To demonstrate that DTPa-HBV-IPV/Hib-MenC-TT co-administered with 10Pn, is non-inferior to DTPa-HBV-IPV/Hib coadministered

The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: 112157 (DTPA-HBV-IPV=HIB-MENC-TT-002) Title: Immunogenicity and safety study of GlaxoSmithKline Biologicals GSK2202083A vaccine in healthy infants at 2, 3 and 4 months of age. GSK2202083A (DTPa-HBV-IPV/Hib-MenC-TT): GlaxoSmithKline (GSK) Biologicals combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, Haemophilus influenzae type b (Hib), meningococcal serogroup C (MenC) and tetanus toxoid conjugate vaccine Rationale: The purpose of this study was to evaluate the safety and immunogenicity of a combined DTPa-HBV-IPV/Hib- MenC-TT vaccine, when co-administered with Synflorix in healthy infants at 2, 3 and 4 months of age. This study also aimed at demonstrating non-inferiority of combined DTPa-HBV-IPV/Hib-MenC-TT vaccine, co-administered with Synflorix to Infanrix hexa co-administered with Menjugate or Synflorix. In accordance with the local recommended immunisation schedule, all subjects received 2 doses of Rotarix at 2 and 3 months of age. Infanrix hexa (DTPa-HBV-IPV/Hib): GSK Biologicals combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccine. Synflorix (10Pn): GSK Biologicals 10-valent pneumococcal-protein D, diphtheria and tetanus toxoid conjugate vaccine Menjugate (MenC-CRM): Novartis meningococcal serogroup C Cross Reacting Material 197 (CRM197) conjugated vaccine. Rotarix (HRV): GSK Biologicals live attenuated human rotavirus vaccine. Phase: II Study Period: 13 August 2009 to 27 January 2010. Study Design: Open, randomised (1:1:1), multicentre study with 3 parallel groups. Centres: 9 centres in Poland. Indication: Primary immunisation of healthy infants in the first year of life against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, Neisseria meningitidis serogroup C. Treatment: The 3 groups in the study were as follows: Hepta + 10Pn Group: Subjects received 3 doses of DTPa-HBV-IPV/Hib-MenC-TT and 10Pn at 2, 3 and 4 months of age and 2 doses of HRV at 2 and 3 months of age. Hexa + MenC Group: Subjects received 3 doses of DTPa-HBV-IPV/Hib at 2, 3 and 4 months of age, 2 doses of MenC- CRM at 3 and 4 months of age and 2 doses of HRV at 2 and 3 months of age. Hexa + 10Pn Group: Subjects in this group received 3 doses of DTPa-HBV-IPV/Hib and 10Pn at 2, 3 and 4 months of age and 2 doses of HRV at 2 and 3 months of age. DTPa-HBV-IPV/Hib-MenC-TT and DTPa-HBV-IPV/Hib were administered intramuscularly in right thigh, 10Pn and MenC-CRM were administered intramuscularly in left thigh and HRV was administered orally. Objectives: To demonstrate that DTPa-HBV-IPV/Hib-MenC-TT co-administered with 10Pn, is non-inferior to DTPa-HBV-IPV/Hib coadministered with MenC-CRM, in terms of seroprotection to MenC one month after the third dose of primary vaccination. Non-inferiority for MenC was demonstrated if the upper limit of the 95% confidence interval (CI) on the group difference (Hexa + MenC Group minus Hepta + 10Pn Group) in the percentage of seroprotected subjects was 10%. To demonstrate that DTPa-HBV-IPV/Hib-MenC-TT co-administered with 10Pn, is non-inferior to DTPa-HBV-IPV/Hib coadministered with 10 Pn, in terms of seroprotection to Hib one month after the third dose of primary vaccination. Non-inferiority for Hib was demonstrated if the upper limit of the 95% CI on the group difference (Hexa + 10Pn Group minus Hepta + 10Pn Group) in percentage of seroprotected subjects was 10%. Primary Outcome/Efficacy Variable: Immunogenicity one month after the third dose of primary vaccination: Anti-Polyribosyl-Ribitol-Phosphate (Anti-PRP) seroprotection status. Serum bactericidal assay against Neisseria meningitidis serogroup C using baby rabbit complement (rsba-menc) seroprotection status. Secondary Outcome/Efficacy Variable(s): Immunogenicity one month after the third dose of primary vaccination: Anti-PRP, rsba-menc, anti-polysaccharide Neisseria meningitides serogroup C (anti-psc), anti-tetanus, anti-diphtheria, anti-pertussis toxoid (anti-pt), anti-filamentous haemagglutinin (anti-fha), anti-pertactin (anti-prn), anti-hepatitis B surface antigen (anti-hbs), anti-poliovirus type 1, anti-poliovirus type 2, anti-poliovirus type 3 and anti-pneumococcal

serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F and protein D (PD) antibody concentrations or titres, and seroprotection or seropositivity status. Vaccine response to PT, FHA and PRN. Immunogenicity before the first vaccine dose of primary vaccination: Anti-PRP, rsba-menc, anti-psc, PT, FHA and PRN antibody concentrations or titres. Safety: Occurrence of solicited local and general symptoms during the 8-day (Day 0-Day 7) follow-up period after each vaccination. Occurrence of unsolicited symptoms during the 31-day (Day 0-Day 30) follow-up period after each vaccination. Occurrence of serious adverse events (SAEs) from Dose 1 up to study end. Statistical Methods: The analyses were performed on the Total Vaccinated Cohort and the According-to-Protocol (ATP) cohort for immunogenicity. The Total Vaccinated Cohort included all vaccinated subjects for whom data were available. The ATP cohort for immunogenicity included all evaluable subjects (who met all eligibility criteria in this study, complied with the procedures and intervals defined in the protocol) for whom immunogenicity data were available. These included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component at the post-primary vaccination blood-sampling time point. Analysis of Immunogenicity: The analyses were performed on the ATP cohort for immunogenicity. Inferential analysis: The 95% CIs in terms of seroprotection for rsba-men C and anti-prp antibodies titres were computed. The objective of noninferiority of DTPa-HBV-IPV/Hib-MenC-TT co-administered with 10Pn was reached if the upper limit of the 95% confidence interval (CI) on the group difference (Hexa + MenC Group minus Hepta + 10Pn Group) in the percentage of seroprotected subjects was 10%. Descriptive analyses: For each group, at each time point and for each antigen for which a serological result was available, serpositivity/seroprotection/vaccine response rates with exact 95% CIs and geometric mean antibody concentrations (GMCs) or geometric mean antibody titres (GMTs) with 95% CIs were tabulated. Seroprotection status: Anti-PRP antibody concentrations 0.15 µg/ml. rsba-menc antibody titres 1:8. Anti-diphtheria antibody concentrations 0.1 IU/mL. Anti-tetanus antibody concentrations 0.1 IU/mL. Anti-HBs antibody concentrations 10* miu/ml. Anti-poliovirus types 1, 2 and 3 antibody titres 1:8. Seropositivity status: Anti-PT, anti-fha and anti-prn antibody concentrations 5 EL.U/mL. Anti-HBs antibody concentrations 3.3 miu/ml. Anti-PSC antibody concentrations 0.3 µg/ml. serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.05 µg/ml. Anti-PD antibody concentrations 100 EL.U/mL. The following other cut-offs were also used: Anti-PSC antibody concentrations 2 µg/ml. Anti-PRP antibody concentrations 1 µg/ml. rsba-menc antibody titres 1:128. serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.2 µg/ml. Vaccine response to PT, FHA and PRN, was defined as the appearance of antibodies in subjects who were initially seronegative (i.e. with concentrations < cut-off value) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e. with concentrations cut-off value), taking into consideration the decreasing maternal antibodies. A decrease in the specificity of the anti-hb ELISA assay had been observed in some studies for low levels of antibody (10-100 miu/ml). The table shows updated results following partial or complete retesting/reanalysis. Some of the available blood samples initially tested with ELISA were re-tested using the new assay, CLIA.

