the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib

Transcription

1 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. GSK Medicine: GSK A Study No.: (10PN-PD-DIT-004) Title: A phase II, multicentre booster study to evaluate booster vaccination with GSK Biologicals 10-valent pneumococcal conjugate vaccine or to evaluate the immune memory following the administration of a single dose of 23-valent plain polysaccharide vaccine in healthy children, previously vaccinated in infancy in the primary study 11PN-PD-DIT-002 (103488). 10Pn-PD-DiT: GlaxoSmithKline (GSK) Biologicals 10-valent pneumococcal conjugate vaccine Pneumovax 23 (): Sanofi Pasteur MSD s 23-valent polysaccharide pneumococcal vaccine. Rationale: In the primary study, there were 11 groups of which 9 groups received a different formulation of GSK Biologicals conjugate DiT vaccine, one group received the first generation 11Pn-PD vaccine and one group received 7Pn vaccine. Vaccines were administered as a 3-dose primary vaccination course concomitantly with DTPa- HBV-IPV/Hib according to a months of age schedule. Please refer to the CTRS for the results of the primary study. In this booster study, the subjects, previously vaccinated in the primary study , were assigned to receive either a single dose of or 10Pn-PD-DiT vaccine, co-administered with DTPa-HBV-IPV/Hib at month of age. In order to evaluate the induction of immune memory following primary vaccination, a booster dose of vaccine was administered to children primed either with one selected DiT formulation (Formulation F in the CTRS), or with the 11Pn-PD vaccine or the 7Pn vaccine, at months of age, in co-administration with a DTPa-HBV-IPV/Hib booster dose. In order to evaluate the booster immune response to the 10Pn-PD-DiT vaccine, children primed with the 8 other experimental DiT formulations received a booster dose of the 10Pn-PD-DiT vaccine, at months of age, in co-administration with DTPa-HBV-IPV/Hib booster dose. In addition, the persistence of antibodies induced following primary vaccination with the different pneumococcal conjugated formulations, was assessed. The duration of the booster study was approximately 1 month. DiT: GSK Biologicals liquid 11-valent pneumococcal protein D, diphtheria and tetanus toxoids conjugate vaccine.. 11Pn-PD: GSK Biologicals 11-valent pneumococcal-protein D conjugate vaccine (first generation) Prevenar (7Pn): Wyeth s 7-valent pneumococcal conjugate vaccine with diphtheria CRM197 as protein carrier and containing pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. Infanrix hexa (DTPa-HBV-IPV/Hib): GSK Biologicals diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus and Haemophilus influenzae type b (Hib) vaccine. Phase: II Study Period: 17 November 2005 to 13 March Study Design: Open, multi-centric study with 2 parallel groups. Centres: 54 study centres in Germany. Indication: Booster vaccination against Streptococcus pneumoniae in healthy children Treatment: The study groups and sub-groups were as follows: Group consisted of the following sub-groups: - Group: subjects, who had received 11Pn-PD and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of co-administered with DTPa-HBV-IPV/Hib vaccine. - 7Pn- Group: subjects, who had received 7Pn and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of co-administered with DTPa-HBV-IPV/Hib vaccine. - Group: subjects, who had received DiT [Formulation F (Form F)] and DTPa-HBV- IPV/Hib vaccines in the primary study, received the booster dose of co-administered with DTPa-HBV- IPV/Hib vaccine. 10Pn Group consisted of the following sub-groups: - 11Pn-A-10Pn Group: subjects, who had received DiT (Form A) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. - 11Pn-B-10Pn Group: subjects, who had received DiT (Form B) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine.

