Evaluation of Effectiveness of GSK Biologicals' Pneumococcal Conjugate Vaccine 1024850A Against Invasive Disease (FinIP)

• ClinicalTrials.gov Identifier: NCT00861380
• Recruitment Status: Completed
• First Posted: March 13, 2009
• Results First Posted: September 25, 2020
• Last Update Posted: December 17, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: March 12, 2009
• First Posted Date: March 13, 2009
• Results First Submitted Date: April 14, 2017
• Results First Posted Date: September 25, 2020
• Last Update Posted Date: December 17, 2020
• Actual Study Start Date: May 4, 2009
• Actual Primary Completion Date: January 31, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 4, 2020)

• Person Year Rate as Regards Subjects With Culture-confirmed IPD Due to Any of the 10 Pneumococcal Vaccine Serotypes. In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) as regards subjects with culture-confirmed invasive pneumococcal disease (IPD) due to any of the pneumococcal vaccine serotypes was tabulated (vaccine pneumococcal serotypes = serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). PYAR was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate as Regards Subjects With Culture-confirmed IPD Due to Any of the 10 Pneumococcal Vaccine Serotypes. In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) as regards subjects with culture-confirmed invasive pneumococcal disease (IPD) due to any of the pneumococcal vaccine serotypes was tabulated (vaccine pneumococcal serotypes = serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). PYAR was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.

• Original Primary Outcome Measures (submitted: March 12, 2009): Occurrence of culture-confirmed pneumococcal invasive diseases due to any of the vaccines-related pneumococcal serotypes (in children starting vaccination within the first 7 months of life). [ Time Frame: From the administration of the first vaccine dose up to study end. ]

Current Secondary Outcome Measures (submitted: November 20, 2020)

• Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course (Till End of Blinded ID FU Period) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course (Till End of Blinded ID FU Period) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Probable Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata. Data were not collected regarding indirect effects.
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (=number of subjects with hospital-diagnosed pneumonia) divided by T (=sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia- In Children Starting Vaccination in the 7-11 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia - In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia With Chest X-ray (CXR) Reading According to WHO Criteria- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 7-11 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 12-18 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Tympanostomy Tube Placements- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination in the 7-11 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Antimicrobial Prescriptions- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months ]
  PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 7-11 Months Schedule [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
• Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population) [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months ]
  PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
• Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - mean FU time=24 months ]
  Antimicrobial susceptibility classification of IPD isolates reported during IPD follow-up with percentages for each serotype for the following categories: S= susceptible; I = intermediate ; R = resistant; N = not available.
• Number of Subjects With Lower Respiratory Tract Infections (LRTIs) (in a Subset of Subjects in Turku Area) [ Time Frame: From the administration of the first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (at least 30 months) ]
  Analysis of this outcome was performed in the Turku area. The number of subjects reporting at least one LRTI any time after the administration of the first vaccine dose was tabulated.
• Number of Subjects With Upper Respiratory Tract Infections (URTIs) (in a Subset of Subjects in Turku Area) [ Time Frame: From the administration of the first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (at least 30 months) ]
  Analysis of this outcome was performed in the Turku area. The number of subjects reporting at least one URTI any time after the administration of the first vaccine dose was tabulated.
• Number of Subjects With SAEs Reported During the Blinded Invasive Disease Phase, of the Study [ Time Frame: For Month 0 till the end of the blinded ID Follow-Up, (at least 30 months from study start) ]
  An event is defined as 'serious' when it meets one of the pre-defined outcomes described below: results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation; results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject. Medical or scientific judgement should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These should also be considered serious.
• Number of Subjects Enrolled and Vaccinated in the 10PN-PD-DIT-043 and 10PN-PD-DIT-053 Study With Post-study SAEs Reported Via Passive Surveillance- Subjects Enrolled Aged 6 Weeks to 6 Months and 7 to 18 Months [ Time Frame: From the end of the blinded ID Follow-Up period(at least 30 months from study start) up to the end of 18-month period after study unblinding ]
  An event is defined as 'serious' when it meets one of the pre-defined outcomes described below: results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation; results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject. Medical or scientific judgement should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These should also be considered serious.
• Culture-confirmed Invasive Disease (ID) Person Year Rate - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course Till End of LT FU Period [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the long-term Follow-up period (The Follow-up period lasted at least 77 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
• Culture-confirmed Invasive Disease (ID) Person Year Rate - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course Till End of LT FU Period [ Time Frame: Period of follow-up was any time after the administration of first vaccine dose till the end of the long-term Follow-up period (The Follow-up period lasted at least 77 months) ]
  The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.

