GSK Medicine: Study Number: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment:

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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 GSK A Study Number: (SPNG-009) Title: Immunogenicity and safety study of two formulations of GSK Biologicals pneumococcal vaccine ( A and A) when administered in healthy infants. GSK A (11Pn-PD-DiT-CRM): GlaxoSmithKline (GSK) Biologicals' 11-valent pneumococcal polysaccharide and nontypeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine. GSK A (12Pn-PD-DiT-CRM): GSK Biologicals' 12-valent pneumococcal polysaccharide and non-typeable H. influenzae protein D conjugate vaccine Rationale: The aim of this study was to demonstrate the non-inferiority of immune response to the 11Pn-PD-DiT-CRM and 12Pn-PD-DiT-CRM vaccines for at least 9 out of 11 and 10 out of 12 vaccine pneumococcal serotypes, respectively, when compared to immune responses to the licensed vaccines Synflorix TM and Prevenar 13 TM and to assess the safety of these formulations in infants. The 11-valent and 12-valent vaccines were administered as a 3-dose primary vaccination against S. pneumoniae and H. influenzae in healthy infants between 6-12 weeks (42-90 days) of age at the time of the first vaccination (Primary Phase), followed by booster vaccination at months of age (Booster Phase). Infanrix hexa vaccine was coadministered with the pneumococcal study vaccines in order to comply with the routine infant immunisation program. The CTRS presents all results related to the Primary Phase (except for immunogenicity measured by opsonophacocytic activity (OPA) assay) and the safety results related to the Booster Phase. This summary will be updated when additional data become available. Synflorix (10Pn-PD-DiT): GSK Biologicals 10-valent pneumococcal polysaccharide and non-typeable H. influenzae protein D conjugate vaccine. Prevenar 13 (Prev13): Pfizer s 13-valent pneumococcal conjugate vaccine with diphtheria Cross Reactive Material 197 (CRM197) as protein carrier. Infanrix hexa (DTPa-HBV-IPV/Hib): GSK Biologicals combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and H. influenzae type b conjugate vaccine. Phase: II Study Period: 11 July to 25 April 2013 (Primary Phase, Month 3) -to 22 January 2014 (Booster Phase, Month 11) Study Design: Randomized, controlled, multi-centric study with four parallel groups (1:1:1:1). Partially-blind i.e: double-blind between 11Pn-I, 12Pn-I and 10Pn-I groups but single blind versus Prev13 group. Centres: 43 centres (13 centres in Czech Republic, 17 centres in Germany, 7 centres in Poland and 6 centres in Spain). Indication: Three-dose primary vaccination against S. pneumoniae and H. influenzae in healthy infants between 6-12 weeks (42-90 days) of age at the time of the first vaccination followed by booster vaccination at months of age. Treatment: The study groups were as follows: - 11Pn_I Group: Subjects received 3 doses of 11Pn-PD-DiT-CRM vaccine at 2, 3 and 4 months of age, during the primary vaccination phase, and a booster dose at months of age, each dose co-administered with DTPa- HBV-IPV/Hib vaccine - 12Pn_I Group: Subjects received 3 doses of 12Pn-PD-DiT-CRM vaccine at 2, 3 and 4 months of age, during the primary vaccination phase, and a booster dose at months of age, each dose co-administered with DTPa- HBV-IPV/Hib vaccine. - 10Pn_I Group: Subjects received 3 doses of 10Pn-PD-DiT vaccine at 2, 3 and 4 months of age, during the primary vaccination phase, and a booster dose at months of age, each dose co-administered with DTPa-HBV-IPV/Hib vaccine. - Prev13 Group: Subjects received 3 doses of Prev13 vaccine at 2, 3 and 4 months of age, during the primary vaccination phase, and a booster dose at months of age, each dose co-administered with DTPa-HBV-IPV/Hib vaccine. The 3 first doses of 11Pn-PD-DiT-CRM, 12Pn-PD-DiT-CRM, 10Pn-PD-DiT and Prev13 vaccines were administered intramuscularly into the right anterolateral thigh and the DTPa-HBV-IPV/Hib was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn-PD-DiT-CRM, 12Pn-PD-DiT-CRM, 10Pn-PD-DiT and Prev13 vaccines will be administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size is not adequate) and the DTPa-HBV- IPV/Hib will be administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size is not adequate).

