Primary & Booster Study to Evaluate the Immunogenicity and Safety of Menitorix Vaccine in Preterm Infants

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00586612
• Collaborator: (none)
• Enrollment: 313
• Locations: 8
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 39.1
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The purpose of this Phase IIIb study is to evaluate the immunogenicity, reactogenicity & safety of GSK Biologicals' Hib-MenC vaccine (Menitorix™) when co-administered with GSK Biologicals' DTPa-HBV-IPV vaccine (Infanrix™ penta) & Wyeth's 7-valent pneumococcal conjugate vaccine (Prevenar™) in preterm infants as a 3-dose primary vaccination course during the first 6 months of life (at 2, 4, 6 months of age) and of a booster dose of Menitorix™ when co-administered with GSK Biologicals' DTPa-IPV vaccine (Infanrix IPV) and Wyeth's Prevenar in the second year of life (16-18 months of age). The control is a group of full-term infants receiving the same vaccines. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or Disease	Intervention/Treatment	Phase
Haemophilus Influenzae Type b; Neisseria Meningitidis	Biological: Menitorix™; Biological: Infanrix™ penta; Biological: Prevenar™; Biological: Infanrix™ IPV	Phase 3

Detailed Description

This multicenter study is open & consists of a primary & a booster phase. The study has 2 treatment groups (Preterm & Full-term) that will receive the same vaccinations; the Full-term group will be the active control. Four blood samples will be collected from all subjects for immunogenicity analyses; 2 in the primary phase at prior to the first vaccination and one month after the third vaccination and 2 in the booster phase at prior to booster dose and one month after booster dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 313 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity & Safety Study in Preterm & Full-term Infants of GSK Biologicals' Hib-MenC Vaccine, Menitorix™ Co-administered With Infanrix™ Penta & Prevenar™ at 2, 4, 6 Months & as a Booster With Infanrix™ IPV & Prevenar™ at 16-18 Months
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Dec 30, 2008
• Actual Study Completion Date: Dec 30, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Preterm group Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Biological: Menitorix™; Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.; Biological: Infanrix™ penta; Intramuscular injection, 3 doses in the primary study; Biological: Prevenar™; Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.; Biological: Infanrix™ IPV; Intramuscular injection, 1 dose in the Booster study.
Active Comparator: Full-term group Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Biological: Menitorix™; Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.; Biological: Infanrix™ penta; Intramuscular injection, 3 doses in the primary study; Biological: Prevenar™; Intramuscular injection, 3 doses in the primary study and 1 dose in the Booster study.; Biological: Infanrix™ IPV; Intramuscular injection, 1 dose in the Booster study.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL) [One month after the third vaccination]

   Anti-PRP antibody concentration greater than or equal to 0.15 µg/mL is indicative of protection.

2. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to 1:8 [One month after the third vaccination]

   rSBA-MenC titer greater than or equal to 1:8 is indicative of protection.

Secondary Outcome Measures

1. Number of Subjects With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to the Cut-off Values [Before vaccination (at Day 0)]

   Anti-PRP antibody cut-off values assessed include 0.15 micrograms per milliliter (µg/mL) and 1 µg/mL.

2. Number of Subject With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1 Microgram Per Milliliter [One month after the third vaccination]

   Anti-PRP antibody cut-off value assessed include 1 microgram per milliliter (µg/mL).

3. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values [Before vaccination (at Day 0)]

   rSBA-MenC titer cut-off values assessed include 1:8, 1:32 and 1:128.

4. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values [One month after the third vaccination]

   rSBA-MenC titer cut-off values assessed include 1:32 and 1:128.

5. Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [Before vaccination (at Day 0)]

   Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2 µg/mL.

6. Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [One month after the third dose]

   Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2 µg/mL.

7. Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [Before vaccination (at Day 0)]

   Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.

8. Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values [One month after the third dose]

   Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.

9. Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration [Before vaccination (at Day 0)]

   Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) expressed micrograms per milliliter (µg/mL).

10. Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration [One month after the third dose]

    Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) expressed micrograms per milliliter (µg/mL).

11. Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration [Before vaccination (at Day 0)]

    Anti-HBs concentrations are given as geometric mean concentrations (GMCs) expressed in milli-international units per milliliter (mIU/mL).

12. Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration [One month after the third dose]

    Anti-HBs concentrations are given as geometric mean concentrations (GMCs) expressed in milli-international units per milliliter (mIU/mL).

13. Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer [Before vaccination (at Day 0)]

    rSBA-MenC titers are given as geometric mean titers (GMTs).

14. Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer [One month after the third dose]

    rSBA-MenC titers are given as geometric mean titers (GMTs).

15. Number of Subjects Reporting Solicited Local Symptoms [During the 4-day follow-up period after any primary vaccination dose]

    Solicited local symptoms assessed include pain, redness and swelling and are presented across doses.

16. Number of Subjects Reporting Solicited General Symptoms [During the 4-day follow-up period after any primary vaccination dose]

    Solicited general symptoms assessed include drowsiness, fever, irritability/fussiness and loss of appetite and are presented across doses.

17. Number of Subjects Reporting Unsolicited Adverse Events (AEs) [Within 31 days after each primary vaccination]

    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.

18. Number of Subjects Reporting Serious Adverse Events (SAEs) [Throughout the entire primary vaccination phase]

    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.

19. Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Migrogram Per Milliliter (µg/mL) [Prior to (Month 14) and one month after the booster vaccination (Month 15)]

    Anti-PRP antibody cut-off value assessed was 0.15 migrogram per milliliter (µg/mL).

20. Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1.0 Migrogram Per Milliliter (µg/mL) [Prior to (Month 14) and one month after the booster vaccination (Month 15)]

    Anti-PRP antibody cut-off value assessed was 1.0 migrogram per milliliter (µg/mL).

21. Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values [Prior to (Month 14) and one month after the booster vaccination (Month 15)]

    rSBA-MenC titer cut-off values assessed include 1:8, 1:32 and 1:128.

22. Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to the Cut-off Values [Prior to (Month 14) and one month after the booster vaccination (Month 15)]

    Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2.0 µg/mL.

23. Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to the Cut-off Values [Prior to (Month 14) the booster vaccination]

    Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL. Note: the protocol planned an analysis on HBs after the booster dose, but this analysis was not performed as the vaccines administered as booster doses did not contain HBs component.

24. Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration [Prior to (Month 14) and one month after the booster vaccination (Month 15)]

    Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) in micrograms per milliliter (µg/mL).

25. Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration [Prior to (Month 14) the booster vaccination]

    Anti-HBs concentrations are given as geometric mean concentrations (GMCs) in milli-international units per milliliter (mIU/mL). Note: Planned analysis in the protocol of HBs after the booster dose was not performed as booster vaccines did not contain HBs component.

26. Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer [Prior to (Month 14) and one month after the booster vaccination (Month 15)]

    rSBA-MenC titers are given as geometric mean titers (GMTs).

27. Number of Subjects Reporting Solicited Symptoms (Local and General) [During the 4-day follow-up period following booster vaccination]

    Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability/fussiness and loss of appetite.

28. Number of Subjects Reporting Unsolicited Adverse Events (AEs) [Within 31 days after the booster vaccination (month 15)]

    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.

29. Number of Subjects Reporting Serious Adverse Events (SAEs) [31 days after last primary vaccination until administration of booster dose (Month 14) and from the administration of the booster dose until the end of the study (Month 15)]

    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. Period 1 is defined as 31 days after last primary vaccination until administration of booster dose (Month 14). Period 2 is defined as the administration of the booster dose until the end of the study (Month 15).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Weeks to 12 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.

• A male or female between, and including, 8 and 12 weeks of age at the time of the first vaccination.

• Written informed consent obtained from the parent or guardian of the subject.

All preterm subjects must satisfy the following criteria at study entry:

• Born after a gestation period of less than or equal to 36 weeks (≤258 days).

• Medically stable, i.e. do not require significant medical support or ongoing management for debilitating disease and have demonstrated a clinical course of sustained recovery.

All full-term subjects must satisfy the following criteria at study entry:

• Born after a gestation period between and including 37 and 42 weeks (≥259 days and ≤294 days).

• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

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.

• Chronic administration of immunosuppressants or other immune-modifying drugs since birth.

• Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of vaccine until the last study visit, except measles-mumps-rubella (MMR) and varicella vaccines which may be given according to local immunisation practices and except rotavirus oral vaccine which is allowed at anytime during the study after hospital discharge as per prescribing information.

• Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, meningococcal serogroup C and or Streptococcus pneumoniae disease, with the exception of hepatitis B vaccine or BCG vaccine given in the first month of life according to the national recommendations (although BCG and hepatitis B vaccines should have been given outside a 30-day window from the first administration of study vaccines).

• History of diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.

• A family history of congenital or hereditary immunodeficiency.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).

• Major congenital defects or serious chronic illness.

• History of any neurologic disorders or seizures.

• Acute disease at the time of enrolment.

• Administration of immunoglobulins (with the exception of monoclonal antibodies against respiratory syncytial virus [RSV]) and/or any blood products within one month (30 days) preceding the first dose of study vaccines.

• Planned administration of immunoglobulins and/or any blood products during the active phase of the study.

Specific criteria for the booster part of the study (to be checked at Visit 5, study month 14):

• History of diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.

• Previous vaccination, except the study vaccines and hepatitis birth dose, against diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and or S. pneumoniae disease.

• Previous booster vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, H. influenzae type b, meningococcal disease and/or S. pneumoniae disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Barcelona		Spain	08035
2	GSK Investigational Site	Bilbao		Spain	48013
3	GSK Investigational Site	Burgos		Spain	09005
4	GSK Investigational Site	Getafe		Spain	28905
5	GSK Investigational Site	Madrid		Spain	28041
6	GSK Investigational Site	Madrid		Spain	28047
7	GSK Investigational Site	Malaga		Spain	29010
8	GSK Investigational Site	Móstoles/Madrid		Spain	28935

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

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00586612
• Other Study ID Numbers: 110215; 110217
• First Posted: Jan 4, 2008
• Last Update Posted: Aug 27, 2018
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Conjugate vaccine; Persistence; Hib vaccine; Combination vaccine; Meningococcal vaccine; Safety; Preterm/full-term infants; Immunogenicity
• Additional relevant MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Period Title: Primary Phase
STARTED	163	150
COMPLETED	162	147
NOT COMPLETED	1	3
Period Title: Primary Phase
STARTED	154	144
COMPLETED	151	143
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Preterm Group	Full-term Group	Total
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Total of all reporting groups
Overall Participants	163	150	313
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	8.9 (1.15)	8.8 (0.79)	8.9 (0.99)
Sex: Female, Male (Count of Participants)
Female	77 47.2%	65 43.3%	142 45.4%
Male	86 52.8%	85 56.7%	171 54.6%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL)
Description	Anti-PRP antibody concentration greater than or equal to 0.15 µg/mL is indicative of protection.
Time Frame	One month after the third vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	140	142
Number [subjects]	139	141

2. Primary Outcome

Title	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to 1:8
Description	rSBA-MenC titer greater than or equal to 1:8 is indicative of protection.
Time Frame	One month after the third vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	143	140
Number [subjects]	142	140

3. Secondary Outcome

Title	Number of Subjects With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to the Cut-off Values
Description	Anti-PRP antibody cut-off values assessed include 0.15 micrograms per milliliter (µg/mL) and 1 µg/mL.
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	140	138
≥ 0.15 µg/mL	38	43
≥ 1.0 µg/mL	5	9

4. Secondary Outcome

Title	Number of Subject With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1 Microgram Per Milliliter
Description	Anti-PRP antibody cut-off value assessed include 1 microgram per milliliter (µg/mL).
Time Frame	One month after the third vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	140	142
Number [subjects]	133	134

5. Secondary Outcome

Title	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values
Description	rSBA-MenC titer cut-off values assessed include 1:8, 1:32 and 1:128.
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	141	137
≥ 1:8	16	23
≥ 1:32	5	11
≥ 1:128	0	3

6. Secondary Outcome

Title	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values
Description	rSBA-MenC titer cut-off values assessed include 1:32 and 1:128.
Time Frame	One month after the third vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	143	140
≥ 1:32	142	139
≥ 1:128	135	136

7. Secondary Outcome

Title	Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
Description	Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2 µg/mL.
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	142	137
≥ 0.3 µg/mL	23	36
≥ 2.0 µg/mL	3	8

8. Secondary Outcome

Title	Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
Description	Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2 µg/mL.
Time Frame	One month after the third dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	140	141
≥ 0.3 µg/mL	140	141
≥ 2.0 µg/mL	127	136

9. Secondary Outcome

Title	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
Description	Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	112	118
≥ 10 mIU/mL	89	78
≥ 100 mIU/mL	3	8