Analysis of Safety: The analysis was performed on the Total vaccinated Cohort. The incidence of solicited local and general symptom occurring during the 8-day (Day 0-Day 7) follow-up period after each vaccination was tabulated with exact 95% CI for each treatment group. The same tabulations were performed for Grade 3 symptoms and for solicited general symptoms assessed by the investigators as related to vaccination. The percentage of subjects with at least one report of an unsolicited adverse event (AE) classified by to Medical Dictionary for Regulatory Activities (MedDRA) preferred term and reported during the 31-day (Day 0-Day 30) follow-up period after each vaccination was tabulated. SAEs were collected and summarised during the entire study period according to MedDRA preferred term. Study Population: Healthy male and female infants aged between, and including 8 and 12 weeks at the time of the first vaccination and had received one dose of hepatitis B (HBV) vaccination at birth as per local recommendations were enrolled in the study. Written informed consent was obtained from the parents/legally Acceptable Representative (LAR) of the subjects. Number of subjects Hepta + 10Pn Group Hexa + MenC Group Hexa + 10Pn Group Planned, N 140 140 140 Randomised, N (Total Vaccinated Cohort) 141 139 141 Completed, n (%) 138 (97.9) 136 (97.8) 139 (98.6) Total Number Subjects Withdrawn, n (%) 3 (2.1) 3 (2.2) 2 (1.4) Withdrawn due to Adverse Events, n (%) 1 (0.7) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not applicable Not applicable Not applicable Withdrawn for other reasons, n (%) 2 (1.4) 3 (2.2) 2 (1.4) Demographics Hepta + 10Pn Group Hexa + MenC Group Hexa + 10Pn Group N (Total Vaccinated Cohort) 141 139 141 Females:Males 74:67 86:53 68:73 Mean Age, weeks (SD) 8.5 (0.98) 8.7 (1.02) 8.7 (1.13) White-Caucasian/European Heritage, n (%) 141 (100) 139 (100) 141 (100) Primary Efficacy Results: Difference between groups Hexa + MenC and Hepta + 10Pn, in percentage of subjects with rsba-menc titres 1:8 one month after the third dose of vaccination (ATP cohort for immunogenicity) Difference in percentage (Hexa + MenC minus Hepta + 10Pn) Hexa + MenC Hepta + 10Pn 95% CI Antibody Cut-off N n % N n % % LL UL rsba-menc 1:8 130 127 97.7 126 124 98.4-0.72-5.19 3.57* n (%) = number (percentage) of subjects with titre within the specified range 95% CI = Standardized asymptotic 95% confidence interval; LL = lower limit, UL = upper limit * Criterion for non inferiority = Upper limit of the 95% CI 10% Primary Efficacy Results: Difference between groups Hexa + 10Pn and Hepta + 10Pn, in percentage of subjects with anti- PRP concentrations 0.15 µg/ml one month after the third dose of vaccination (ATP cohort for immunogenicity) Difference in percentage (Hexa + 10Pn minus Hepta + 10Pn) Hexa + 10Pn Hepta + 10Pn 95% CI Antibody Cut-off N n % N n % % LL UL Anti-PRP 0.15 131 130 99.2 126 126 100-0.76-4.21 2.22* n (%) = number (percentage) of subjects with titre within the specified range 95% CI = Standardized asymptotic 95% confidence interval; LL = lower limit, UL = upper limit * Criterion for non inferiority = Upper limit of the 95% CI 10% Primary Efficacy Results: Percentage of subjects with anti-prp antibody concentrations 0.15 µg/ml, 1.0 µg/ml and GMCs before and one month after primary vaccination (ATP cohort for immunogenicity) 0.15 µg/ml* 1.0 µg/ml GMC (µg/ml) Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-PRP Hepta + 10Pn Pre 124 64 51.6 42.5 60.7 15 12.1 6.9 19.2 0.197 0.162 0.240 Post* 126 126 100 97.1 100 114 90.5 84.0 95.0 4.255 3.591 5.043 Hexa + MenC Pre 127 45 35.4 27.2 44.4 10 7.9 3.8 14.0 0.152 0.125 0.184

