Pneumococcal Vaccine Booster Study in Healthy Children 12-18 Mths Old Previously Primed With the Same Vaccines

Booster Vaccination Course With the Pneumococcal Vaccine GSK 1024850A, DTPw-HBV/Hib and OPV or IPV in Children Who Completed the Primary Vaccination Course in Study 107007

The purpose of this observer blind study is to assess the safety in terms of fever >39°C (rectal temperature) and the immunogenicity in terms of antibody response following a booster vaccination with pneumococcal vaccine GSK 1024850A at 12 to 18 months of age in children previously primed with the same vaccines including a pneumococcal conjugate vaccine co-administered with a diphtheria, tetanus, whole cell pertussis (DTPw)-combined vaccine and OPV or IPV vaccines. Subjects participating in this study should have received three doses of pneumococcal conjugate vaccine in the primary study.

This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00344318)

Study Overview

• Status: Completed
• Conditions: Infections, Streptococcal
• Intervention / Treatment: Biological: Synflorix; Biological: Tritanrix-HepB; Biological: Hiberix; Biological: Polio Sabin; Biological: Prevenar (Wyeth); Biological: Poliorix

Detailed Description

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007

• Study Type: Interventional
• Enrollment (Actual): 756
• Phase: Phase 3

Contacts and Locations

Study Locations

• Philippines
  • Muntinlupa, Philippines, 1781
    • GSK Investigational Site
• Poland
  • Gdansk, Poland, 80-394
    • GSK Investigational Site
  • Lodz, Poland, 91-347
    • GSK Investigational Site
  • Trzebnica, Poland, 55-100
    • GSK Investigational Site
  • Tuchola, Poland, 89-500
    • GSK Investigational Site
  • Wroclaw, Poland, 52-312
    • GSK Investigational Site
  • Wroclaw, Poland, 50345
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
• A male or female between, and including, 12-18 months of age at the time of the booster vaccination and who previously participated in study 107007 and received three doses of pneumococcal conjugate vaccine.
• Written informed consent obtained from the parent or guardian of the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

