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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00489554
• Collaborator: (none)
• Enrollment: 230
• Locations: 2
• Arm: 1
• Actual Duration (Months): 8.9
• Patients Per Site: 115
• Patients Per Site Per Month: 12.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infections, Streptococcal; Streptococcus Pneumoniae Vaccines	Biological: Synflorix; Biological: Infanrix hexa; Biological: Rotarix	Phase 3

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 230 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Infanrix Hexa and Rotarix
• Actual Study Start Date: Jul 3, 2007
• Actual Primary Completion Date: Mar 31, 2008
• Actual Study Completion Date: Mar 31, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Synflorix Vaccine Group 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; Intramuscular injection, 3 doses.; Other Names: Pneumococcal conjugate vaccine GSK1024850A. ; Biological: Infanrix hexa; Intramuscular injection, 3 doses.; Biological: Rotarix; Oral, 2 doses.

Outcome Measures

Primary Outcome Measures

1. Antibody Concentrations Against Pneumococcal Vaccine Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

2. Antibody Concentrations Against Protein D [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   Concentrations were given as geometric mean concentration (GMC) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter.

Secondary Outcome Measures

1. Opsonophagocytic Titer Against Pneumococcal Vaccine Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

2. Number of Subjects With Anti-pneumococcal Vaccine Serotypes Antibody Concentrations Greater Than or Equal to 0.2 Microgram Per Milliliter [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.

3. Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   Antibody concentrations were expressed as Geometric Mean Concentrations against pneumococcal cross-reactive serotypes 6A and 19A.

4. Opsonophagocytic Titer Against Pneumococcal Cross-reactive Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

5. Number of Subjects Seropositive Against Vaccine Pneumococcal Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

6. Number of Subjects Seropositive for Opsonic Titer Against Vaccine Pneumococcal Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

7. Number of Subjects Seropositive Against Cross-reactive Pneumococcal Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

8. Number of Subjects Seropositive for Opsonic Titer Against Cross-reactive Pneumococcal Serotypes [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   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.

9. Number of Subjects Seropositive for Anti-Protein D Antibodies [One month after the administration of the 3rd vaccine dose i.e. Month 5]

   Seropositivity was defined as antibody concentration greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter.

10. Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [Within 4 days following any vaccine dose]

    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.

11. Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs [Within 4 days following any vaccine dose]

    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.

12. Number of Subjects Reporting Any Unsolicited AEs [Within 31 days after any vaccine dose]

    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.

13. Number of Subjects Reporting Any Serious Adverse Events (SAEs) [Up to Month 5]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 12 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Mexico city		Mexico	14000
2	GSK Investigational Site	Mexico		Mexico	14000

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Ruiz-Palacios G et al. Immunogenicity, safety and reactogenicity of the new 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in Mexican infants. Abstract presented at the XIII Congreso Latinoamericano de Infectología Pediátrica (SLIPE). Guayaquil, Ecuador, 12-15 August 2009.
• Ruiz-Palacios GM, Guerrero ML, Hernández-Delgado L, Lavalle-Villalobos A, Casas-Muñoz A, Cervantes-Apolinar Y, Moreira M, Schuerman L. Immunogenicity, reactogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Mexican infants. Hum Vaccin. 2011 Nov;7(11):1137-45. doi: 10.4161/hv.7.11.17984. Epub 2011 Nov 1.
• Schuerman L et al. Population variability in antibody responses following pneumococcal conjugate vaccination: experience with the non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Schuerman L et al. Population variability of opsonophagocytic activity following 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate (PHiD-CV) vaccination more limited than antibody responses. Abstract presented at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD). Tel Aviv, Israel, 14-18 March 2010.
• Silfverdal SA, Coremans V, François N, Borys D, Cleerbout J. Safety profile of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Expert Rev Vaccines. 2017 Feb;16(2):109-121. doi: 10.1586/14760584.2016.1164044. Epub 2016 Sep 30. Review.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00489554
• Other Study ID Numbers: 109661; 2015-001510-10
• First Posted: Jun 21, 2007
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Primary vaccination; Safety; Pneumococcal vaccine.; Pneumococcal disease; Immunogenicity
• Additional relevant MeSH terms: Pneumonia, Pneumococcal; Streptococcal Infections; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Period Title: Overall Study
STARTED	230
COMPLETED	226
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Overall Participants	230
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	8.2 (1.63)
Sex: Female, Male (Count of Participants)
Female	123 53.5%
Male	107 46.5%

