Primary and Booster Vaccination Study With Pneumococcal Vaccine GSK1024850A in Healthy Japanese Children

Immunogenicity, Safety and Reactogenicity of GlaxoSmithKline Biologicals' Pneumococcal Vaccine GSK1024850A Following Primary and Booster Vaccination of Healthy Japanese Children

This study will aim to evaluate the immunogenicity, safety and reactogenicity of GlaxoSmithKline Biologicals' 10-valent pneumococcal conjugate vaccine GSK1024850A when co-administered with Japanese DTPa vaccine as a 3-dose primary immunization course in healthy Japanese children at 3, 4 and 5 months of age and as a booster vaccination at 17-19 months of age.

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Pneumococcal vaccine GSK1024850A; Biological: DTPa

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 451-0052
    • GSK Investigational Site
  • Chiba, Japan, 299-4503
    • GSK Investigational Site
  • Hiroshima, Japan, 720-8520
    • GSK Investigational Site
  • Hiroshima, Japan, 730-8562
    • GSK Investigational Site
  • Hokkaido, Japan, 003-0021
    • GSK Investigational Site
  • Kagawa, Japan, 765-8501
    • GSK Investigational Site
  • Kanagawa, Japan, 247-8533
    • GSK Investigational Site
  • Kanagawa, Japan, 243-8551
    • GSK Investigational Site
  • Kanagawa, Japan, 238-8567
    • GSK Investigational Site
  • Nagasaki, Japan, 856-8562
    • GSK Investigational Site
  • Niigata, Japan, 957-8588
    • GSK Investigational Site
  • Okayama, Japan, 701-0205
    • GSK Investigational Site
  • Osaka, Japan, 555-0001
    • GSK Investigational Site
  • Osaka, Japan, 591-8025
    • GSK Investigational Site
  • Osaka, Japan, 560-0004
    • GSK Investigational Site
  • Tokyo, Japan, 152-0021
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator/co-investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR(s)) can and will comply with the requirements of the protocol.
• A male or female between, and including, 90 and 118 days of age (3 months) at the time of the first vaccination.
• Written informed consent obtained from the parent(s)/LAR(s) of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Born after a gestation period of 36 to 42 weeks inclusive.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine(s), or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
• Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before the first dose of study vaccine(s) and ending on the last study visit, with the exception of Haemophilus influenzae type b vaccine, Hepatitis B Vaccine, Bacille Calmette-Guérin vaccine, Oral Polio Vaccine, Japanese encephalitis, measles and rubella, varicella, mumps, and flu vaccines.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Administration of any pneumococcal vaccine since birth except for the DTPa group for whom vaccination with a licensed pneumococcal vaccine by catch-up schedule will be allowed only if the 2 vaccine doses are administered between Study Visit 4 and 5, i.e. from the second blood sampling timepoint (Visit 4) onwards and up to 7 days before the booster dose of the DTPa vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of, or intercurrent diphtheria, tetanus, pertussis disease.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines.
• Major congenital defects or serious chronic illness.
• History of any seizures or progressive neurological disease.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
• Child in care.
• Acute disease and/or fever at the time of enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10Pn Group; Healthy male or female subjects, between 90 and 118 days of age who received 3 doses of Synflorix (10Pn) vaccine, administered intramuscularly on alternating (left/right) sides of the anterolateral thigh and DPT "KAKETSUKEN" Syringe (DTPa) vaccine administered subcutaneously on alternating (left/right) sides of the distal one third of the upper arm. Both vaccines were administered at 3, 4, and 5 months of age, followed by a booster dose at 17-19 months of age.	Biological: Pneumococcal vaccine GSK1024850A; Intramuscular injection, 4 doses; Other Names: Synflorix; Biological: DTPa; Subcutaneous injection, 4 doses; Other Names: DPT "KAKETSUKEN" Syringe
Active Comparator: DTPa Group; Healthy male or female subjects, between 90 and 118 days of age who received 3 doses of the DPT "KAKETSUKEN" Syringe (DTPa) vaccine, administered subcutaneously on alternating (left/right) sides of the distal one third of the upper arm at 3, 4, and 5 months of age, followed by a booster dose at 17-19 months of age.	Biological: DTPa; Subcutaneous injection, 4 doses; Other Names: DPT "KAKETSUKEN" Syringe

