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

Study Overview
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Brief Summary
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The purpose of the present study is to demonstrate that the changes in the manufacturing process for the commercial lot of the pneumococcal conjugate vaccine GSK1024850A have no clinical impact and that the immune responses are non-inferior to the immune responses induced by the clinical lot. The study will be conducted in Singapore and Malaysia.

Official Title
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Non-inferiority of a Commercial Lot of the Pneumococcal Vaccine GSK1024850A Compared to a Clinical Lot.

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)
* Biological: Infanrix hexa
* Biological: Infanrix-IPV/Hib
* 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 parent(s)/guardian(s) can and will comply with the requirements of the protocol. Written or oral, signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child/ward. Free of any known or suspected 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. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of the study vaccines, or planned use during the study period. Concurrently participating in another clinical study, at any time during the study period. 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 (with the exception of hepatitis B immunoglobulins at birth). Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae (with the exception of vaccines where the first dose can be given within the first two weeks of life). Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of vaccine and ending 7 days after Dose 1 and Dose 2 and 30 days after Dose 3. History of, or intercurrent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, H. influenzae type b and rotavirus disease. 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. Gastroenteritis within 7 days preceding the study vaccine administration. Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix Clinical Lot & Infanrix Group<br>Subjects received 3 doses of the clinical lot of Synflorix TM (GSK1024850A) intramuscularly in the right thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 and 5 months of age in Malaysia or 2 and 5 months of age in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1). | Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)<br>* Intramuscular injection, 3 doses<br>Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore<br>* Other names: DTPa-combined vaccine;Biological: Infanrix-IPV/Hib<br>* Intramuscular injection, only for Visit 2 in Singapore<br>* Other names: DTPa-combined vaccine;Biological: Rotarix<br>* Oral, 2 doses<br>* Other names: HRV vaccine;|
| Experimental: Synflorix Commercial Lot Infanrix Group<br>Subjects received 3 doses of the commercial lot of Synflorix TM (GSK1024850A) intramuscularly in the lright thigh at 2-3-5 months of age (= study month 0, 1, 3) co-administered with a DTPa-combined vaccine (Infanrix hexa TM (at 2, 3 or 5 months of age in Malaysia or 2 and 5 months in Singapore) or Infanrix-IPV/Hib TM (at 3 months of age in Singapore)) intramuscularly in the left thigh and Rotarix TM orally at 2-3 months of age (= study month 0, 1). | Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)<br>* Intramuscular injection, 3 doses<br>Biological: Infanrix hexa<br>* Intramuscular injection, 3 doses in Malaysia and 2 doses in Singapore<br>* Other names: DTPa-combined vaccine;Biological: Infanrix-IPV/Hib<br>* Intramuscular injection, only for Visit 2 in Singapore<br>* Other names: DTPa-combined vaccine;Biological: Rotarix<br>* Oral, 2 doses<br>* Other names: HRV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine | Concentrations are given as Geometric Mean Concentrations (GMCs) in microgram per milliliter (μg/mL). Vaccine pneumococcal serotypes assessed included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | One month after primary immunization (month 4) | 
| Concentration of Antibody Against Protein D (PD) | Concentration was expressed as GMC in GSK's 22F enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | One month after primary immunization (month 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | One month after primary immunization (month 4) | 
| Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL | Anti-pneumococcal cross-reactive serotypes were 6A and 19A. | One month after primary immunization (month 4) | 
| Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8. | One month after primary immunization (month 4) | 
| Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes | Cross-reactive pneumococcal serotypes were 6A and 19A. Opsonophagocytic activity was defined as the dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cut-off of the assay was an opsonic titer equal to or greater than 8. | One month after primary immunization (month 4) | 
| Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes | Opsonophagocytic titers were expressed as GMTs. Cross-reactive pneumococcal serotypes included 6A and 19A. | One month after primary immunization (month 4) | 
| Poliovirus Types 1, 2 and 3 Titers | Titers were given as Geometric Mean Titers (GMTs). | One month after primary immunization (month 4) | 
| Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT) | Concentrations were defined as GMCs in international units per milliter (IU/mL) | One month after primary immunization (month 4) | 
| Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA). | Concentration was given as GMC in milli international units per milliliter (mIU/mL). As a decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL), the table shows results following partial or complete reanalysis. | One month after primary immunization (month 4) | 
| Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA) | Concentration was expressed as GMC in units per milliliter (U/mL). | 3 months after primary immunization (month 4) | 
| Occurrence of Serious Adverse Events | SAEs assessed include medical occurrences that result in death, is 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. | Following vaccination and throughout the entire study period (Month 0 to Month 4) | 
| Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes | Titers are presented as Geometric Mean Titers (GMTs). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. | One month after primary immunization (month 4) | 
| Number of Subjects With Solicited Local and General Symptoms. | Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were drowsiness, fever, irritability, loss of appetite, diarrhoea and vomiting. | Within 4 days (day 0-3) after vaccination | 
| Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) | Concentrations are expressed as GMCs in EL.U/mL. | One month after primary immunization (month 4) | 
| Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP) | Concentrain was expressed as GMC in µg/mL. | One month after primary immunization (month 4) | 
| Occurrence of Unsolicited Adverse Events | 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. | Within 31 days (day 0-30) after vaccination | 

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