Post* 132 123 93.2 87.5 96.8 69 52.3 43.4 61.0 1.123 0.890 1.416 Hexa + 10Pn Pre 127 55 43.3 34.5 52.4 13 10.2 5.6 16.9 0.176 0.143 0.217 Post* 131 130 99.2 95.8 100 84 64.1 55.3 72.3 1.721 1.383 2.143 Pre = Pre-primary blood sample time-point. * Primary efficacy result Primary Efficacy Results: Percentage of subjects with rsba-menc antibody titres 1:8, 1:128 and GMTs before and one month after primary vaccination (ATP cohort for immunogenicity) 1:8* 1:128 GMT Antibody Group Timing N n % LL UL n % LL UL value LL UL rsba- Hepta + 10Pn Pre 118 4 3.4 0.9 8.5 0 0.0 0.0 3.1 4.3 4.0 4.7 MenC Post* 126 124 98.4 94.4 99.8 119 94.4 88.9 97.7 786.9 637.2 971.9 Hexa + MenC Pre 119 8 6.7 2.9 12.8 3 2.5 0.5 7.2 4.8 4.2 5.5 Post* 130 127 97.7 93.4 99.5 127 97.7 93.4 99.5 2674.0 2125.1 3364.7 Hexa + 10Pn Pre 120 3 2.5 0.5 7.1 0 0.0 0.0 3.0 4.2 4.0 4.5 Post 128 10 7.8 3.8 13.9 9 7.0 3.3 12.9 6.1 4.7 8.0 GMT = geometric mean antibody titre calculated on all subjects n (%) = number (percentage) of subjects with titre within the specified range Pre = Pre-primary blood sample time-point. * Primary efficacy result Secondary Outcome Variable(s): Percentage of subjects with anti-psc antibody concentrations 0.3 µg/ml, 2.0 µg/ml and GMCs before and one month after primary vaccination (ATP cohort for immunogenicity) 0.3 µg/ml 2.0 µg/ml GMC (µg/ml) Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-PSC Hepta + 10Pn Pre 122 9 7.4 3.4 13.5 2 1.6 0.2 5.8 0.17 0.16 0.19 Post 125 124 99.2 95.6 100 124 99.2 95.6 100 19.15 16.88 21.74 Hexa + MenC Pre 121 10 8.3 4.0 14.7 2 1.7 0.2 5.8 0.17 0.16 0.19 Post 126 125 99.2 95.7 100 125 99.2 95.7 100 18.10 15.91 20.59 Hexa + 10Pn Pre 126 14 11.1 6.2 17.9 1 0.8 0.0 4.3 0.18 0.16 0.20 Post 132 8 6.1 2.7 11.6 6 4.5 1.7 9.6 0.19 0.16 0.22 Pre = Pre-primary blood sample time-point. Secondary Outcome Variable(s): Seroprotection rates and GMCs for anti-tetanus and anti-diphtheria antibodies one month after primary vaccination (ATP cohort for immunogenicity) 0.1 IU/mL GMC (IU/mL ) 95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL Anti-tetanus Hepta + 10Pn Post 126 126 100 97.1 100 3.966 3.650 4.309 Hexa + MenC Post 132 132 100 97.2 100 1.595 1.422 1.790 Hexa + 10Pn Post 132 132 100 97.2 100 2.458 2.198 2.750 Anti-diphtheria Hepta + 10Pn Post 126 126 100 97.1 100 1.671 1.471 1.899 Hexa + MenC Post 132 132 100 97.2 100 1.437 1.286 1.606 Hexa + 10Pn Post 132 132 100 97.2 100 1.421 1.270 1.591

Secondary Outcome Variable(s): Seropositivity rates and GMCs for anti-pt, anti-fha, anti-prn antibodies before and one month after primary vaccination (ATP cohort for immunogenicity) 5 EL.U/mL GMC (EL.U/mL) 95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL Anti-PT Hepta + 10Pn Pre 123 27 22.0 15.0 30.3 3.5 3.1 4.0 Post 127 127 100 97.1 100 36.1 32.8 39.8 Hexa + MenC Pre 129 31 24.0 16.9 32.3 3.6 3.1 4.0 Post 132 132 100 97.2 100 41.7 37.4 46.4 Hexa + 10Pn Pre 129 32 24.8 17.6 33.2 3.8 3.3 4.4 Post 132 132 100 97.2 100 37.6 34.2 41.4 Anti-FHA Hepta + 10Pn Pre 125 103 82.4 74.6 88.6 12.9 10.7 15.6 Post 127 127 100 97.1 100 110.9 98.1 125.4 Hexa + MenC Pre 130 91 70.0 61.3 77.7 11.9 9.5 14.9 Post 131 131 100 97.2 100 136.4 121.3 153.5 Hexa + 10Pn Pre 127 96 75.6 67.2 82.8 13.2 10.6 16.5 Post 132 132 100 97.2 100 112.7 100.9 126.0 Anti-PRN Hepta + 10Pn Pre 127 55 43.3 34.5 52.4 5.3 4.4 6.4 Post 126 126 100 97.1 100 70.3 59.6 82.8 Hexa + MenC Pre 131 44 33.6 25.6 42.4 4.3 3.7 5.1 Post 132 132 100 97.2 100 107.4 93.0 124.2 Hexa + 10Pn Pre 132 57 43.2 34.6 52.1 5.4 4.5 6.5 Post 131 131 100 97.2 100 90.4 78.1 104.6 Pre = Pre-primary blood sample time-point. Secondary Outcome Variable(s): Vaccine response to PT, FHA and PRN antigens one month after primary vaccination (ATP cohort for immunogenicity) Vaccine response 95% CI Antibody Group Pre-vaccination status N n % LL UL Anti-PT Hepta + 10Pn S- 96 96 100 96.2 100 S+ 27 25 92.6 75.7 99.1 Total 123 121 98.4 94.2 99.8 Hexa + MenC S- 98 98 100 96.3 100 S+ 31 26 83.9 66.3 94.5 Total 129 124 96.1 91.2 98.7 Hexa + 10Pn S- 97 97 100 96.3 100 S+ 32 25 78.1 60.0 90.7 Total 129 122 94.6 89.1 97.8 Anti-FHA Hepta + 10Pn S- 22 22 100 84.6 100 S+ 103 94 91.3 84.1 95.9 Total 125 116 92.8 86.8 96.7 Hexa + MenC S- 39 39 100 91.0 100 S+ 90 84 93.3 86.1 97.5 Total 129 123 95.3 90.2 98.3 Hexa + 10Pn S- 31 31 100 88.8 100

