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

Phase 3

Completed

Conditions: Infections, Streptococcal

Interventions: Biological: Pneumococcal conjugate vaccine GSK1024850A (different lots)
Biological: Infanrix hexa
Biological: Infanrix-IPV/Hib
Biological: Rotarix

Registration Number: NCT00808444

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 466

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Synflorix Commercial Lot Infanrix Group	Infanrix hexa	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).
Synflorix Clinical Lot & Infanrix Group	Infanrix hexa	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).
Synflorix Commercial Lot Infanrix Group	Infanrix-IPV/Hib	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).
Synflorix Clinical Lot & Infanrix Group	Infanrix-IPV/Hib	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).
Synflorix Clinical Lot & Infanrix Group	Rotarix	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).
Synflorix Clinical Lot & Infanrix Group	Pneumococcal conjugate vaccine GSK1024850A (different lots)	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).
Synflorix Commercial Lot Infanrix Group	Pneumococcal conjugate vaccine GSK1024850A (different lots)	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).
Synflorix Commercial Lot Infanrix Group	Rotarix	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).

Primary Outcome Measures

Name	Time	Method
Concentrations of Antibodies Against Vaccine Components of the Pneumococcal Vaccine	One month after primary immunization (month 4)	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.
Concentration of Antibody Against Protein D (PD)	One month after primary immunization (month 4)	Concentration was expressed as GMC in GSK's 22F enzyme-linked-immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 µg/mL	One month after primary immunization (month 4)	Vaccine pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Number of Subjects With Anti-pneumococcal Cross-reactive Serotype Concentrations Equal to or Above 0.20 µg/mL	One month after primary immunization (month 4)	Anti-pneumococcal cross-reactive serotypes were 6A and 19A.
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes	One month after primary immunization (month 4)	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.
Number of Subjects With Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes	One month after primary immunization (month 4)	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.
Opsonophagocytic Titers of Cross-reactive Pneumococcal Serotypes	One month after primary immunization (month 4)	Opsonophagocytic titers were expressed as GMTs. Cross-reactive pneumococcal serotypes included 6A and 19A.
Poliovirus Types 1, 2 and 3 Titers	One month after primary immunization (month 4)	Titers were given as Geometric Mean Titers (GMTs).
Concentrations of Antibodies Against Diphteria Toxoid (DT) and Tetanus Toxoid (TT)	One month after primary immunization (month 4)	Concentrations were defined as GMCs in international units per milliter (IU/mL)
Concentration of Antibody Against Hepatitis B Surface Antigen (HBs) by Enzyme Linked ImmunoSorbent Assay (ELISA).	One month after primary immunization (month 4)	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.
Concentration of Antibody Against Rotavirus Immunoglobulin A (IgA)	3 months after primary immunization (month 4)	Concentration was expressed as GMC in units per milliliter (U/mL).
Occurrence of Serious Adverse Events	Following vaccination and throughout the entire study period (Month 0 to Month 4)	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.
Opsonophagocytic Titers of Vaccine Pneumococcal Serotypes	One month after primary immunization (month 4)	Titers are presented as Geometric Mean Titers (GMTs). Pneumococcal serotypes included 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
Number of Subjects With Solicited Local and General Symptoms.	Within 4 days (day 0-3) after vaccination	Solicited local symptoms were pain, redness and swelling. Solicited general symptoms were drowsiness, fever, irritability, loss of appetite, diarrhoea and vomiting.
Concentrations of Antibodies Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN)	One month after primary immunization (month 4)	Concentrations are expressed as GMCs in EL.U/mL.
Concentration of Antibody Against Polyribosyl-ribitol Phosphate (PRP)	One month after primary immunization (month 4)	Concentrain was expressed as GMC in µg/mL.
Occurrence of Unsolicited Adverse Events	Within 31 days (day 0-30) after 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.