2 - 11Pn-C-10Pn Group: subjects, who had received DiT (Form C) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. - 11Pn-D-10Pn Group: subjects, who had received DiT (Form D) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. - 11Pn-E-10Pn Group: subjects, who had received DiT (Form E) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. - 11Pn-G-10Pn Group: subjects, who had received DiT (Form G) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. - 11Pn-H-10Pn Group: subjects, who had received DiT (Form H) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. - 11Pn-I-10Pn Group: subjects, who had received DiT (Form I) and DTPa-HBV-IPV/Hib vaccines in the primary study, received the booster dose of 10Pn-PD-DiT co-administered with DTPa-HBV-IPV/Hib vaccine. 10Pn-PD-DiT or vaccine was administered intramuscularly into the right deltoid region, and DTPa-HBV-IPV/Hib vaccine was administered intramuscularly into the left deltoid region. Objectives: To assess the immunological memory following primary vaccination with either selected DiT (Form F)- vaccine formulation or the 11Pn-PD vaccine or the 7Pn vaccine, through the administration of a single dose of vaccine. To assess the immune response of a booster dose of 10Pn-PD-DiT vaccine administered to children months of age following primary vaccination with one of the 8 other DiT vaccine formulations. Primary Outcome/Efficacy Variable: One month after the administration of the booster dose with either 10Pn-PD-DiT vaccine or one month after the administration of the single dose, anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations. Secondary Outcome/Efficacy Variable(s): Immunogenicity: Prior to vaccination in all groups: Antibody concentrations to pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations to protein D (anti-pd). Anti-diphtheria (anti-d) and anti-tetanus toxoids (anti-t), anti-polyribosyl-ribitol-phosphate (anti-prp), anti-pertussis toxoids (anti-pt), anti-filamentous hemagglutinin (anti-fha) and anti-pertactin (anti-prn), anti-hepatitis B surface antigen (anti-hbs) antibody concentrations and anti-polio type 1, 2 and 3 antibody titres. Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.20 µg/ml. One month after the administration of the booster dose with either 10Pn-PD-DiT vaccine or one month after the administration of the single dose of : Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.20 µg/ml. Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Anti-PD antibody concentrations. Anti-D and anti-t, anti-prp, anti-pt, anti-fha and anti-prn, anti-hbs antibody concentrations and anti-polio type 1, 2 and 3 antibody titres. Booster vaccine response to PT, FHA and PRN, defined as appearance of antibodies in subjects who are initially seronegative (i.e., with concentrations < 5 EL.U/mL), and at least two-fold increase of pre-vaccination antibody concentrations in those who are initially seropositive (i.e., with concentrations 5 EL.U/mL). Seropositivity status, defined as: - Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.05 µg/ml. - Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F 8. - Anti-PD antibody concentrations 100 EL.U/mL. - Anti-PT antibody concentrations 5 EL.U/mL. - Anti-FHA antibody concentrations 5 EL.U/mL.

3 - Anti-PRN antibody concentrations 5 EL.U/mL. Seroprotection status, defined as: - Anti-D antibody concentrations 0.1 IU/mL. - Anti-T antibody concentrations 0.1 IU/mL. - Anti-PRP antibody concentrations 0.15 μg/ml. - Anti-PRP antibody concentrations 1.0 μg/ml. - Anti-HBs antibody concentrations 10 miu/ml. - Anti-polio type 1 antibody titres 8. - Anti-polio type 2 antibody titres 8. - Anti-polio type 3 antibody titres 8. Safety: Occurrence of solicited local symptoms (any and grade 3) within 4 days (Days 0-3) after vaccination. Occurrence of solicited general symptoms (any and grade 3) within 4 days (Days 0-3) after vaccination. Occurrence of unsolicited adverse events (AEs) within 31 days (Days 0-30) after vaccination. Occurrence of serious adverse events (SAEs) throughout the whole study period. Statistical Methods: The analyses were performed on the Total Vaccinated cohort, According-To-Protocol (ATP) cohort for persistence and ATP cohort for immunogenicity. - The Total Vaccinated cohort included all subjects with vaccine administration documented. - The ATP cohort for antibody persistence included all subjects who received their vaccine according to their planned assignment, for whom administration site of vaccine was known, who did not receive a vaccine not specified or forbidden in the protocol; for whom assay results were available for antibodies against at least one study vaccine antigen component for the blood sampling taken before the administration of the study booster dose. - The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination. Analysis of pneumococcal antibody persistence: The analysis was performed on the ATP cohort for persistence. Seropositivity rates and geometric mean concentrations (GMCs) were calculated with 95% confidence interval (CI), at post dose 3 (in the primary study) and prior to booster dose for all pneumococcal serotypes and anti-pd antibodies in all 10Pn and sub-groups. Analysis of immune response following booster vaccination: The analysis was performed on the ATP cohort for immunogenicity. For the sub-groups and for the 10Pn Group, seropositivity/seroprotection rates and GMCs/geometric mean titres (GMTs) were calculated with 95% CI prior booster vaccination and post booster vaccination for each serotype/antigen. Vaccine responses to PT, FHA and PRN were also calculated with exact 95% CI for the same groups. Anti-PD antibodies seropositivity and GMCs were tabulated for the 10Pn Group. Analysis of safety: The analysis of safety was performed on the Total Vaccinated cohort. For the sub-groups and the 10Pn Group, the number and percentage of subjects reporting any solicited local and general symptom during the 4-day (Days 0-3) follow-up period after booster vaccination, were tabulated with exact 95% CI. The same tabulation was performed for Grade 3 symptoms and general symptoms assessed by the investigators as causally related to the vaccination. For the same groups, the number and percentage of subjects with at least one unsolicited AEs reported within the 31-day (Days 0-30) following booster vaccination was tabulated according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred term. The number and percentage of subjects with SAEs reported during the entire study period, as well as SAEs assessed by the investigators as related to the vaccination, were also tabulated according to the MedDRA preferred term. Study Population: A male or female between, and including, months of age, who previously participated in the study and received at least one dose of pneumococcal conjugate vaccine during the primary study, without receiving any additional pneumococcal vaccine or DTPa combined vaccine since study end of 11PN-PD-DIT-002 study, and free of obvious health problems as established by medical history and clinical examination before entering into the study. Written informed consent was obtained from the parent or guardian of the subject. Subjects with history or

