Study to Evaluate GSK Biologicals' GSK2197870A Vaccine Given as Primary Course in Infants

Study Overview
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Brief Summary
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The purpose of this Phase II study is to evaluate the feasibility of GSK Biologicals' GSK2197870A vaccine co-administered with Wyeth-Lederle's Prevenar™ when given in healthy infants as a three-dose primary vaccination course at 2, 3 and 4 months of age followed by a booster dose of GSK Biologicals' Menitorix™ at 12 months of age.

Detailed Description
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This protocol posting has been updated following Protocol amendment 1, 11-February-2010; The Study design section is impacted by this amendment.

Official Title
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Study in Healthy Children of GSK Biologicals' DTPa-IPV/Hib-MenC-TT Vaccine, GSK2197870A, Co-administered With Prevenar™ as a Three-dose Primary Vaccination Course in Infancy Followed by a Booster Dose of Menitorix™ at 12 Months of Age

Conditions
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Neisseria Meningitidis, Haemophilus Influenzae Type b

Intervention / Treatment
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* Biological: GSK2197870A
* Biological: Prevenar™
* Biological: Menitorix™
* Biological: Pediacel™
* Biological: Menjugate™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must satisfy the following criteria at study entry: A male or female infant between, and including, 6 and 12 weeks of age at the time of the first vaccination. Born after 36 to 42 weeks of gestation. Subjects who the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol should be enrolled in the study. Written informed consent obtained from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study: Use of any investigational or non-registered product 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 of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period. 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 . Evidence of previous or intercurrent diphtheria, tetanus, pertussis, poliomyelitis, Hib, pneumococcal and/or group C meningococcal vaccination or disease. History of seizures or progressive neurological disease (one episode of febrile convulsion does not constitute an exclusion criterion). Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness. The following condition is temporary or self limiting and a subject may be vaccinated once the condition has resolved and no other exclusion criteria are met: • Current febrile illness or axillary temperature ≥37.5ºC or other moderate to severe illness within 24 hours of study vaccine administration