10. Secondary Outcome

Title	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to (≥) the Cut-off Values
Description	Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL.
Time Frame	One month after the third dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	129	129
≥ 10 mIU/mL	128	129
≥ 100 mIU/mL	109	117

11. Secondary Outcome

Title	Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration
Description	Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) expressed micrograms per milliliter (µg/mL).
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	142	138
Anti-PRP (n=140, 138)	0.116	0.140
Anti-PSC (n=142, 137)	0.19	0.25

12. Secondary Outcome

Title	Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration
Description	Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) expressed micrograms per milliliter (µg/mL).
Time Frame	One month after the third dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	140	142
Anti-PRP (n= 140, 142)	10.437	10.473
Anti-PSC (n= 140, 141)	6.34	7.46

13. Secondary Outcome

Title	Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration
Description	Anti-HBs concentrations are given as geometric mean concentrations (GMCs) expressed in milli-international units per milliliter (mIU/mL).
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	112	118
Geometric Mean (95% Confidence Interval) [mIU/mL]	24.79	16.67

14. Secondary Outcome

Title	Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration
Description	Anti-HBs concentrations are given as geometric mean concentrations (GMCs) expressed in milli-international units per milliliter (mIU/mL).
Time Frame	One month after the third dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	129	129
Geometric Mean (95% Confidence Interval) [mIU/mL]	372.30	586.58

15. Secondary Outcome

Title	Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer
Description	rSBA-MenC titers are given as geometric mean titers (GMTs).
Time Frame	Before vaccination (at Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	141	137
Geometric Mean (95% Confidence Interval) [Titer]	4.9	5.9

16. Secondary Outcome

Title	Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer
Description	rSBA-MenC titers are given as geometric mean titers (GMTs).
Time Frame	One month after the third dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary According-To-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	143	140
Geometric Mean (95% Confidence Interval) [Titer]	1055.9	1346.2

17. Secondary Outcome

Title	Number of Subjects Reporting Solicited Local Symptoms
Description	Solicited local symptoms assessed include pain, redness and swelling and are presented across doses.
Time Frame	During the 4-day follow-up period after any primary vaccination dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary Total Vaccinated Cohort.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	163	150
Pain	106	100
Redness	94	123
Swelling	91	113

18. Secondary Outcome

Title	Number of Subjects Reporting Solicited General Symptoms
Description	Solicited general symptoms assessed include drowsiness, fever, irritability/fussiness and loss of appetite and are presented across doses.
Time Frame	During the 4-day follow-up period after any primary vaccination dose

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary Total Vaccinated Cohort.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	163	150
Drowsiness	111	102
Fever	89	85
Irritability/fussiness	128	105
Loss of appetite	99	100

19. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (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 each primary vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary Total Vaccinated Cohort.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	163	150
Number [subjects]	56	72

20. Secondary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Description	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.
Time Frame	Throughout the entire primary vaccination phase

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Primary Total Vaccinated Cohort.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	163	150
Number [subjects]	11	8

21. Secondary Outcome

Title	Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Migrogram Per Milliliter (µg/mL)
Description	Anti-PRP antibody cut-off value assessed was 0.15 migrogram per milliliter (µg/mL).
Time Frame	Prior to (Month 14) and one month after the booster vaccination (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	133	134
Pre-booster (n= 133; 130)	116	117
Post-booster (n= 132; 134)	132	134

22. Secondary Outcome

Title	Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 1.0 Migrogram Per Milliliter (µg/mL)
Description	Anti-PRP antibody cut-off value assessed was 1.0 migrogram per milliliter (µg/mL).
Time Frame	Prior to (Month 14) and one month after the booster vaccination (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	133	134
Pre-booster (n= 133; 130)	53	53
Post-booster (n= 132; 134)	132	134

23. Secondary Outcome

Title	Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to the Cut-off Values
Description	rSBA-MenC titer cut-off values assessed include 1:8, 1:32 and 1:128.
Time Frame	Prior to (Month 14) and one month after the booster vaccination (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	134	137
≥ 1:8 pre-booster (n= 134; 134)	102	117
≥ 1:8 post-booster (n= 133; 137)	132	136
≥ 1:32 pre-booster (n= 134; 134)	95	115
≥ 1:32 post-booster (n= 133; 137)	132	136
≥ 1:128 pre-booster (n= 134; 134)	69	85
≥ 1:128 post-booster (n= 133; 137)	131	136