4 intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b disease, and/or invasive pneumococcal diseases were excluded. Number of Subjects: 10Pn 7Pn- Planned, N Randomised, N (Total Vaccinated cohort) Completed, n (%) 395 (99.5) 49 (98.0) 52 (100) 48 (100) Total Number Subjects Withdrawn, n (%) 2 (0.5) 1 (2.0) 0 (0.0) 0 (0.0) Withdrawn due to Adverse Events, n (%) 1 (0.3) 0 (0.0) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not applicable Not applicable Not applicable Not applicable Withdrawn for other reasons, n (%) 1 (0.3) 1 (2.0) 0 (0.0) 0 (0.0) Demographics 10Pn 7Pn- N (Total Vaccinated cohort) Females: Males 193:204 23:27 28:24 26:22 Mean Age, months (SD) 14.0 (1.23) 14.1 (1.24) 13.8 (1.26) 14.0 (1.34) White-Caucasian/ European heritage, n (%) 384 (96.7) 46 (92.0) 52 (100) 47 (97.9) Primary Efficacy Results: Seropositivity rates and GMCs for anti-1, anti-4, anti-5, anti-6b, anti-7f, anti-9v, anti-14, anti-18c, anti-19f and anti-23f antibody concentrations in the subgroups, measured by 22F-ELISA (ATP cohort for immunogenicity) Antibody Group Timing N 0.05 µg/ml 0.2 µg/ml GMC(µg/mL)* n % 95% CI n % 95% CI value 95% CI LL UL LL UL LL UL Anti-1 Anti-4 Anti-5 Anti-6B PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* PIII(M3) Pre Post* PIII(M3) Pre Post*

5 Anti-7F Anti-9V Anti-14 7Pn- PIII(M3) Pre Post* PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* Anti-18C PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* Anti-19F PIII(M3) Pre Post* PIII(M3) Pre Post* Pn- PIII(M3) Pre Post* Anti-23F PIII(M3) Pre Post* PIII(M3) Pre Post*

6 7Pn- PIII(M3) Pre Post* GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range PIII(M3) = post Dose 3 at Month 3 (primary phase) Post = post-booster vaccination (booster phase) *Primary outcome variable Primary Efficacy Results: Seropositivity rates and GMCs for anti-1, anti-4, anti-5, anti-6b, anti-7f, anti-9v, anti-14, anti-18c, anti-19f and anti-23f antibody concentrations in the 10Pn Group, measured by 22F-ELISA (ATP cohort for immunogenicity) Antibody Group Timing N 0.05 µg/ml 0.2 µg/ml GMC(µg/mL)* n % 95% CI n % 95% CI value 95% CI LL UL LL UL LL UL Anti-1 10Pn PIII(M3) Pre Post* Anti-4 10Pn PIII(M3) Pre Post* Anti-5 10Pn PIII(M3) Pre Post* Anti-6B 10Pn PIII(M3) Pre Post* Anti-7F 10Pn PIII(M3) Pre Post* Anti-9V 10Pn PIII(M3) Pre Post* Anti-14 10Pn PIII(M3) Pre Post* Anti-18C 10Pn PIII(M3) Pre Post* Anti-19F 10Pn PIII(M3) Pre Post* Anti-23F 10Pn PIII(M3) Pre Post* GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range PIII(M3) = post Dose 3 at Month 3 (primary phase) Post = post-booster vaccination (booster phase) *Primary outcome variable