Outcome Measures

1. Primary Outcome

Title	Antibody Concentrations Against Pneumococcal Vaccine Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Anti-1 antibody (N=219)	2.13
Anti-4 antibody (N=218)	3.04
Anti-5 antibody (N=218)	3.24
Anti-6B antibody (N=218)	1.32
Anti-7F antibody (N=218)	3.72
Anti-9V antibody (N=218)	3.71
Anti-14 antibody (N=218)	5.27
Anti-18C antibody (N=219)	6.05
Anti-19F antibody (N=219)	5.49
Anti-23F antibody (N=218)	2.00

2. Primary Outcome

Title	Antibody Concentrations Against Protein D
Description	Concentrations were given as geometric mean concentration (GMC) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Geometric Mean (95% Confidence Interval) [ELISA units per milliliter]	2923.2

3. Secondary Outcome

Title	Opsonophagocytic Titer Against Pneumococcal Vaccine Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	97
Opsono-1 titer (N=97)	94.1
Opsono-4 titer (N=97)	670.8
Opsono-5 titer (N=94)	148.8
Opsono-6B titer (N=96)	345.4
Opsono-7F titer (N=96)	4435.4
Opsono-9V titer (N=96)	1186.1
Opsono-14 titer (N=94)	1168.3
Opsono-18C titer (N=94)	222.9
Opsono-19F titer (N=92)	589.2
Opsono-23F titer (N=95)	1876.3

4. Secondary Outcome

Title	Number of Subjects With Anti-pneumococcal Vaccine Serotypes Antibody Concentrations Greater Than or Equal to 0.2 Microgram Per Milliliter
Description	The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Anti-1 antibody (N=219)	219
Anti-4 antibody (N=218)	218
Anti-5 antibody (N=218)	218
Anti-6B antibody (N=218)	203
Anti-7F antibody (N=218)	218
Anti-9V antibody (N=218)	218
Anti-14 antibody (N=218)	216
Anti-18C antibody (N=219)	218
Anti-19F antibody (N=219)	217
Anti-23F antibody (N=218)	207

5. Secondary Outcome

Title	Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes
Description	Antibody concentrations were expressed as Geometric Mean Concentrations against pneumococcal cross-reactive serotypes 6A and 19A.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Anti-6A antibody	0.28
Anti-19A antibody	0.26

6. Secondary Outcome

Title	Opsonophagocytic Titer Against Pneumococcal Cross-reactive Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	91
Opsono-6A titer (N=91)	159.2
Opsono-19A titer (N=81)	11.6

7. Secondary Outcome

Title	Number of Subjects Seropositive Against Vaccine Pneumococcal Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Anti-1 antibody (N=219)	219
Anti-4 antibody (N=218)	218
Anti-5 antibody (N=218)	218
Anti-6B antibody (N=218)	212
Anti-7F antibody (N=218)	218
Anti-9V antibody (N=218)	218
Anti-14 antibody (N=218)	218
Anti-18C antibody (N=219)	218
Anti-19F antibody (N=219)	219
Anti-23F antibody (N=218)	212

8. Secondary Outcome

Title	Number of Subjects Seropositive for Opsonic Titer Against Vaccine Pneumococcal Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	97
Opsono-1 titer (N=97)	83
Opsono-4 titer (N=97)	93
Opsono-5 titer (N=94)	93
Opsono-6B titer (N=96)	76
Opsono-7F titer (N=96)	96
Opsono-9V titer (N=96)	96
Opsono-14 titer (N=94)	93
Opsono-18C titer (N=94)	91
Opsono-19F titer (N=92)	90
Opsono-23F titer (N=95)	90

9. Secondary Outcome

Title	Number of Subjects Seropositive Against Cross-reactive Pneumococcal Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Anti-6A antibody	203
Anti-19A antibody	198

