics. 2004 Mar;113(3 Pt 1):443-9. doi: 10.1542/peds.113.3.443.

  PMID: 14993532 BACKGROUND

• Kellner JD, Church DL, MacDonald J, Tyrrell GJ, Scheifele D. Progress in the prevention of pneumococcal infection. CMAJ. 2005 Nov 8;173(10):1149-51. doi: 10.1503/cmaj.051150. No abstract available.

  PMID: 16275962 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

• Mahon BE, Hsu K, Karumuri S, Kaplan SL, Mason EO Jr, Pelton SI; U.S. Pediatric Multicenter Pneumococcal Surveillance Group; Massachusetts Department of Public Health Epidemiologists. Effectiveness of abbreviated and delayed 7-valent pneumococcal conjugate vaccine dosing regimens. Vaccine. 2006 Mar 24;24(14):2514-20. doi: 10.1016/j.vaccine.2005.12.025. Epub 2005 Dec 27.

  PMID: 16417951 BACKGROUND

• Whitney CG, Pilishvili T, Farley MM, Schaffner W, Craig AS, Lynfield R, Nyquist AC, Gershman KA, Vazquez M, Bennett NM, Reingold A, Thomas A, Glode MP, Zell ER, Jorgensen JH, Beall B, Schuchat A. Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study. Lancet. 2006 Oct 28;368(9546):1495-502. doi: 10.1016/S0140-6736(06)69637-2.

  PMID: 17071283 BACKGROUND

• Poehling KA, Szilagyi PG, Grijalva CG, Martin SW, LaFleur B, Mitchel E, Barth RD, Nuorti JP, Griffin MR. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. 2007 Apr;119(4):707-15. doi: 10.1542/peds.2006-2138.

  PMID: 17403841 BACKGROUND

• Grijalva CG, Poehling KA, Nuorti JP, Zhu Y, Martin SW, Edwards KM, Griffin MR. National impact of universal childhood immunization with pneumococcal conjugate vaccine on outpatient medical care visits in the United States. Pediatrics. 2006 Sep;118(3):865-73. doi: 10.1542/peds.2006-0492.

  PMID: 16950975 BACKGROUND

• Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. 2007 Apr 7;369(9568):1179-86. doi: 10.1016/S0140-6736(07)60564-9.

  PMID: 17416262 BACKGROUND

• Esposito S, Lizioli A, Lastrico A, Begliatti E, Rognoni A, Tagliabue C, Cesati L, Carreri V, Principi N. Impact on respiratory tract infections of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months of age. Respir Res. 2007 Feb 21;8(1):12. doi: 10.1186/1465-9921-8-12.

  PMID: 17313667 BACKGROUND

• Goldblatt D, Southern J, Ashton L, Richmond P, Burbidge P, Tasevska J, Crowley-Luke A, Andrews N, Morris R, Borrow R, Cartwright K, Miller E. Immunogenicity and boosting after a reduced number of doses of a pneumococcal conjugate vaccine in infants and toddlers. Pediatr Infect Dis J. 2006 Apr;25(4):312-9. doi: 10.1097/01.inf.0000207483.60267.e7.

  PMID: 16567982 BACKGROUND

• Yu S, Yao K, Shen X, Zhang W, Liu X, Yang Y. Serogroup distribution and antimicrobial resistance of nasopharyngeal isolates of Streptococcus pneumoniae among Beijing children with upper respiratory infections (2000-2005). Eur J Clin Microbiol Infect Dis. 2008 Aug;27(8):649-55. doi: 10.1007/s10096-008-0481-y. Epub 2008 Mar 18.

  PMID: 18347822 BACKGROUND

MeSH Terms

Conditions

Communicable Diseases

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yu-lung LAU, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair Professor of Paediatrics

Study Record Dates

• First Submitted: December 19, 2013
• First Posted: January 20, 2014
• Study Start: February 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 20, 2014

Record last verified: 2014-01

Locations

CN (1)