7 Seropositivity rates and GMCs for anti-1, anti-4, anti-5, anti-6b, anti-7f, anti-9v, anti-14, anti-18c, anti-19f and anti-23f antibody concentrations in the 10Pn and sub-groups, measured by 22F-ELISA (ATP cohort for persistence) Antibody Group Timing N 0.05 g/ml 0.2 µg/ml GMC(µg/mL) n % 95% CI n % 95% CI 95% CI LL UL LL UL value LL UL Anti-1 11Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Anti-4 11Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Anti-5 11Pn-A- PIII(M3) Pn Pre Pn-B- 10Pn PIII(M3) Pre

8 Anti-6B Anti-7F 11Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre

9 Anti-9V Anti-14 Anti- 18C 11Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Pn-A- PIII(M3) Pn Pre

10 11Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Anti-19F 11Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre Anti-23F 11Pn-A- PIII(M3) Pn Pre Pn-B- PIII(M3) Pn Pre Pn-C- PIII(M3) Pn Pre Pn-D- PIII(M3) Pn Pre Pn-E- PIII(M3) Pn Pre Pn-G- PIII(M3) Pn Pre

11 11Pn-H- PIII(M3) Pn Pre Pn-I- PIII(M3) Pn Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range PIII(M3) = post Dose 3 at Month 3 (primary phase) Seropositivity rates and GMCs for anti-pd concentrations in the 10Pn and sub-groups (ATP cohort for persistence) Antibody Group Timing N 100 EL.U/mL GMC(EL.U/mL) n % 95% CI value 95% CI LL UL LL UL Anti-PD 11Pn-A-10Pn PIII(M3) Pre Pn-B-10Pn PIII(M3) Pre Pn-C-10Pn PIII(M3) Pre Pn-D-10Pn PIII(M3) Pre Pn-E-10Pn PIII(M3) Pre Pn-G-10Pn PIII(M3) Pre Pn-H-10Pn PIII(M3) Pre Pn-I-10Pn PIII(M3) Pre PIII(M3) Pre PIII(M3) Pre Pn- PIII(M3) Pre GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range PIII(M3) = post Dose 3 at Month 3 (primary phase) Seropositivity rates and GMCs for anti-pd concentrations in the 10Pn Group (ATP cohort for immunogenicity) Antibody Group Timing N 100 EL.U/mL GMC(EL.U/mL) n % 95% CI value 95% CI LL UL LL UL Anti-PD 10Pn PIII(M3)

12 Pre Post GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range PIII(M3) = post Dose 3 (primary phase) Post = post-booster vaccination (booster phase) Seropositivity rates and GMTs for opsono-1, opsono-4, opsono-5, opsono-6b, opsono-7f, opsono-9v, opsono-14, opsono-18c, opsono-19f and opsono-23f antibody titres in the sub-groups (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT n % 95% CI value 95% CI LL UL LL UL Opsono-1 PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post Opsono-4 PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post Opsono-5 PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post Opsono-6B Opsono-7F Opsono-9V PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post

13 Opsono-14 Opsono-18C Opsono- 19F PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post PIII(M3) Post PIII(M3) Post Pn- PIII(M3) Post Opsono- PIII(M3) F Post PIII(M3) Post Pn- PIII(M3) Post GMT = geometric mean titre n (%) = number (percentage) of subjects with titre within the specified range PIII(M3) = post Dose 3 at Month 3 (primary phase) Post = post-booster vaccination (booster phase) Seropositivity rates and GMTs for opsono-1, opsono-4, opsono-5, opsono-6b, opsono-7f, opsono-9v, opsono-14, opsono-18c, opsono-19f and opsono-23f antibody titres in the 10Pn Group (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT n % 95% CI value 95% CI LL UL LL UL Opsono-1 10Pn PIII(M3) Post Opsono-4 10Pn PIII(M3) Post Opsono-5 10Pn PIII(M3) Post Opsono-6B 10Pn PIII(M3) Post Opsono-7F 10Pn PIII(M3) Post Opsono-9V 10Pn PIII(M3) Post Opsono-14 10Pn PIII(M3) Post Opsono-18C 10Pn PIII(M3) Post Opsono- 19F 10Pn PIII(M3) Post