Original Secondary Outcome Measures (submitted: March 12, 2009)

• Occurrence of culture-confirmed invasive diseases (ID) due to any bacterial pathogens (in all subjects) [ Time Frame: From the administration of the first vaccine dose up to study end. ]
• Occurrence of probable cases of ID caused by any bacterial pathogen (in all subjects) [ Time Frame: From the administration of the first vaccine dose up to study end. ]
• Occurrence of hospital-diagnosed pneumonia cases (in all subjects) [ Time Frame: From the administration of the first vaccine dose up to study end. ]
• Occurrence of tympanostomy tube placements (in all subjects) [ Time Frame: From the administration of the first vaccine dose up to study end. ]
• Occurrence of outpatient antibiotic prescriptions (in all subjects) [ Time Frame: From the administration of the first vaccine dose up to study end. ]
• Antimicrobial susceptibility of S. pneumoniae and H. influenzae isolated from invasive disease (in vaccinated children) [ Time Frame: From the administration of the first vaccine dose up to study end. ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Effectiveness of GSK Biologicals' Pneumococcal Conjugate Vaccine 1024850A Against Invasive Disease
• Official Title: Evaluation of Effectiveness of GSK Biologicals' Pneumococcal Conjugate Vaccine 1024850A Against Invasive Disease

Brief Summary

The aim of this study is to assess the effectiveness of GSK Biologicals' pneumococcal conjugate vaccine (GSK1024850A), administered according to different vaccination schedules, against invasive disease caused by S. pneumoniae or H. influenzae as well as vaccine impact on the occurrence of hospital-diagnosed pneumonia cases, tympanostomy tube placement and outpatient antimicrobial prescriptions.

This study will also explore vaccine impact on occurrence of respiratory tract infections (RTIs), including acute otitis media (AOM) in a subset of children in Turku area.

• Detailed Description: The protocol posting has been updated with regards to the enrolment of subjects and outcome measures following Protocol amendment 2, 22 August 2011.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• Infections, Streptococcal
• Streptococcus Pneumoniae

Intervention

• Biological: Pneumococcal conjugate vaccine GSK1024850A
  2, 3 or 4 Intramuscular injections, depending on the age at the time of first vaccination
• Biological: GSK Biologicals' Engerix TM vaccine (Hepatitis B vaccine)

  3 or 4 Intramuscular injections, depending on the age at the time of first vaccination.

  Control 3+1 and Control 2+1 groups, only for children < 12 months of age at the time of first study vaccination.

• Biological: GSK Biologicals' Havrix TM vaccine (Hepatitis A vaccine)
  2 Intramuscular injections. Control 3+1 and Control 2+1 groups, only for children >= 12 months of age at the time of first study vaccination.

Study Arms

• Experimental: 10Pn3+1-6W- 6M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.
  Intervention: Biological: Pneumococcal conjugate vaccine GSK1024850A
• Experimental: 10Pn2+1-6W-6M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.
  Intervention: Biological: Pneumococcal conjugate vaccine GSK1024850A
• Active Comparator: Ctrl-6W-6M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.
  Intervention: Biological: GSK Biologicals' Engerix TM vaccine (Hepatitis B vaccine)
• Experimental: 10Pn7-11M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
  Intervention: Biological: Pneumococcal conjugate vaccine GSK1024850A
• Active Comparator: Ctrl7-11M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
  Intervention: Biological: GSK Biologicals' Engerix TM vaccine (Hepatitis B vaccine)
• Experimental: 10Pn12-18M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
  Intervention: Biological: Pneumococcal conjugate vaccine GSK1024850A
• Active Comparator: Ctrl12-18M/043 Group
  Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
  Intervention: Biological: GSK Biologicals' Havrix TM vaccine (Hepatitis A vaccine)

