Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6 to 12wks of Age

Study Overview
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Brief Summary
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The purpose of this study is to assess the immunogenicity in terms of antibody response and the safety/reactogenicity in terms of solicited and unsolicited symptoms and serious adverse events following primary vaccination of Mexican infants with pneumococcal conjugate vaccine GSK 1024850A co-administered with a diphtheria, tetanus, acellular pertussis (DTPa)-combined vaccine (Infanrix hexa) and rotavirus vaccine (Rotarix) in children during the first 6 months of age.

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

Official Title
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Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Infanrix Hexa and Rotarix

Conditions
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Infections, Streptococcal, Streptococcus Pneumoniae Vaccines

Intervention / Treatment
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* Biological: Synflorix
* Biological: Infanrix hexa
* Biological: Rotarix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between and including 6-12 weeks 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 of 36 to 42 weeks inclusive. 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. Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting one month before each dose of vaccines and ending 7 days after dose 1 and dose 2 and one month after dose 3. 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. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. A family history of congenital or hereditary immunodeficiency. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, rotavirus and/or Streptococcus pneumoniae; with the exception of vaccines where the first dose may be given at birth within the first two weeks of life according to national recommendations (e.g. Hepatitis B and BCG). History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b disease. Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of the vaccination). Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal (GI) tract, intussusception (IS) or other medical condition determined to be serious by the investigator. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of any neurological disorders or seizures. Major congenital defects or serious chronic illness. Acute disease at the time of enrolment.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix Vaccine Group<br>Subjects receiving Synflorix vaccine co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 2-4-6 months of age, and co-administered with HRV (Rotarix) vaccine at 2-4 months of age. | Biological: Synflorix<br>* Intramuscular injection, 3 doses.<br>* Other names: Pneumococcal conjugate vaccine GSK1024850A.;Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses.<br>Biological: Rotarix<br>* Oral, 2 doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Concentrations Against Pneumococcal Vaccine Serotypes | Concentrations were expressed as geometric mean concentration (GMC). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Antibody Concentrations Against Protein D | Concentrations were given as geometric mean concentration (GMC) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opsonophagocytic Titer Against Pneumococcal Vaccine Serotypes | The results were presented as the geometric mean dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects With Anti-pneumococcal Vaccine Serotypes Antibody Concentrations Greater Than or Equal to 0.2 Microgram Per Milliliter | The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes | Antibody concentrations were expressed as Geometric Mean Concentrations against pneumococcal cross-reactive serotypes 6A and 19A. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Opsonophagocytic Titer Against Pneumococcal Cross-reactive Serotypes | The results were presented as the geometric mean dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cross-reactive pneumococcal serotypes assessed include 6A and 19A. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects Seropositive Against Vaccine Pneumococcal Serotypes | Seropositivity was defined as anti-pneumococcal antibody concentration greater than or equal to 0.05 microgram per milliliter. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects Seropositive for Opsonic Titer Against Vaccine Pneumococcal Serotypes | Seropositivity was defined as an opsonic titer greater than or equal to 8. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects Seropositive Against Cross-reactive Pneumococcal Serotypes | Seropositivity was defined as anti-pneumococcal antibody concentration greater than or equal to 0.05 microgram per milliliter. The cross-reactive pneumococcal serotypes assessed include 6A and 19A. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects Seropositive for Opsonic Titer Against Cross-reactive Pneumococcal Serotypes | Seropositivity was defined as anti-pneumococcal antibody opsonic titer greater than or equal to 8. The vaccine pneumococcal cross-reactive serotypes assessed include 6A and 19A. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects Seropositive for Anti-Protein D Antibodies | Seropositivity was defined as antibody concentration greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter. | One month after the administration of the 3rd vaccine dose i.e. Month 5 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) | Grade 3 redness and swelling was > 30 millimeter (mm) and grade 3 pain was subjects crying when limb was moved/spontaneously painful. Any was occurrence of any local symptom regardless of grade and whatever the number of injections. | Within 4 days following any vaccine dose | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs | Any fever was defined as axillary temperature ≥ 37.5 degree centigrade (°C), grade 3 fever was axillary temperature > 39.5°C. Grade 3 drowsiness, irritability, and loss of appetite was general symptom which prevented normal everyday activities. Grade 3 diarrhea was ≥ 6 looser than normal stools/day and Grade 3 vomiting was ≥ 3 episodes of vomiting/day. Related was solicited general symptom considered by the investigator to have a causal relationship to study vaccination. | Within 4 days following any vaccine dose | 
| Number of Subjects Reporting Any Unsolicited AEs | Unsolicited AE covers any AE 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 31 days after any vaccine dose | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | Up to Month 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary vaccination, Safety, Pneumococcal vaccine., Pneumococcal disease, Immunogenicity