Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' 10-valent Pneumococcal Conjugate Vaccine

Phase 3

Completed

• Conditions: Infections, Streptococcal
• Interventions: Biological: Prevenar; Biological: Pneumococcal conjugate vaccine GSK1024850A; Biological: Tritanrix-HepB; Biological: Hiberix; Biological: Polio Sabin.; Biological: Poliorix.

• Registration Number: NCT00344318
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This study will evaluate safety, reactogenicity and immunogenicity of GSK Biologicals' pneumococcal conjugate vaccine compared to Prevenar™ when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines, according to 2 different schedules: 6-10-14 weeks or 2-4-6 months of age.

The study has 2 groups.

* One group of subjects will receive a 3-dose primary vaccination with the GSK Biologicals' pneumococcal conjugate vaccine (three different lots will be used and randomly allocated).

* The 2nd group of subjects will receive a 3-dose primary vaccination with Prevenar™.

All children will receive concomitantly DTPw-HBV/Hib and OPV or IPV vaccines. This protocol posting deals with objectives \& outcome measures of the primary study. The objectives \& outcome measures of the Booster study are presented in a separate protocol posting (NCT number =00547248).

Detailed Description

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

Study Timeline

• Study First Submitted: 2006-06-23
• Study First Submitted QC: 2006-06-23
• Study First Posted: 2006-06-26
• Study Start: 2006-08-07
• Primary Completion: 2007-04-27
• Study Completion: 2007-10-17
• Results First Submitted: 2017-08-31
• Status Verified: 2018-05
• Results First Submitted QC: 2018-05-16
• Last Update Submitted: 2018-05-16
• Results First Posted: 2018-12-07
• Last Update Posted: 2018-12-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 806

Inclusion Criteria

• Male or female between, and including, 6-12 weeks (42 to 90 days) of age at the time of the first vaccination.
• Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol
• 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.
• Born after a gestation period between 36 and 42 weeks.