14 Opsono- 10Pn PIII(M3) F Post GMT = geometric mean titre n (%) = number (percentage) of subjects with titre within the specified range PIII(M3) = post Dose 3 at Month 3 (primary phase) Post = post-booster vaccination (booster phase) Seroprotection rates and GMCs for anti-d and anti-t antibodies in the 10Pn Group and the sub-groups (ATP cohort for immunogenicity) Antibody Group Timing N 0.1 IU/mL GMC(IU/mL) n 95% CI value 95% CI % LL UL LL UL Anti-D 10Pn Pre Post Pre Post Pre Post Pn- Pre Post Anti-T 10Pn Pre Post Pre Post Pre Post Pn- Pre Post GMC = geometric mean concentration n (%) = number (percentage) of subjects with titre within the specified range Post = post-booster vaccination (booster phase) Seroprotection rates and GMCs for anti-prp antibodies in the 10Pn Group and the sub-groups (ATP cohort for immunogenicity) Antibody Group Timing N 0.15 µg/ml 1 µg/ml GMC(µg/mL) n % 95% CI n % 95% CI value 95% CI LL UL LL UL LL UL Anti-PRP 10Pn Pre Post Pre Post Pre Post Pn- Pre Post GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range ( 0.15 µg/ml, 1 µg/ml)

15 Post = post-booster vaccination (booster phase) Seropositivity rates and GMCs for anti-pt, anti-fha and anti-prn antibodies in the 10Pn Group and the subgroups (ATP cohort for immunogenicity) Antibody Group Timing N 5 EL.U/mL GMC(EL.U/mL) n % 95% CI value 95% CI LL UL LL UL Anti-PT 10Pn Pre Post Pre Post Pre Post Pn- Pre Post Anti-FHA 10Pn Pre Post Pre Post Pre Post Pn- Pre Post Anti-PRN 10Pn Pre Post Pre Post Pre Post Pn- Pre Post GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range Post = post-booster vaccination (booster phase) Booster immune response for anti-pt, anti-fha and anti-prn antibodies at Post-Booster in the 10Pn Group and the sub-groups (ATP cohort for immunogenicity) Antibody Group Pre-vaccination status N Booster immune response n % 95% CI LL UL Anti-PT 10Pn S S Total S S Total S S Total Pn- S S

16 Total Anti-FHA 10Pn S S Total S S Total S S Total Pn- S S Total Anti-PRN 10Pn S S Total S S Total S S Total Pn- S S Total 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 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 Seroprotection rates and GMCs for anti-hbs antibodies in the 10Pn Group and the sub-groups (ATP cohort for immunogenicity) Antibody Group Timing N 10 miu/ml GMC(mIU/mL) n % 95% CI value 95% CI LL UL LL UL Anti-HBs 10Pn Pre Post Pre Post Pre Post Pn- Pre Post GMC = geometric mean concentration n (%) = number (percentage) of subjects with concentration within the specified range Post = post-booster vaccination (booster phase) Seroprotection rates and GMTs for anti-polio 1, anti-polio 2 and anti-polio 3 antibodies in the 10Pn Group and the sub-groups (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT

17 n % 95% CI value 95% CI LL UL LL UL Anti-polio 1 10Pn Pre Post Pre Post Pre Post Pn- Pre Post Anti-polio 2 10Pn Pre Post Pre Post Pre Post Pn- Pre Post Anti-polio 3 10Pn Pre Post Pre Post Pre Post Pn- Pre Post GMT = geometric mean titre n (%) = number (percentage) of subjects with titre within the specified range Post = post-booster vaccination (booster phase) Incidence of solicited local symptoms reported during the 4-day (Days 0-3) post-vaccination period in the 10Pn Group and the sub-groups (Total Vaccinated cohort) Symptom Intensity N n % 95% CI N n % 95% CI LL UL LL UL 10Pn Pain Any Grade Redness Any >30mm Swelling Any >30mm Pn- Pain Any Grade Redness Any >30mm Swelling Any >30mm N = number of subjects with 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 = any solicited local symptom irrespective of intensity grade