10. Secondary Outcome

Title	Number of Subjects Seropositive for Opsonic Titer Against Cross-reactive Pneumococcal Serotypes
Description	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.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	91
Opsono-6A titer (N=91)	69
Opsono-19A titer (N=81)	19

11. Secondary Outcome

Title	Number of Subjects Seropositive for Anti-Protein D Antibodies
Description	Seropositivity was defined as antibody concentration greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter.
Time Frame	One month after the administration of the 3rd vaccine dose i.e. Month 5

Outcome Measure Data

Analysis Population Description

Analysis was performed on According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom immunogenicity data were available.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	219
Number [subjects]	219

12. Secondary Outcome

Title	Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)
Description	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.
Time Frame	Within 4 days following any vaccine dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	230
Any pain	196
Grade 3 pain	80
Any redness	91
Grade 3 redness	0
Any swelling	178
Grade 3 swelling	10

13. Secondary Outcome

Title	Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs
Description	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.
Time Frame	Within 4 days following any vaccine dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	230
Any diarrhea	55
Grade 3 diarrhea	5
Related diarrhea	55
Any drowsiness	156
Grade 3 drowsiness	7
Related drowsiness	153
Any fever	147
Grade 3 fever	0
Related fever	147
Any irritability	198
Grade 3 irritability	21
Related irritability	196
Any loss of appetite	113
Grade 3 loss of appetite	1
Related loss of appetite	111
Any vomiting	56
Grade 3 vomiting	7
Related vomiting	56

14. Secondary Outcome

Title	Number of Subjects Reporting Any Unsolicited AEs
Description	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.
Time Frame	Within 31 days after any vaccine dose

Outcome Measure Data

Analysis Population Description

The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	230
Number [subjects]	174

15. Secondary Outcome

Title	Number of Subjects Reporting Any Serious Adverse Events (SAEs)
Description	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.
Time Frame	Up to Month 5

Outcome Measure Data

Analysis Population Description

The analysis was performed on Total Vaccinated cohort which included all subjects with the vaccine administration documented.

Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
Measure Participants	230
Number [subjects]	15

Adverse Events

Time Frame	Serious adverse events were assessed up to month 5. Systematically assessed frequent adverse events (AEs) and non-systematically assessed frequent AEs were assessed during 4 day and 31 day post vaccination period respectively.
Arm/Group Title	Synflorix Vaccine Group
Arm/Group Description	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.
All Cause Mortality
	Synflorix Vaccine Group
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Synflorix Vaccine Group
	Affected / at Risk (%)	# Events
Total	15/230 (6.5%)
Eye disorders
Conjunctivitis	1/230 (0.4%)
Infections and infestations
Bronchopneumonia	6/230 (2.6%)
Bronchiolitis	4/230 (1.7%)
Gastroenteritis	2/230 (0.9%)
Nasopharyngitis	2/230 (0.9%)
Herpangina	1/230 (0.4%)
Laryngitis	1/230 (0.4%)
Pharyngitis	1/230 (0.4%)
Pneumonia viral	1/230 (0.4%)
Metabolism and nutrition disorders
Dehydration	2/230 (0.9%)
Nervous system disorders
Cerebral infarction	1/230 (0.4%)
Convulsion	1/230 (0.4%)
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity	1/230 (0.4%)
Other (Not Including Serious) Adverse Events
	Synflorix Vaccine Group
	Affected / at Risk (%)	# Events
Total	229/230 (99.6%)
General disorders
Pain	196/230 (85.2%)
Redness	91/230 (39.6%)
Swelling	178/230 (77.4%)
Diarrhea	55/230 (23.9%)
Drowsiness	156/230 (67.8%)
Fever	147/230 (63.9%)
Irritability	198/230 (86.1%)
Loss of appetite	113/230 (49.1%)
Vomiting	56/230 (24.3%)
Nasopharyngitis	123/230 (53.5%)
Pharyngitis	37/230 (16.1%)
Conjunctivitis	21/230 (9.1%)
Cough	17/230 (7.4%)
Gastroenteritis	16/230 (7%)
Diarrhea	14/230 (6.1%)
Laryngitis	13/230 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.