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Exclusion Criteria

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before each dose of vaccine(s) and ending 7 days after dose 1 and dose 2 or 1 month after dose 3.
• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, and/or S. pneumoniae with the exception of vaccines where the first dose can be given within the first two weeks of life according to the national recommendations
• History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, and 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 neurological disease.
• Acute disease at the time of enrolment
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical
• A family history of congenital or hereditary immunodeficiency.
• Major congenital defects or serious chronic illness.
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the active phase of the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prevenar 1 Group	Tritanrix-HepB	Subjects aged 6-12 weeks from the Philippines receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ at 6, 10, 14 weeks of age.
Synflorix 2 Group	Poliorix.	Subjects aged 6-12 weeks from Poland receiving Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 2, 4, 6 months of age.
Synflorix 2 Group	Polio Sabin.	Subjects aged 6-12 weeks from Poland receiving Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 2, 4, 6 months of age.
Prevenar 1 Group	Prevenar	Subjects aged 6-12 weeks from the Philippines receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ at 6, 10, 14 weeks of age.
Prevenar 1 Group	Poliorix.	Subjects aged 6-12 weeks from the Philippines receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ at 6, 10, 14 weeks of age.
Synflorix 1 Group	Pneumococcal conjugate vaccine GSK1024850A	Subjects aged 6-12 weeks from the Philippines receiving Synflorix™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ vaccines at 6, 10, 14 weeks of age.
Synflorix 1 Group	Tritanrix-HepB	Subjects aged 6-12 weeks from the Philippines receiving Synflorix™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ vaccines at 6, 10, 14 weeks of age.
Synflorix 1 Group	Hiberix	Subjects aged 6-12 weeks from the Philippines receiving Synflorix™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ vaccines at 6, 10, 14 weeks of age.
Synflorix 1 Group	Polio Sabin.	Subjects aged 6-12 weeks from the Philippines receiving Synflorix™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ vaccines at 6, 10, 14 weeks of age.
Prevenar 1 Group	Hiberix	Subjects aged 6-12 weeks from the Philippines receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ at 6, 10, 14 weeks of age.
Prevenar 2 Group	Tritanrix-HepB	Subjects aged 6-12 weeks from Poland receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ at 2, 4, 6 months of age.
Synflorix 1 Group	Poliorix.	Subjects aged 6-12 weeks from the Philippines receiving Synflorix™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ vaccines at 6, 10, 14 weeks of age.
Synflorix 2 Group	Pneumococcal conjugate vaccine GSK1024850A	Subjects aged 6-12 weeks from Poland receiving Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 2, 4, 6 months of age.
Synflorix 2 Group	Hiberix	Subjects aged 6-12 weeks from Poland receiving Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 2, 4, 6 months of age.
Prevenar 2 Group	Poliorix.	Subjects aged 6-12 weeks from Poland receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ at 2, 4, 6 months of age.
Synflorix 2 Group	Tritanrix-HepB	Subjects aged 6-12 weeks from Poland receiving Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 2, 4, 6 months of age.
Prevenar 1 Group	Polio Sabin.	Subjects aged 6-12 weeks from the Philippines receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ at 6, 10, 14 weeks of age.
Prevenar 2 Group	Prevenar	Subjects aged 6-12 weeks from Poland receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ at 2, 4, 6 months of age.
Prevenar 2 Group	Hiberix	Subjects aged 6-12 weeks from Poland receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ at 2, 4, 6 months of age.
Prevenar 2 Group	Polio Sabin.	Subjects aged 6-12 weeks from Poland receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ at 2, 4, 6 months of age.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Reporting Rectal Temperature Above (>) 39.0 Degrees Celsius (°C)	Within 4 day (Days 0-3) after each dose and across doses	Fever was measured as rectal temperature. Assessment of occurrences of fever \> 39.0 °C was performed post doses 1, 2 and 3 and across doses of Synflorix™ or Prevenar™ vaccine.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms	Within 4 day (Days 0-3) after each dose and across doses	Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/spontaneously painful. Grade 3 swelling/redness was defined as swelling/redness larger than (\>) 30 millimeters (mm). "Any" is defined as incidence of the specified symptom regardless of intensity.
Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ 8
Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes 6A and 19A	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8
Number of Subjects With Concentrations of Antibodies Against Protein D (Anti-PD) Equal to or Above (≥) 100 ELISA Units Per Milliliter (EL.U/mL)	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Cut-off values assessed were greater than or equal to 100 ELISA units per milliliter (EL.U/mL) in the sera of subjects.
Number of Subjects With Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations Equal to or Above 15 ELISA Unit Per Milli-liter (EL.U/mL) (Seropositivity)	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Cut-off values assessed were greater than or equal to 15 ELISA unit per milli-liter (EL.U/mL) in the sera of subjects seronegative before vaccination.
Number of Subjects With Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Equal to or Above (≥) 8	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C , 19F and 23F ≥ 8.
Number of Subjects With Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes 6A and 19A Equal to or Above (≥) 8	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Seroprotection status, defined as Anti-HBs antibody concentrations ≥ 10 mIU/mL
Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Seropositivity status, defined as Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 microgram per milliliter (µg/mL).
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 0.15 Microgram Per Milliliter (µg/ mL)	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Cut-off values assessed were greater than or equal to 0.15 microgram per milliliter (µg/ mL) in the sera of subjects.
Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Seroprotection status, defined as Anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL
Number of Subjects With Anti-diphtheria (Anti D) and Anti-tetanus Toxoids (Anti TT) Antibody Concentrations Equal to or Above 0.1 International Units Per Milliliter (IU/mL)	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Cut-off values assessed were greater than or equal to 0.1 International Units per milliliter (IU/mL) in the sera of subjects.
Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Seroprotection status, defined as Anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 IU/mL
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Within 4-day (Days 0-3) after each dose and across doses	Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Grade 3 (G3) drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 (G3) fever was defined as fever (rectal temperature) above (\>) 40.0 degree Celsius (°C). Grade 3 (G3) irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 (G3) loss of appetite was defined as the subject not eating at all. "Any" is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Related (REL) = Symptom assessed by the investigator as causally related to vaccination.
Number of Subjects With Unsolicited Adverse Events (AEs)	Within 31 days (Days 0-30) after each vaccination	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" is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.
Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations Equal to or Above (≥) 0.2 Microgram Per Milliliter (µg/mL)	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Cut-off values assessed were greater than or equal to 0.2 microgram per milliliter (µg/mL) in the sera of subjects.
Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations Equal to or Above (≥) 0.05 Microgram Per Liter (µg/mL)	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Cut-off values assessed were greater than or equal to 0.05 microgram per liter (µg/mL) in the sera of subjects.
Concentrations of Antibodies Against Protein D (Anti-PD)	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Seropositivity status, defined as Anti-PD antibody concentrations ≥ 100 ELISA units per milliliter ( EL.U/mL)
Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above 10 Milli-International Units Per Milliliter (mIU/mL)	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Cut-off values assessed were greater than or equal to 10 milli-International Units per milliliter (mIU/mL) in the sera of subjects.
Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Titers Equal to or Above (≥) 8	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Titers were expressed as geometric mean titres (GMTs).
Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Seroprotection status, defined as Anti-polio type 1, Anti-polio type 2 and Anti-polio type 3 antibody titers ≥ 8
Number of Subjects With Serious Adverse Events (SAEs)	During the Active Phase: From Month 0 to Month 3 for Synflorix 1 Group and Prevenar 1 Group and from Month 0 to Month 5 for the Synflorix 2 Group and Prevenar 2 Group	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.
Number of Subjects With Serious Adverse (SAEs)	During the Extended Safety Follow-Up Phase: At Month 8 for Synflorix 1 Group and Prevenar 1 Group and at Month 10 for the Synflorix 2 Group and Prevenar 2 Group	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.
Concentrations of Antibodies Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	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).
Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Equal to or Above (≥) 0.05 Microgram Per Milliliter (μg/mL)	One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™	Cut-off values assessed were greater than or equal to 0.05 microgram per milliliter (μg/mL) in the sera of subjects seronegative before vaccination.
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL)	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Cut-off values assessed were greater than or equal to 1.0 microgram per milliliter (µg/mL) in the sera of subjects.
Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Seropositivity status, defined as Anti-BPT antibody concentrations ≥ 15 EL.U/mL.
Number of Subjects With Vaccine Response to Bordetella Pertussis	One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™	Vaccine response to B. pertussis;defined as appearance of antibodies in subjects initially seronegative (S-) (i.e., concentrations \< 15 EL.U/mL) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (S+) (i.e., with concentrations ≥ 15 EL.U/mL).

Trial Locations

Locations (1)

GSK Investigational Site; 🇵🇱 Wroclaw, Poland