S+ 96 89 92.7 85.6 97.0 Total 127 120 94.5 89.0 97.8 Anti-PRN Hepta + 10Pn S- 72 72 100 95.0 100 S+ 54 40 74.1 60.3 85.0 Total 126 112 88.9 82.1 93.8 Hexa + MenC S- 87 87 100 95.8 100 S+ 44 36 81.8 67.3 91.8 Total 131 123 93.9 88.3 97.3 Hexa + 10Pn S- 75 75 100 95.2 100 S+ 56 48 85.7 73.8 93.6 Total 131 123 93.9 88.3 97.3 Vaccine response defined as : For initially seronegative subjects, antibody concentration 5 EL.U/mL one month after primary vaccination For initially seropositive subjects : antibody concentration one month after primary vaccination 1 fold the pre- vaccination antibody concentration N = number of subjects with both pre- and post-vaccination results available n (%) = number (percentage) of responders 95% CI = exact 95% confidence interval, LL = Lower Limit, UL = Upper Limit S- = seronegative subjects (antibody concentration < 5 EL.U/mL for Anti-PT, Anti-FHA, Anti-PRN) prior to vaccination S+ = seropositive subjects (antibody concentration 5 EL.U/mL for Anti-PT, Anti-FHA, Anti-PRN) prior to vaccination Total = subjects either seropositive or seronegative at pre-vaccination Secondary Outcome Variable(s): Percentage of subjects with anti-hbs antibody concentrations 3.3 miu/ml, 10 miu/ml, 100 miu/ml and GMCs one month after primary vaccination (ATP cohort for immunogenicity) 3.3 miu/ml 10 miu/ml 100 miu/ml GMC (miu/ml) 95% CI Antibody Group Timing N n % LL UL n % LL UL n % LL UL value LL UL Anti-HBs Hepta + Post 116 116 100 96.9 100 116 100 96.9 100 114 98.3 93.9 99.8 1001.4 826.1 1213.9 10Pn Hexa + Post 124 124 100 97.1 100 124 100 97.1 100 122 98.4 94.3 99.8 1187.7 997.8 1413.7 MenC Hexa + 10Pn Post 122 122 100 97.0 100 122 100 97.0 100 120 98.4 94.2 99.8 1073.2 886.3 1299.5 A decrease in the specificity of the anti-hb ELISA assay had been observed in some studies for low levels of antibody (10-100 miu/ml). The table shows updated results following partial or complete retesting/reanalysis. Some of the available blood samples initially tested with ELISA were re-tested using the new assay, CLIA. Secondary Outcome Variable(s): Seroprotection rates and GMTs for anti-poliovirus type 1, anti-poliovirus type 2 and antipoliovirus type 3 antibodies one month after primary vaccination (ATP cohort for immunogenicity) 1:8 GMT 95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL Anti-poliovirus type 1 Hepta + 10Pn Post 91 91 100 96.0 100 132.3 104.7 167.3 Hexa + MenC Post 103 103 100 96.5 100 156.7 127.2 193.0 Hexa + 10Pn Post 92 92 100 96.1 100 126.2 98.9 161.0 Anti-poliovirus type 2 Hepta + 10Pn Post 91 90 98.9 94.0 100 97.4 74.0 128.1 Hexa + MenC Post 103 101 98.1 93.2 99.8 104.3 80.8 134.7 Hexa + 10Pn Post 92 91 98.9 94.1 100 95.8 74.4 123.3 Anti-poliovirus type 3 Hepta + 10Pn Post 90 90 100 96.0 100 275.6 218.2 348.1 Hexa + MenC Post 102 102 100 96.4 100 313.1 250.7 391.0 Hexa + 10Pn Post 91 91 100 96.0 100 257.1 203.8 324.3

GMT = geometric mean antibody titre calculated on all subjects n (%) = number (percentage) of subjects with titre within the specified range Secondary Outcome Variable(s): Percentage of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.05 µg/ml, 0.2 µg/ml and GMCs one month after primary vaccination (ATP cohort for immunogenicity) 0.05 µg/ml 0.2 µg/ml GMC (µg/ml ) Antibody Group Timing N n % LL UL n % LL UL value LL UL serotype 1 serotype 4 serotype 5 serotype 6B serotype 7F serotype 9V Anti- pneumococcal serotype 14 serotype 18C serotype 19F Hepta + 10Pn Post 125 125 100 97.1 100 125 100 97.1 100 1.53 1.36 1.72 Hexa + MenC Post 123 37 30.1 22.1 39.0 12 9.8 5.1 16.4 0.04 0.04 0.05 Hexa + 10Pn Post 125 124 99.2 95.6 100 122 97.6 93.1 99.5 1.41 1.20 1.65 Hepta + 10Pn Post 122 122 100 97.0 100 121 99.2 95.5 100 1.92 1.66 2.22 Hexa + MenC Post 119 21 17.6 11.3 25.7 7 5.9 2.4 11.7 0.04 0.03 0.04 Hexa + 10Pn Post 128 127 99.2 95.7 100 126 98.4 94.5 99.8 1.99 1.69 2.33 Hepta + 10Pn Post 126 126 100 97.1 100 126 100 97.1 100 2.23 1.99 2.50 Hexa + MenC Post 111 44 39.6 30.5 49.4 10 9.0 4.4 15.9 0.05 0.04 0.06 Hexa + 10Pn Post 127 126 99.2 95.7 100 126 99.2 95.7 100 2.23 1.90 2.61 Hepta + 10Pn Post 119 114 95.8 90.5 98.6 89 74.8 66.0 82.3 0.40 0.32 0.49 Hexa + MenC Post 120 28 23.3 16.1 31.9 5 4.2 1.4 9.5 0.04 0.03 