24. Secondary Outcome

Title	Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to the Cut-off Values
Description	Anti-PSC antibody cut-off values assessed include 0.3 micrograms per milliliter (µg/mL) and 2.0 µg/mL.
Time Frame	Prior to (Month 14) and one month after the booster vaccination (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	130	129
≥ 0.3 µg/mL pre-booster (n= 130; 127)	74	92
≥ 0.3 µg/mL post-booster (n= 117; 129)	116	129
≥ 2.0 µg/mL pre-booster (n= 130; 127)	11	11
≥ 2.0 µg/mL post-booster (n= 117; 129)	105	124

25. Secondary Outcome

Title	Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentration Greater Than or Equal to the Cut-off Values
Description	Anti-HBs antibody cut-off values assessed include 10 milli-international units per milliliter (mIU/mL) and 100 mIU/mL. Note: the protocol planned an analysis on HBs after the booster dose, but this analysis was not performed as the vaccines administered as booster doses did not contain HBs component.
Time Frame	Prior to (Month 14) the booster vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	125	116
≥ 10 mIU/mL pre-booster	121	113
≥ 100 mIU/mL pre-booster	61	71

26. Secondary Outcome

Title	Anti-polyribosylribitol Phosphate (Anti-PRP) and Anti-polysaccharide C (Anti-PSC) Concentration
Description	Anti-PRP and anti-PSC concentrations are given as geometric mean concentrations (GMCs) in micrograms per milliliter (µg/mL).
Time Frame	Prior to (Month 14) and one month after the booster vaccination (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	133	134
anti-PRP pre-booster (n= 133; 130)	0.706	0.777
anti-PRP post-booster (n= 132; 134)	50.343	54.625
anti-PSC pre-booster (n= 130; 127)	0.42	0.56
anti-PSC post-booster (n= 117; 129)	10.06	11.31

27. Secondary Outcome

Title	Anti-hepatitis B Surface Antigen (Anti-HBs) Concentration
Description	Anti-HBs concentrations are given as geometric mean concentrations (GMCs) in milli-international units per milliliter (mIU/mL). Note: Planned analysis in the protocol of HBs after the booster dose was not performed as booster vaccines did not contain HBs component.
Time Frame	Prior to (Month 14) the booster vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	125	116
Geometric Mean (95% Confidence Interval) [mIU/mL]	95.9	145.6

28. Secondary Outcome

Title	Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titer
Description	rSBA-MenC titers are given as geometric mean titers (GMTs).
Time Frame	Prior to (Month 14) and one month after the booster vaccination (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster ATP cohort for immunogenicity, which included subjects having received 3 vaccine doses during the primary vaccination course and the booster vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component after booster dose administration.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	134	137
Pre-booster (n= 134; 134)	79.3	147.8
Post-booster (n= 133; 137)	4883.1	5288.8

29. Secondary Outcome

Title	Number of Subjects Reporting Solicited Symptoms (Local and General)
Description	Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability/fussiness and loss of appetite.
Time Frame	During the 4-day follow-up period following booster vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster Total Vaccinated cohort which included all vaccinated subjects for whom data for the booster phase were available.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	154	144
Pain	82	98
Redness	77	109
Swelling	67	94
Drowsiness	33	46
Fever	43	53
Irritability	70	69
Loss of appetite	34	50

30. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (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 the booster vaccination (month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster Total Vaccinated cohort which included all vaccinated subjects for whom data for the booster phase were available.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	154	144
Number [subjects]	34	42

31. Secondary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Description	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. Period 1 is defined as 31 days after last primary vaccination until administration of booster dose (Month 14). Period 2 is defined as the administration of the booster dose until the end of the study (Month 15).
Time Frame	31 days after last primary vaccination until administration of booster dose (Month 14) and from the administration of the booster dose until the end of the study (Month 15)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Booster Total Vaccinated cohort which included all vaccinated subjects for whom data for the booster phase were available.