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2197870A Group<br>Subjects aged between and including 6 and 12 weeks of age at the time of first vaccination received 3 doses of GSK2197870A vaccine at Months 0, 1 and 2, 2 doses of Prevenar™ vaccine at Months 0 and 2 and a booster dose of Menitorix™ vaccine at Month 10. All vaccines were administered intramuscularly. GSK2197870A and Menitorix™ vaccines were administered in the right upper anterolateral thigh and Prevenar™ vaccine in the left upper anterolateral thigh. | Biological: GSK2197870A<br>* 3 doses given at 2, 3 and 4 months of age<br>* Other names: HiB and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine.;Biological: Prevenar™<br>* 3 co-administered doses, intramuscular into right thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;Biological: Menitorix™<br>* 1 booster dose at 12 months of age<br>* Other names: GSK Biologicals' combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine.;|
| Active Comparator: Pediacel Group<br>Subjects aged between and including 6 and 12 weeks of age at the time of first vaccination received 3 doses of Pediacel™ vaccine at Months 0, 1 and 2, 2 doses of Prevenar™ vaccine at Months 0 and 2, 2 doses of Menjugate™ vaccine at Months 1 and 2 and a booster dose of Menitorix™ at Month 10. All vaccines were administered intramuscularly. Pediacel™ and Menitorix™ vaccines were administered in the right upper anterolateral thigh and Prevenar™ vaccine in the left upper anterolateral thigh and Menjugate™ vaccine in the left lower anterolateral thigh. | Biological: Prevenar™<br>* 3 co-administered doses, intramuscular into right thigh<br>* Other names: Pfizer's 13-valent pneumococcal polysaccharide conjugate vaccine;Biological: Menitorix™<br>* 1 booster dose at 12 months of age<br>* Other names: GSK Biologicals' combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine.;Biological: Pediacel™<br>* 3 doses given at 2, 3 and 4 months of age<br>* Other names: Sanofi-Pasteur-MSD's combined DTPa-inactivated polio-Haemophilus influenzae type b vaccine.;Biological: Menjugate™<br>* 2 doses given at 3 and 4 months of age<br>* Other names: Novartis' meningococcal serogroup C CRM197 protein conjugated vaccine.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-polyribosylribitol Phosphate (Anti-PRP). | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | At Month 3 | 
| Number of Seropositive Subjects Against Neisseria Meningitidis Using Baby Rabbit Complement (rSBA-MenC) | A seropositive subject was defined as a vaccinated subject who had rSBA-MenC ≥ 1:8. | At Month 2 and Month 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-PRP Concentrations Antibody Above the Cut-off. | The reference cut-off was ≥ 1.0 micrograms per milliliter (µg/mL). | At Month 3 | 
| Number of Subjects With Anti-polysaccharide C (Anti-PSC ) Antibody Concentrations Above the Cut-offs. | The reference cut-offs were ≥ 0.3 µg/mL and ≥ 2 µg/mL. | At Month 2 and Month 3. | 
| Number of Seroprotected Subjects for Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. | A seroprotected subject was defined as a vaccinated subject who had anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | At Month 3. | 
| Number of Seropositive Subjects Against Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN). | A seropositive subject was defined as a vaccinated subject who had anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL). | At Month 3. | 
| Number of Seroprotected Subjects for Anti-poliovirus (Anti-polio) Types 1, 2 and 3. | A seroprotected subject was defined as a vaccinated subject who had anti-polio 1, 2 and 3 antibody concentrations ≥ 1:8. | At Month 3. | 
| Number of Seropositive Subjects for Anti-pneumococcal (Anti-PNE) Serotypes. | A seropositive subject was defined as a vaccinated subject who had anti- pneumococcal antibody concentrations ≥ 0.2 micrograms per milliliter (µg/mL). The anti-PNE serotypes assessed were 4, 6B, 9V, 14, 18C, 19F and 23F. | At Month 3 | 
| Concentrations for Anti-PRP. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.15 µg/mL. | At Month 3. | 
| Titers for rSBA-MenC. | Titers were expressed as geometric mean titers (GMCs). The seropositivity reference cut-off value was ≥ 1:8. | At Month 2 and Month 3. | 
| Concentrations for Anti-PSC. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.3 µg/mL. | At Month 2 and Month 3. | 
| Concentrations for Anti-T and Anti-D. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.1 IU/mL. | At Month 3. | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN. | Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity reference cut-off value was ≥ 5 EL.U/mL. | At Month 3. | 
| Titers for Anti-polio 1, 2 and 3. | Titers were expressed as geometric mean titers (GMTs). The seropositivity reference cut-off value was ≥ 1:8. | At Month 3. | 
| Concentrations for Anti-PNE Serotypes. | Concentrations were expressed as geometric mean concentreations (GMCs). The seropositivity reference cut-off value was ≥ 0.2 µg/mL. | At Month 3. | 
| Number of Seroprotected Subjects for Anti-PRP. | A seroprotected subject was defined as a vaccinated subject who had anti-PRP antibody concentrations ≥ 0.15 micrograms per milliliter (µg/mL). | At Month 10 and Month 11. | 
| Number of Seropositive Subjects Against rSBA-MenC. | A seropositive subject was defined as a vaccinated subject who had rSBA-MenC ≥ 1:8. | At Month 10 and Month 11. | 
| Number of Subjects With Anti-PSC Antibody Concentrations Above the Cut-offs. | The reference cut-offs were ≥ 0.3 µg/mL and ≥ 2 µg/mL. | At Month 10 and Month 11. | 
| Number of Seroprotive Subjects for Anti-D and Anti-T Antibodies. | A seropositive subject was defined as a vaccinated subject who had anti-D (ELISA) and anti-T antibody concentrations ≥ 0.1 IU/mL. Seropositivity for anti-D was also defined with the ≥ 0.016 IU/mL cut-off (Neutralisation assay). | At Month 10. | 
| Number of Seropositive Subjects for Anti-PT, Anti-FHA and Anti-PRN. | A seropositive subject was defined as a vaccinated subject who had anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliters (EL.U/mL). | At Month 10. | 
| Number of Seroprotected Subjects for Anti-anti-polio Types 1, 2 and 3. | A seroprotected subject was defined as a vaccinated subject who had anti-polio 1, 2 and 3 antibody concentrations ≥ 1:8. | At Month 10. | 
| Concentrations for Anti-PRP. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.15 µg/mL. | At Month 10 and Month 11. | 
| Titers for rSBA-MenC. | Titers were expressed as geometric mean titers (GMCs). The seropositivity reference cut-off value was ≥ 1:8. | At Month 10 and Month 11. | 
| Concentrations for Anti-PSC. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.3 µg/mL. | At Month 10 and Month 11. | 
| Concentrations for Anti-T and Anti-D. | Concentrations were expressed as geometric mean concentrations (GMCs). The seroprotection reference cut-off value was ≥ 0.1 IU/mL. Seropositivity for anti-D was also defined with the ≥ 0.016 IU/mL cut-off (Neutralisation assay). | At Month 10. | 
| Concentrations for Anti-PT, Anti-FHA and Anti-PRN. | Concentrations were expressed as geometric mean concentrations (GMCs). The seropositivity reference cut-off value was ≥ 5 EL.U/mL. | At Month 10. | 
| Titers for Anti-polio 1, 2 and 3. | Titers were expressed as geometric mean titers (GMTs). The seroprotection reference cut-off value was ≥ 1:8. | At Month 10. | 
| Number of Subjects With a Booster Response to rSBA-MenC Antibodies. | Booster response defined as: for initially seronegative subjects, antibody titre ≥ 1:32 at post-booster (Month 11); for initially seropositive subjects, antibody titres at post-booster ≥ 4 fold the pre-booster. | At Month 11 | 
| Number of Subjects With a Booster Response to Anti-PRP Antibodies. | Booster response defined as: for initially seronegative subjects, antibody concentration ≥ 0.6 µg/mL at post-booster (Month 11); for initially seropositive subjects, antibody concentrations at post-booster ≥ 4 fold the pre-booster. | At Month 11 | 
| Number of Subjects With a Booster Response to Anti-PSC Antibodies. | Booster response defined as: for initially seronegative subjects, antibody concentration ≥ 1.2 µg/mL at post-booster (Month 11); for initially seropositive subjects, antibody concentrations at post-booster ≥ 4 fold the pre-booster. | At Month 11 | 
| Number of Subjects Reporting Any Solicited Local Symptoms. | Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. | During the 8-day (Days 0-7) | 
| Number of Subjects Reporting Any Solicited General Symptoms. | Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever [axillary temperature above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of any local symptom regardless of intensity grade. | During the 8-day (Days 0-7) | 
| Number of Subjects Reporting Any Unsolicited Adverse Events (AEs). | An unsolicited AE is any AE (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. Any = occurrence of an AE regardless of intensity grade or relationship to study vaccination. | Within the 31-day (Days 0-30) follow up period after vaccination. | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs). | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization or results in disability/incapacity of a study subjects. Any SAE = any SAE regardless of assessment of relationship to study vaccination. | During the entire study period (Month 0 to Month 11) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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combined, Vaccines