0.04 Hexa + 10Pn Post 126 117 92.9 86.9 96.7 100 79.4 71.2 86.1 0.44 0.35 0.55 Hepta + 10Pn Post 125 125 100 97.1 100 125 100 97.1 100 2.26 2.02 2.53 Hexa + MenC Post 123 56 45.5 36.5 54.8 14 11.4 6.4 18.4 0.06 0.05 0.07 Hexa + 10Pn Post 129 128 99.2 95.8 100 128 99.2 95.8 100 2.24 1.95 2.56 Hepta + 10Pn Post 126 126 100 97.1 100 126 100 97.1 100 2.16 1.90 2.46 Hexa + MenC Post 121 37 30.6 22.5 39.6 13 10.7 5.8 17.7 0.05 0.04 0.06 Hexa + 10Pn Post 127 126 99.2 95.7 100 125 98.4 94.4 99.8 1.99 1.72 2.30 Hepta + 10Pn Post 126 126 100 97.1 100 126 100 97.1 100 3.75 3.23 4.36 Hexa + MenC Post 119 106 89.1 82.0 94.1 65 54.6 45.2 63.8 0.22 0.17 0.28 Hexa + 10Pn Post 128 128 100 97.2 100 127 99.2 95.7 100 3.75 3.26 4.32 Hepta + 10Pn Post 122 122 100 97.0 100 121 99.2 95.5 100 3.83 3.22 4.56 Hexa + MenC Post 111 52 46.8 37.3 56.6 10 9.0 4.4 15.9 0.05 0.04 0.07 Hexa + 10Pn Post 126 126 100 97.1 100 125 99.2 95.7 100 2.51 2.11 2.99 Hepta + 10Pn Post 127 127 100 97.1 100 126 99.2 95.7 100 3.99 3.37 4.72 Hexa + MenC Post 121 88 72.7 63.9 80.4 28 23.1 16.0 31.7 0.10 0.08 0.13 Hexa + 10Pn Post 128 127 99.2 95.7 100 127 99.2 95.7 100 3.86 3.19 4.66 Hepta + 10Pn Post 126 123 97.6 93.2 99.5 107 84.9 77.5 90.7 0.68 0.55 0.84 serotype 23F Hexa + MenC Post 127 34 26.8 19.3 35.4 8 6.3 2.8 12.0 0.04 0.03 0.05 Hexa + 10Pn Post 129 124 96.1 91.2 98.7 105 81.4 73.6 87.7 0.63 0.50 0.79 Secondary Outcome Variable(s): Percentage of subjects with anti-pd concentrations 100 EL.U/mL and GMCs one month after primary vaccination (ATP cohort for immunogenicity) 100 EL.U/mL GMC (EL.U/mL) 95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL Anti-PD Hepta + 10Pn Post 126 126 100 97.1 100 1622.8 1433.4 1837.1 Hexa + MenC Post 129 18 14.0 8.5 21.2 63.3 56.3 71.2 Hexa + 10Pn Post 131 130 99.2 95.8 100 1561.6 1359.2 1794.0

Secondary Outcome Variable(s): Number (percentage) of subjects with solicited local symptom during the 8-day (Days 0 to Day 7) post-vaccination period following each dose and across doses (Total Vaccinated Cohort) Hepta + 10Pn Group Hexa + MenC Group Hexa + 10Pn Group Symptom Intensity N n % LL UL N n % LL UL N n % LL UL Dose 1 Pain Any 140 46 32.9 25.2 41.3 138 35 25.4 18.3 33.5 141 64 45.4 37.0 54.0 Grade 3 140 2 1.4 0.2 5.1 138 7 5.1 2.1 10.2 141 3 2.1 0.4 6.1 Redness Any 140 45 32.1 24.5 40.6 138 40 29.0 21.6 37.3 141 55 39.0 30.9 47.6 >20 mm 140 0 0.0 0.0 2.6 138 2 1.4 0.2 5.1 141 3 2.1 0.4 6.1 Swelling Any 140 31 22.1 15.6 29.9 138 21 15.2 9.7 22.3 141 33 23.4 16.7 31.3 >20 mm 140 14 10.0 5.6 16.2 138 7 5.1 2.1 10.2 141 5 3.5 1.2 8.1 Dose 2 Pain Any 139 42 30.2 22.7 38.6 136 48 35.3 27.3 43.9 140 56 40.0 31.8 48.6 Grade 3 139 2 1.4 0.2 5.1 136 4 2.9 0.8 7.4 140 4 2.9 0.8 7.2 Redness Any 139 51 36.7 28.7 45.3 136 63 46.3 37.7 55.1 140 61 43.6 35.2 52.2 >20 mm 139 1 0.7 0.0 3.9 136 3 2.2 0.5 6.3 140 6 4.3 1.6 9.1 Swelling Any 139 41 29.5 22.1 37.8 136 36 26.5 19.3 34.7 140 49 35.0 27.1 43.5 >20 mm 139 7 5.0 2.0 10.1 136 7 5.1 2.1 10.3 140 13 9.3 5.0 15.4 Dose 3 Pain Any 138 30 21.7 15.2 29.6 136 35 25.7 18.6 33.9 139 47 33.8 26.0 42.3 Grade 3 138 2 1.4 0.2 5.1 136 0 0.0 0.0 2.7 139 4 2.9 0.8 7.2 Redness Any 138 54 39.1 30.9 47.8 136 65 47.8 39.2 56.5 139 60 43.2 34.8 51.8 >20 mm 138 5 3.6 1.2 8.3 136 7 5.1 2.1 10.3 139 4 2.9 0.8 7.2 Swelling Any 138 44 31.9 24.2 40.4 136 42 30.9 23.2 39.4 139 56 40.3 32.1 48.9 >20 mm 138 7 5.1 2.1 10.2 136 8 5.9 2.6 11.3 139 12 8.6 4.5 14.6 Across Doses Pain Any 140 66 47.1 38.7 55.8 138 70 50.7 42.1 59.3 141 85 60.3 51.7 68.4 Grade 3 140 6 4.3 1.6 9.1 138 9 6.5 3.0 12.0 141 8 5.7 2.5 10.9 Redness Any 140 83 59.3 50.7 67.5 138 81 58.7 50.0 67.0 141 83 58.9 50.3 67.1 >20 mm 140 6 4.3 1.6 9.1 138 11 8.0 4.0 13.8 141 9 6.4 3.0 11.8 Swelling Any 140 64 45.7 37.3 54.3 138 50 36.2 28.2 44.8 141 71 50.4 41.8 58.9 >20 mm 140 19 13.6 8.4 20.4 138 15 10.9 6.2 17.3 141 20 14.2 8.9 21.1 N= number of subjects with at least one documented dose n (%) = number (percentage) of subjects reporting a specified symptom 95%CI, LL and UL = Exact 95% confidence interval, lower and upper limit Any = Incidence of a local symptom irrespective of intensity grade Grade 3 pain = cried when limb was moved/spontaneously painful Secondary Outcome Variable(s): Number (percentage) of subjects with solicited general symptoms during the 8-day (Days 0-7) following each dose and across doses (Total Vaccinated Cohort) Hepta + 10Pn Group Hexa + MenC Group Hexa + 10Pn Group Symptom Intensity/ Relationship N n % LL UL N n % LL UL N n % LL UL Dose 1 Drowsiness Any 140 83 59.3 50.7 67.5 138 76 55.1 46.4 63.5 141 85 60.3 51.7 68.4 Grade 3 140 1 0.7 0.0 3.9 138 4 2.9 0.8 7.3 141 3 2.1 0.4 6.1 Related 140 75 53.6 45.0 62.0 138 72 52.2 43.5 60.7 141 77 54.6 46.0 63.0 Irritability Any 140 83 59.3 50.7 67.5 138 75 54.3 45.7 62.8 141 99 70.2 61.9 77.6 Grade 3 140 10 7.1 3.5 12.7 138 12 8.7 4.6 14.7 141 17 12.1 7.2 18.6 Related 140 77 55.0 46.4 63.4 138 69 50.0 41.4 58.6 141 90 63.8 55.3 71.7 Loss of appetite Any 140 53 37.9 29.8 46.4 138 40 29.0 21.6 37.3 141 51 36.2 28.3 44.7 Grade 3 140 1 0.7 0.0 3.9 138 2 1.4 0.2 5.1 141 0 0.0 0.0 2.6

Temperature (Axillary) Related 140 48 34.3 26.5 42.8 138 36 26.1 19.0 34.2 141 49 34.8 26.9 43.2 37.5 C 140 36 25.7 18.7 33.8 138 16 11.6 6.8 18.1 141 38 27.0 19.8 35.1 >39.0 C 140 0 0.0 0.0 2.6 138 0 0.0 0.0 2.6 141 0 0.0 0.0 2.6 Related 140 34 24.3 17.4 32.2 138 14 10.1 5.7 16.4 141 34 24.1 17.3 32.0 Dose 2 Drowsiness Any 139 59 42.4 34.1 51.1 136 54 39.7 31.4 48.4 140 63 45.0 36.6 53.6 Grade 3 139 1 0.7 0.0 3.9 136 5 3.7 1.2 8.4 140 3 2.1 0.4 6.1 Related 139 53 38.1 30.0 46.7 136 51 37.5 29.4 46.2 140 60 42.9 34.5 51.5 Irritability Any 139 74 53.2 44.6 61.7 136 66 48.5 39.9 57.2 140 89 63.6 55.0 71.5 Grade 3 139 7 5.0 2.0 10.1 136 8 5.9 2.6 11.3 140 12 8.6 4.5 14.5 Related 139 69 49.6 41.1 58.2 136 61 44.9 36.3 53.6 140 86 61.4 52.8 69.5 Loss of appetite Temperature (Axillary) Any 139 31 22.3 15.7 30.1 136 34 25.0 18.0 33.1 140 44 31.4 23.9 39.8 Grade 3 139 2 1.4 0.2 5.1 136 0 0.0 0.0 2.7 140 0 0.0 0.0 2.6 Related 139 26 18.7 12.6 26.2 136 33 24.3 17.3 32.4 140 42 30.0 22.6 38.3 37.5 C 139 26 18.7 12.6 26.2 136 16 11.8 6.9 18.4 140 31 22.1 15.6 29.9 >39.0 C 139 0 0.0 0.0 2.6 136 0 0.0 0.0 2.7 140 0 0.0 0.0 2.6 Related 139 22 15.8 10.2 23.0 136 13 9.6 5.2 15.8 140 29 20.7 14.3 28.4 Dose 3 Drowsiness Any 138 42 30.4 22.9 38.8 136 39 28.7 21.3 37.1 139 48 34.5 26.7 43.1 Grade 3 138 2 1.4 0.2 5.1 136 3 2.2 0.5 6.3 139 0 0.0 0.0 2.6 Related 138 39 28.3 20.9 36.5 136 34 25.0 18.0 33.1 139 41 29.5 22.1 37.8 Irritability Any 138 66 47.8 39.3 56.5 136 49 36.0 28.0 44.7 139 63 45.3 36.9 54.0 Grade 3 138 5 3.6 1.2 8.3 136 4 2.9 0.8 7.4 139 5 3.6 1.2 8.2 Related 138 58 42.0 33.7 50.7 136 41 30.1 22.6 38.6 139 58 41.7 33.4 50.4 Loss of appetite Temperature (Axillary) Any 138 23 16.7 10.9 24.0 136 29 21.3 14.8 29.2 139 32 23.0 16.3 30.9 Grade 3 138 0 0.0 0.0 2.6 136 2 1.5 0.2 5.2 139 1 0.7 0.0 3.9 Related 138 22 15.9 10.3 23.1 136 23 16.9 11.0 24.3 139 30 21.6 15.1 29.4 37.5 C 138 22 15.9 10.3 23.1 136 16 11.8 6.9 18.4 139 23 16.5 10.8 23.8 >39.0 C 138 0 0.0 0.0 2.6 136 1 0.7 0.0 4.0 139 0 0.0 0.0 2.6 Related 138 21 15.2 9.7 22.3 136 13 9.6 5.2 15.8 139 21 15.1 9.6 22.2 Across Doses Drowsiness Any 140 105 75.0 67.0 81.9 138 91 65.9 57.4 73.8 141 107 75.9 68.0 82.7 Grade 3 140 4 2.9 0.8 7.2 138 9 6.5 3.0 12.0 141 6 4.3 1.6 9.0 Related 140 97 69.3 60.9 76.8 138 87 63.0 54.4 71.1 141 100 70.9 62.7 78.3 Irritability Any 140 108 77.1 69.3 83.8 138 101 73.2 65.0 80.4 141 113 80.1 72.6 86.4 Grade 3 140 17 12.1 7.2 18.7 138 17 12.3 7.3 19.0 141 28 19.9 13.6 27.4 Related 140 102 72.9 64.7 80.0 138 93 67.4 58.9 75.1 141 108 76.6 68.7 83.3 Loss of appetite Any 140 72 51.4 42.8 60.0 138 62 44.9 36.5 53.6 141 72 51.1 42.5 59.6 Grade 3 140 3 2.1 0.4 6.1 138 4 2.9 0.8 7.3 141 1 0.7 0.0 3.9 Related 140 66 47.1 38.7 55.8 138 58 42.0 33.7 50.7 141 68 48.2 39.7 56.8 Temperature 37.5 C 140 53 37.9 29.8 46.4 138 38 27.5 20.3 35.8 141 61 43.3 35.0 51.9 (Axillary) >39.0 C 140 0 0.0 0.0 2.6 138 1 