Clinical trial NCT00344318: Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' 10-valent Pneumococcal Conjugate Vaccine
Official title: To Assess the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Pneumococcal Conjugate Vaccine Compared to Prevenar™, Co-administered With DTPw-HBV/Hib & OPV or IPV Vaccines as a 3-dose Primary Immunization Course During the First 6 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Streptococcal
Keywords: Immunogenicity
Safety
Pneumococcal vaccine
Pneumococcal disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-06-26
Enrollment: 806
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Number of Subjects Reporting Rectal Temperature Above (>) 39.0 Degrees Celsius (°C)
timeFrame: Within 4 day (Days 0-3) after each dose and across doses
Secondary outcomes:
measure: Number of Subjects With Any and Any Grade 3 Solicited Local Symptoms
timeFrame: Within 4 day (Days 0-3) after each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within 4-day (Days 0-3) after each dose and across doses
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: Within 31 days (Days 0-30) after each vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: 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
measure: Number of Subjects With Serious Adverse (SAEs)
timeFrame: 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
measure: Concentrations of Antibodies Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: 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)
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: 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)
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: 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
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: 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)
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes 6A and 19A
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Number of Subjects With Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes 6A and 19A Equal to or Above (≥) 8
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Concentrations of Antibodies Against Protein D (Anti-PD)
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Number of Subjects With Concentrations of Antibodies Against Protein D (Anti-PD) Equal to or Above (≥) 100 ELISA Units Per Milliliter (EL.U/mL)
timeFrame: One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™
measure: Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 0.15 Microgram Per Milliliter (µg/ mL)
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL)
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: 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)
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above 10 Milli-International Units Per Milliliter (mIU/mL)
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Titers Equal to or Above (≥) 8
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: 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)
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
measure: Number of Subjects With Vaccine Response to Bordetella Pertussis
timeFrame: One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™
Other outcomes:
Locations:
city: Muntinlupa
country: Philippines
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Trzebnica
country: Poland
facility: GSK Investigational Site
city: Tuchola
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Knuf M, Szenborn L, Moro M, Petit C, Bermal N, Bernard L, Dieussaert I, Schuerman L. Immunogenicity of routinely used childhood vaccines when coadministered with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Pediatr Infect Dis J. 2009 Apr;28(4 Suppl):S97-S108. doi: 10.1097/INF.0b013e318199f61b.
citation: Bermal N, Szenborn L, Chrobot A, Alberto E, Lommel P, Gatchalian S, Dieussaert I, Schuerman L. The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediatr Infect Dis J. 2009 Apr;28(4 Suppl):S89-96. doi: 10.1097/INF.0b013e318199f901.
citation: Chevallier B, Vesikari T, Brzostek J, Knuf M, Bermal N, Aristegui J, Borys D, Cleerbout J, Lommel P, Schuerman L. Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with routine childhood vaccines. Pediatr Infect Dis J. 2009 Apr;28(4 Suppl):S109-18. doi: 10.1097/INF.0b013e318199f62d.