• Concurrently participating in another clinical study, at any time during the study period (active phase and extended safety follow-up), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within one month preceding the booster dose of study vaccines, or planned use during the entire study period
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the booster dose of study vaccines.
• Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting one month before the booster dose of study vaccines and up to the follow-up visit.
• Administration of any pneumococcal, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b vaccine other than the study vaccines from study 107007.
• History of, or intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b diseases.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
• History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease.
• Acute disease at the time of enrolment.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
• A family history of congenital or hereditary immunodeficiency.
• Major congenital defects or serious chronic illness.
• Administration of immunoglobulins and/or any blood products within three months preceding the booster dose of study vaccines or planned administration during the active phase of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synflorix + Tritanrix -HepB/ Hiberix + Polio Sabin Group; Subjects in the Philippines, primary vaccinated at 6-10-14 weeks of age, receiving booster dose of Synflorix™ vaccine, co-administered with Tritanrix™-HepB/ Hiberix™ and Polio Sabin™ vaccines at 12-18 months of age.	Biological: Synflorix; Intramuscular injection, 1 dose; Other Names: Pneumococcal conjugate vaccine GSK1024850A; Biological: Tritanrix-HepB; Intramuscular injection, 1 dose; Other Names: DTPw-HBV vaccine; Biological: Hiberix; Reconstituted with Tritanrix-Hep B before injection; Other Names: Hib vaccine; Biological: Polio Sabin; Oral, 1 dose; Other Names: OPV
Active Comparator: Prevenar + Tritanrix - HepB/ Hiberix + Polio Sabin Group; Subjects in the Philippines, primary vaccinated at 6-10-14 weeks of age, receiving booster dose of the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/ Hiberix™ and Polio Sabin™ at 12-18 months of age.	Biological: Tritanrix-HepB; Intramuscular injection, 1 dose; Other Names: DTPw-HBV vaccine; Biological: Hiberix; Reconstituted with Tritanrix-Hep B before injection; Other Names: Hib vaccine; Biological: Polio Sabin; Oral, 1 dose; Other Names: OPV; Biological: Prevenar (Wyeth); Intramuscular injection, 1 dose; Other Names: Pneumococcal conjugate vaccine
Experimental: Synflorix + Tritanrix -HepB/ Hiberix + Poliorix Group; Subjects in Poland, primary vaccinated at 2-4-6 months of age, receiving booster dose of Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 12-18 months of age.	Biological: Synflorix; Intramuscular injection, 1 dose; Other Names: Pneumococcal conjugate vaccine GSK1024850A; Biological: Tritanrix-HepB; Intramuscular injection, 1 dose; Other Names: DTPw-HBV vaccine; Biological: Hiberix; Reconstituted with Tritanrix-Hep B before injection; Other Names: Hib vaccine; Biological: Poliorix; Intramuscular injection, 1 dose; Other Names: IPV
Active Comparator: Prevenar + Tritanrix -HepB/ Hiberix + Poliorix Group; Subjects in Poland, primary vaccinated at 2-4-6 months of age, receiving booster dose of the Prevenar™ vaccine, co-administered with Tritanrix -HepB/ Hiberix and Poliorix™ at 12-18 months of age.	Biological: Tritanrix-HepB; Intramuscular injection, 1 dose; Other Names: DTPw-HBV vaccine; Biological: Hiberix; Reconstituted with Tritanrix-Hep B before injection; Other Names: Hib vaccine; Biological: Prevenar (Wyeth); Intramuscular injection, 1 dose; Other Names: Pneumococcal conjugate vaccine; Biological: Poliorix; Intramuscular injection, 1 dose; Other Names: IPV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Rectal Temperature Greater Than (>) the Cut-off	Fever was measured as rectal temperature. The cut-off was 39.0 degree Celsius (°C). Assessment of occurrences of fever > 39.0 (°C) was performed after booster vaccination with Synflorix™ or Prevenar™ vaccines.	Within the 4-day (Days 0-3) period after booster vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed included pain, redness and swelling. "Any" was defined as incidence of the specified symptom regardless of intensity. Grade 3 pain was defined as crying when limb was moved/ spontaneously painful. Grade 3 swelling/ redness was defined as swelling/ redness greater than (>) 30 millimeters (mm).	Within the 4-day (Days 0-3) period after booster vaccination
Number of Subjects With Any and Grade 3 Solicited General Symptoms	Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature greater than or equal to (≥) 38.0°C), irritability, and loss of appetite."Any" was defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Grade 3 drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectal temperature) >40.0 degree Celsius (°C). Grade 3 irritability was defined as crying that could not be comforted/ preventing normal activity. Grade 3 loss of appetite was defined as the subject not eating at all.	Within the 4-day (Days 0-3) period after booster vaccination
Number of Subjects With Unsolicited Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. "Any" was defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.	Within the 31-day (Days 0-30) period after booster vaccination
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity.	Throughout the active phase of the study (Month 0 to Month 1)
Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations ≥ the Cut-off	The cut-off was 0.20 microgram per milliliter (μg/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations	Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ 8.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Antibody Concentrations to Protein D (Anti-PD)	Seropositivity status, defined as anti-PD antibody concentrations ≥100 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A	Seropositivity status, defined as anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 microgram per milliliter (μg/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations ≥ the Cut-off	The cut-off of the assay was 0.05 μg/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ the Cut-off	The cut-off for the assay was 8.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A ≥ the Cut-off	The cut-of for the assay was 0.05 μg/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Opsonophagocytic Activity (OPA) Against Pneumococcal Cross-reactive Serotypes 6A and 19A ≥ the Cut-off	The cut-off for the assay was 8.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Antibody Concentrations Against Protein D (Anti-PD) ≥ the Cut-off	The cut-off for the assay was 100 ELISA units per milliliter (EL.U/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations	Seroprotection status, defined as anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 international units per milliliter (IU/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations	Seroprotection status, defined as anti-PRP antibody concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Anti-Bordetella Pertussis (BPT) Antibody Concentrations	Seropositivity status, defined as anti-BPT antibody concentrations ≥ 15 EL.U/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	Seroprotection status, defined as anti-HBs antibody concentrations ≥ 10 milli international units per milliliter (mIU/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Anti-polio Type 1, 2 and 3 Antibody Titers	Seroprotection status, defined as anti-polio type 1, anti-polio type 2 and anti-polio type 3 antibody titers ≥ 8.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-Bordetella Pertussis (BPT) With Concentrations ≥ the Cut-off	The cut-off for the assay was 15 EL.U/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-diphtheria (Anti-DT) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations ≥ the Cut-off	The cut-off for the assay was 0.1 milli-international units per milliliter (mIU/mL).	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration ≥ the Cut-off	The cut-off for the assay was 0.15 μg/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-PRP Antibody Concentration ≥ the Cut-off	The cut-off for the assay was 1.0 μg/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations ≥ the Cut-off	The cut-off for the assay was 10 mIU/mL.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers ≥ the Cut-off	The cut-off for the assay was 8.	Prior to (Month 0) and one month after booster vaccination (Month 1)
Number of Subjects With Vaccine Response to Anti-Bordetella Pertussis (BPT)	Vaccine response for anti-BPT, defined as the appearance of antibodies in subjects seronegative at pre-vaccination, or at least 2-fold increase of pre-vaccination antibody concentrations in those who were initially seropositive at pre-vaccination.	One month after booster vaccination (Month 1)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Schuerman L et al. Immune responses against cross-reactive pneumococcal serotypes 6A and 19A with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Immune responses to the non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) appear not influenced by co-administration with DTPw-combination vaccine. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Bermal N, Szenborn L, Edison A, Hernandez M, Pejcz J, Majda-Stanislawska E, Gatchalian S, Fanic A, Dieussaert I, Schuerman L. Safety and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine coadministered with DTPw-HBV/Hib and poliovirus vaccines. Pediatr Infect Dis J. 2011 Jan;30(1):69-72. doi: 10.1097/INF.0b013e3181f2da06.
• Bermal N et al. Primary and booster vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) co-administered with DTPw-HBV/Hib and polio vaccines. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Nancy B et al. Booster dose of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) administered to children in the Philippines: antibody responses and safety. Abstract presented at the 13th Asian Pacific Congress of Pediatrics (APCP). Shanghai, China, 14-18 October 2009.

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): October 22, 2007
• Primary Completion (Actual): May 10, 2008
• Study Completion (Actual): October 7, 2008

Study Registration Dates

• First Submitted: October 19, 2007
• First Submitted That Met QC Criteria: October 19, 2007
• First Posted (Estimate): October 22, 2007

Study Record Updates

• Last Update Posted (Actual): January 14, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Pneumococcal vaccine; Pneumococcal disease; Booster vaccination.
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 109509

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 109509
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register