Arm/Group Title	Preterm Group	Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.	Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
Measure Participants	154	144
Period 1	10	2
Period 2	1	0

Adverse Events

Time Frame	For SAEs: the whole study period (Day 0 - Month 15); For frequent adverse events: solicited adverse events a 4-day period after vaccination, unsolicited adverse events a 31-day period after vaccination.
Adverse Event Reporting Description	Solicited adverse events after primary and booster vaccination are put as separate adverse events. In the description field of these adverse events it is specified to which vaccination phase they belong.
Arm/Group Title	Preterm Group		Full-term Group
Arm/Group Description	Subjects born after a gestation period of less than or equal to 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.		Subjects born after a gestation period of more than 36 weeks and who received 3 doses (at 2, 4 and 6 months of age) of Menitorix™, Infanrix™ penta and Prevenar™ and a booster dose of Menitorix™, Infanrix™ IPV and Prevenar™ at 16-18 months of age.
All Cause Mortality
	Preterm Group		Full-term Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Preterm Group		Full-term Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/163 (13.5%)		10/150 (6.7%)
Eye disorders
Conjunctivitis	1/163 (0.6%)		0/150 (0%)
Infections and infestations
Bronchiolitis	6/163 (3.7%)		2/150 (1.3%)
Pneumonia	4/163 (2.5%)		1/150 (0.7%)
Respiratory syncytial virus bronchiolitis	1/163 (0.6%)		1/150 (0.7%)
Upper respiratory tract infection	3/163 (1.8%)		0/150 (0%)
Candidiasis	1/163 (0.6%)		0/150 (0%)
Escherichia urinary tract infection	1/163 (0.6%)		0/150 (0%)
Gastroenteritis	1/163 (0.6%)		1/150 (0.7%)
Lower respiratory tract infection	1/163 (0.6%)		1/150 (0.7%)
Meningococcal sepsis	0/163 (0%)		1/150 (0.7%)
Osteomyelitis	0/163 (0%)		1/150 (0.7%)
Pyelonephritis acute	0/163 (0%)		1/150 (0.7%)
Streptococcal sepsis	1/163 (0.6%)		0/150 (0%)
Urinary tract infection	0/163 (0%)		1/150 (0.7%)
Cellulitis	1/163 (0.6%)		1/150 (0.7%)
Gastroenteritis rotavirus	0/163 (0%)		2/150 (1.3%)
Bronchitis	1/163 (0.6%)		0/150 (0%)
Bronchopneumonia	1/163 (0.6%)		0/150 (0%)
Otitis media acute	1/163 (0.6%)		0/150 (0%)
Respiratory tract infection	1/163 (0.6%)		0/150 (0%)
Arthritis bacterial	1/163 (0.6%)		0/150 (0%)
Metabolism and nutrition disorders
Malnutrition	1/163 (0.6%)		0/150 (0%)
Respiratory, thoracic and mediastinal disorders
Apnoea	1/163 (0.6%)		0/150 (0%)
Bronchospasm	4/163 (2.5%)		0/150 (0%)
Hypoxia	1/163 (0.6%)		0/150 (0%)
Other (Not Including Serious) Adverse Events
	Preterm Group		Full-term Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	153/163 (93.9%)		144/150 (96%)
Gastrointestinal disorders
Vomiting	9/163 (5.5%)		6/150 (4%)
General disorders
Injection site nodule	3/163 (1.8%)		24/150 (16%)
Injection site haematoma	1/163 (0.6%)		9/150 (6%)
Pain	106/163 (65%)		100/150 (66.7%)
Redness	94/163 (57.7%)		123/150 (82%)
Swelling	91/163 (55.8%)		113/150 (75.3%)
Drowsiness	111/163 (68.1%)		102/150 (68%)
Fever	89/163 (54.6%)		85/150 (56.7%)
Irritability/fussiness	128/163 (78.5%)		105/150 (70%)
Loss of appetite	99/163 (60.7%)		100/150 (66.7%)
Pain	82/154 (53.2%)		98/144 (68.1%)
Redness	77/154 (50%)		109/144 (75.7%)
Swelling	67/154 (43.5%)		94/144 (65.3%)
Drowsiness	33/154 (21.4%)		46/144 (31.9%)
Fever	43/154 (27.9%)		53/144 (36.8%)
Irritability/fussiness	70/154 (45.5%)		69/144 (47.9%)
Loss of appetite	34/154 (22.1%)		50/144 (34.7%)
Infections and infestations
Upper respiratory tract infection	7/163 (4.3%)		11/150 (7.3%)

Limitations/Caveats

[Not Specified]

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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.