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes (Primary Immunization)	Concentrations were expressed as geometric mean concentrations (GMCs). Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 microgram per milliliter (µg/mL).	1 month following primary immunization (at Month 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes (Booster Immunization)	Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F ELISA, expressed as GMCs, in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. Antibody concentrations < 0.05 μg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group.	Prior to (PRE, at Month 14-16 ) and one month after booster (POST, at Month 15-17) immunization
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes (Primary Immunization)	Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	1 month following primary immunization (at Month 3)
Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes (Booster Immunization)	Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group.	Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Primary Immunization)	Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	1 month following primary immunization (at Month 3)
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Booster Immunization)	Concentrations were given in microgram per millilitre (µg/mL) and were expressed in geometric mean antibody concentrations. Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations < 0.05 g/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group.	Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization
Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Primary Immunization)	Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.	1 month following primary immunization (at Month 3)
Opsonophagocytic Titers Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Booster Immunization)	Cross-reactive pneumococcal vaccine serotypes assessed were 6A and 19A and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. Administration of catch-up pneumococcal vaccination with a licensed product other than Synflorix was allowed in the DTPa Group at least 7 days before DTPa vaccine booster dose. Thus, for this booster phase analysis, the DTPa Group was further split in DTPa + Prevenar Group and DTPa - no Prevenar Group.	Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization
Concentrations of Antibodies Against Protein D (PD) (Primary Immunization)	Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	1 month following primary immunization (at Month 3)
Concentrations of Antibodies Against Protein D (PD) (Booster Immunization)	Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.	Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization
Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT)(Primary Immunization)	Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per millilitre (IU/mL). Seroprotection status, defined as Anti-DT or Anti-TT antibody concentration equal to or greater than 0.1 IU/mL.	1 month following primary immunization (at Month 3)
Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT)(Booster Immunization)	Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per millilitre (IU/mL). Seroprotection status, defined as Anti-DT or Anti-TT antibody concentration equal to or greater than 0.1 IU/mL.	Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization
Concentrations of Antibodies Against Pertussis (PT) and Filamentous Haemagglutinin (FHA)(Primary Immunization)	Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per millilitre (EL.U/mL). Seropositivity was defined as an antibody concentration equal to or greater than 5 EL.U/mL	1 month following primary immunization (at Month 3)
Concentrations of Antibodies Against Pertussis (PT) and Filamentous Haemagglutinin (FHA)(Booster Immunization)	Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per millilitre (EL.U/mL). Seropositivity was defined as an antibody concentration equal to or greater than 5 EL.U/mL	Prior to (PRE, at Month 14-16) and one month after booster (POST, at Month 15-17) immunization
Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Primary Vaccination	Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.	During the 8-day (Days 0-7) after each primary vaccine dose
Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Booster Vaccination	Solicited local AEs assessed were pain, redness and swelling. Any = incidence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling above 30 millimetre.	During the 8-day (Days 0-7) period following booster vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Primary Vaccination	General AEs = drowsiness, fever (axillary ≥ 37.5 degrees Celsius), irritabilityand loss of appetite, vomiting. Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = > 39.5°C Related = symptom assessed by the investigator as related to the vaccination.	During the 8-day (Days 0-7) after each primary vaccine dose
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Booster Vaccination	Solicited general AEs = drowsiness, irritability, loss of appetite and fever (axillary ≥ 37.5 degrees Celsius). Any= Incidence of any symptom regardless of intensity grade or relationship to vaccination. Grade 3: drowsiness = prevented normal activity. irritability = crying that could not be comforted/ prevented normal activity. loss of appetite = not eating at all. Fever = temperature > 39.5°C Related = symptom assessed by the investigator as related to the vaccination.	During the 8-day (Days 0-7) period following booster vaccination
Number of Subjects With Unsolicited AEs After Primary Vaccination	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.	Within the 31-day (Days 0-30) post-primary vaccination period, across doses
Number of Subjects With Unsolicited AEs After Booster Vaccination	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.	Within the 31-day (Days 0-30) post booster vaccination period
Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.	From study start at Month 0 up to study end at Month 15-17

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Iwata S, Kawamura N, Kuroki H, Tokoeda Y, Miyazu M, Iwai A, Oishi T, Sato T, Suyama A, Francois N, Shafi F, Ruiz-Guinazu J, Borys D. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study. Hum Vaccin Immunother. 2015;11(4):826-37. doi: 10.1080/21645515.2015.1012019.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2009
• Primary Completion (Actual): August 13, 2010
• Study Completion (Actual): September 17, 2011

Study Registration Dates

• First Submitted: December 7, 2009
• First Submitted That Met QC Criteria: December 7, 2009
• First Posted (Estimate): December 9, 2009

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Booster vaccination; Pneumococcal disease; Primary vaccination
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 112640; 2011-003710-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Study Protocol
   Information identifier: 112640
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112640
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 112640
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 112640
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 112640
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 112640
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register