Publications *

• Palmu AA, Jokinen J, Borys D, Nieminen H, Ruokokoski E, Siira L, Puumalainen T, Lommel P, Hezareh M, Moreira M, Schuerman L, Kilpi TM. Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial. Lancet. 2013 Jan 19;381(9862):214-22. doi: 10.1016/S0140-6736(12)61854-6. Epub 2012 Nov 16. Erratum In: Lancet. 2013 May 18;381(9879):1720. Lancet. 2015 May 30;385(9983):2152.
• Palmu AA, Jokinen J, Nieminen H, Rinta-Kokko H, Ruokokoski E, Puumalainen T, Borys D, Lommel P, Traskine M, Moreira M, Schuerman L, Kilpi TM. Effect of pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) on outpatient antimicrobial purchases: a double-blind, cluster randomised phase 3-4 trial. Lancet Infect Dis. 2014 Mar;14(3):205-12. doi: 10.1016/S1473-3099(13)70338-4. Epub 2013 Nov 26.
• Palmu AA, Jokinen J, Nieminen H, Syrjanen R, Ruokokoski E, Puumalainen T, Moreira M, Schuerman L, Borys D, Kilpi TM. Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial. Lancet Respir Med. 2014 Sep;2(9):717-27. doi: 10.1016/S2213-2600(14)70139-0. Epub 2014 Aug 7.
• Palmu AA, Jokinen J, Nieminen H, Rinta-Kokko H, Ruokokoski E, Puumalainen T, Traskine M, Moreira M, Borys D, Schuerman L, Kilpi TM. Effectiveness of the Ten-valent Pneumococcal Conjugate Vaccine Against Tympanostomy Tube Placements in a Cluster-randomized Trial. Pediatr Infect Dis J. 2015 Nov;34(11):1230-5. doi: 10.1097/INF.0000000000000857.
• Palmu AA, Jokinen J, Nieminen H, Rinta-Kokko H, Ruokokoski E, Puumalainen T, Moreira M, Schuerman L, Borys D, Kilpi TM. Vaccine-preventable disease incidence of pneumococcal conjugate vaccine in the Finnish invasive pneumococcal disease vaccine trial. Vaccine. 2018 Mar 27;36(14):1816-1822. doi: 10.1016/j.vaccine.2018.02.088.
• Nieminen H, Rinta-Kokko H, Jokinen J, Puumalainen T, Moreira M, Borys D, Schuerman L, Palmu AA. Effectiveness of the 10-valent pneumococcal conjugate vaccine among girls, boys, preterm and low-birth-weight infants - Results from a randomized, double-blind vaccine trial. Vaccine. 2019 Jun 19;37(28):3715-3721. doi: 10.1016/j.vaccine.2019.05.033. Epub 2019 May 20.
• Kilpi TM, Jokinen J, Puumalainen T, Nieminen H, Ruokokoski E, Rinta-Kokko H, Traskine M, Lommel P, Moreira M, Ruiz-Guinazu J, Borys D, Schuerman L, Palmu AA. Effectiveness of pneumococcal Haemophilus influenzae protein D conjugate vaccine against pneumonia in children: A cluster-randomised trial. Vaccine. 2018 Sep 18;36(39):5891-5901. doi: 10.1016/j.vaccine.2018.08.020. Epub 2018 Aug 23.
• Rinta-Kokko H, Palmu AA, Ruokokoski E, Nieminen H, Moreira M, Schuerman L, Borys D, Jokinen J. Evaluation of the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine in a cluster-randomised trial. PLoS One. 2022 Jan 5;17(1):e0261750. doi: 10.1371/journal.pone.0261750. eCollection 2022.
• Vesikari T, Forsten A, Seppa I, Kaijalainen T, Puumalainen T, Soininen A, Traskine M, Lommel P, Schoonbroodt S, Hezareh M, Moreira M, Borys D, Schuerman L. Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D-Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media-A Double-Blind Randomized Clinical Trial in Finland. J Pediatric Infect Dis Soc. 2016 Sep;5(3):237-248. doi: 10.1093/jpids/piw010. Epub 2016 Apr 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 11, 2013): 41188
• Original Estimated Enrollment (submitted: March 12, 2009): 91000
• Actual Study Completion Date: October 5, 2013
• Actual Primary Completion Date: January 31, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female between, and including, 6 weeks to 18 months of age at the time of the first vaccination.
• Written informed consent obtained from parent(s) or from the guardian(s) of the subject.

Exclusion Criteria:

• Previous vaccination with any registered, non-registered or investigational pneumococcal vaccine other than the study vaccine, or planned use during the study period. If a child belongs to a high risk group for pneumococcal infections for which a licensed pneumococcal conjugate vaccine is made locally available, the subject can not be enrolled in the study and should be referred to the specific immunization program.
• Previous vaccination against Hepatitis B virus with any registered, non-registered or investigational vaccine, or planned use of such a vaccine other than the study vaccine during the study period.
• Previous vaccination against Hepatitis A virus with any registered, non-registered or investigational vaccine, or planned use of such a vaccine other than the study vaccine during the study period.
• Known severe hypersensitivity to any component of the study vaccines, including neomycin.
• Any medical condition that would contraindicate the initiation of routine immunization outside a clinical trial context.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Weeks to 18 Months (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland

Administrative Information

• NCT Number: NCT00861380
• Other Study ID Numbers: 111442; 2008-005149-48 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: https://clinicalstudydatarequest.com/Posting.aspx?ID=261

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Study Director, GSK
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: November 2020