0.7 0.0 4.0 141 0 0.0 0.0 2.6 Related 140 50 35.7 27.8 44.2 138 34 24.6 17.7 32.7 141 54 38.3 30.2 46.9 N= number of subjects with at least one documented dose n (%)= number (percentage) of subjects reporting at least once the symptom 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = Incidence of a general symptom irrespective of intensity grade and relationship to vaccination Grade 3 drowsiness = drowsiness that prevented normal activity Grade 3 irritability = crying that could not be comforted/prevented normal activity Grade 3 loss of appetite = did not eat at all Related = symptoms assessed by the investigator as causally related to vaccination Safety results: Number (%) of subjects with unsolicited adverse events within the 31-day (Days 0-30) post-vaccination period (Total Vaccinated Cohort) Most frequent adverse events - On-Therapy (occurring within Day 0 to Day 30 following vaccination) Hepta + 10Pn Group Hexa + MenC Group N = 139 Hexa + 10Pn Group

Subjects with any AE(s), n (%) 61 (43.3) 52 (37.4) 61 (43.3) Rhinitis 11 (7.8) 18 (12.9) 17 (12.1) Upper respiratory tract infection 10 (7.1) 7 (5.0) 10 (7.1) Bronchitis 3 (2.1) 6 (4.3) 7 (5.0) Nasopharyngitis 9 (6.4) 4 (2.9) - Viral infection 4 (2.8) 3 (2.2) 4 (2.8) Dermatitis allergic 3 (2.1) 2 (1.4) 4 (2.8) Urinary tract infection 4 (2.8) - 4 (2.8) Diarrhoea - - 6 (4.3) Pharyngitis 4 (2.8) 2 (1.4) - Weight gain poor 3 (2.1) - 3 (2.1) Conjunctivitis - 5 (3.6) - Otitis media - 2 (1.4) 3 (2.1) Dermatitis atopic 3 (2.1) - - Hypochromic anaemia - - 3 (2.1) Milk allergy 3 (2.1) - - Rash 3 (2.1) - - Candidiasis - 2 (1.4) - Cough - 2 (1.4) - Counting rule applied: As there were more than 30 subjects per treatment group and 3 groups, only the 10 most frequent events in each treatment group are to be listed. -: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 10 most frequent events for that group. Safety results: Number (%) of subjects with serious adverse events during the entire study period (Total Vaccinated Cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs Hepta + 10Pn Group Hexa + MenC Group N = 139 Hexa + 10Pn Group Subjects with any SAE(s), n (%) [n assessed by 5 (3.5) [1] 6 (4.3) [0] 3 (2.1) [0] the investigator as related] Bronchopneumonia 2 (1.4) [0] 1 (0.7) [0] 0 (0.0) [0] Bronchitis 1 (0.7) [0] 1 (0.7) [0] 0 (0.0) [0] Urinary tract infection 1 (0.7) [0] 1 (0.7) [0] 0 (0.0) [0] Abdominal pain 0 (0.0) [0] 1 (0.7) [0] 0 (0.0) [0] Aspiration 1 (0.7) [0] 0 (0.0) [0] 0 (0.0) [0] Bronchiolitis 0 (0.0) [0] 1 (0.7) [0] 0 (0.0) [0] Diarrhoea 0 (0.0) [0] 0 (0.0) [0] 1 (0.7) [0] Gastroenteritis 0 (0.0) [0] 0 (0.0) [0] 1 (0.7) [0] Otitis media 0 (0.0) [0] 1 (0.7) [0] 0 (0.0) [0] Pharyngitis 0 (0.0) [0] 1 (0.7) [0] 0 (0.0) [0] Pyelonephritis 0 (0.0) [0] 0 (0.0) [0] 1 (0.7) [0] Thrombocytopenia 1 (0.7) [1] 0 (0.0) [0] 0 (0.0) [0] Fatal SAEs Hepta + 10Pn Group Hexa + MenC Group Hexa + 10Pn Group Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related] N = 139 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Conclusion: One month after primary vaccination, 100% of subjects in Hepta + 10Pn Group, 93.2% of subjects in Hexa + MenC Group and 99.2% of subjects in Hexa + 10Pn Group had anti-prp antibody concentrations 0.15 µg/ml. At the same time point, 98.4% of the subjects in the Hepta + 10Pn Group and 97.7% of the subjects in the Hexa + MenC Group had rsba-menc antibody titres 1:8. Within the 31-day (Days 0-30) post-vaccination period, at least one unsolicited AE was reported for 61 (43.3%) subjects in the Hepta + 10Pn Group, 52 (37.4%) subjects in the Hexa + MenC Group and 61 (43.3%) subjects in the Hexa + 10Pn Group. During the entire study period, SAEs were reported for 5 subjects in the Hepta + 10Pn Group, 6 subjects in the Hexa + MenC Group and 3 subjects in the Hexa + 10Pn Group. One SAE reported in the Hexa + 10Pn Group was assessed by the investigators as causally related to vaccination. No fatal SAEs were reported during the study period. Date updated: 05-February-2014