2 Objectives: To demonstrate that GSK Biologicals 11Pn-PD-DiT-CRM vaccine co-administered with DTPa-HBV-IPV/Hib vaccine as a three-dose primary vaccination course at approximately 2, 3, 4 months of age was non-inferior for at least 9 out of 11 vaccine pneumococcal serotypes to Prev13 vaccine (for 19A) or 10Pn-PD-DiT vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of percentage of subjects with antibody concentrations 0.2 µg/ml. Criteria: Non-inferiority was demonstrated if the upper limit (UL) of the 2-sided 95.9% Confidence Interval (CI) (adjusted 1- sided alpha = 2.05%) of the difference between groups (Prev13 Group minus 11Pn Group for 19A and 10Pn Group minus 11Pn Group for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), in terms of percentage of subjects with pneumococcal antibody concentrations 0.2 µg/ml, was lower than 10% for at least 9 out of 11 vaccine pneumococcal serotypes. AND To demonstrate that GSK Biologicals 11Pn-PD-DiT-CRM vaccine co-administered with DTPa-HBV-IPV/Hib vaccine as a three-dose primary vaccination course at approximately 2, 3, 4 months of age was non-inferior for at least 9 out of 11 vaccine pneumococcal serotypes to Prev13 vaccine (for 19A) or 10Pn-PD-DiT vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of Enzyme-linked immunosorbent assay (ELISA) Geometric Mean Concentrations (GMCs). Criteria: Non-inferiority was demonstrated if the UL of the 2-sided 95.9% CI (adjusted 1-sided alpha = 2.05%) of the ELISA GMC ratios (Prev13 Group/ 11Pn Group for 19A and 10Pn Group / 11Pn Group for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), was below a limit of 2-fold for at least 9 out of 11 vaccine pneumococcal serotypes. The objectives for the 12-valent formulation were to be assessed sequentially after demonstration of the objectives for the 11- valent formulation. To demonstrate that GSK Biologicals 12Pn-PD-DiT-CRM vaccine co-administered with DTPa-HBV-IPV/Hib vaccine as a three-dose primary vaccination course at approximately 2, 3, 4 months of age was non-inferior for at least 10 out of 12 vaccine pneumococcal serotypes to Prev13 vaccine (for 6A and 19A) or 10Pn-PD-DiT vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of percentage of subjects with antibody concentrations 0.2 µg/ml. Criteria: Non-inferiority was demonstrated if the UL of the 2-sided 95.8% CI (adjusted 1-sided alpha = 2.08%) of the difference between groups (Prev13 Group minus 12Pn Group for 6A and 19A and 10Pn Group minus 12Pn Group for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), in terms of percentage of subjects with pneumococcal antibody concentrations 0.2 µg/ml, was lower than 10% for at least 10 out of 12 vaccine pneumococcal serotypes. AND To demonstrate that GSK Biologicals 12Pn-PD-DiT-CRM vaccine co-administered with DTPa-HBV-IPV/Hib as a threedose primary vaccination course at approximately 2, 3, 4 months of age was non-inferior for at least 10 out of 12 vaccine pneumococcal serotypes to Prev13 vaccine (for 6A and 19A) or 10Pn-PD-DiT vaccine (for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) in terms of ELISA GMCs. Criteria: Non-inferiority was demonstrated if the UL of the 2-sided 95.8% CI (adjusted 1-sided alpha = 2.08%) of the ELISA GMC ratios (Prev13 Group / 12Pn Group for 6A and 19A and 10Pn Group / 12Pn Group for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), was below a limit of 2-fold for at least 10 out of 12 vaccine pneumococcal serotypes. Primary Outcome/Efficacy Variable: Immunogenicity Evaluation of immune responses to components of the 11Pn-PD-DiT-CRM and/or 12Pn-PD-DiT-CRM vaccines, 1 month post-dose 3 Concentrations of antibodies against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (for 11Pn-PD-DiT-CRM and 12Pn-PD-DiT-CRM vaccines) and 6A (for 12Pn-PD-DiT-CRM vaccine). Secondary Outcome/Efficacy Variable(s): Immunogenicity Evaluation of the immune responses to components of the investigational vaccines, for additional parameters 1 month post-dose 3 and 1 month post-booster vaccination $ Concentrations of antibodies against vaccine and/or cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 6C*, 7F, 9V, 14, 18C, 19A, 19F and 23F. Opsonophagocytic activity (OPA) # against vaccine and/or cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 6C*, 7F, 9V, 14, 18C, 19A, 19F and 23F. Concentrations of antibodies against protein D (PD).

3 Evaluation of the immune responses to components of the investigational vaccines, prior to booster vaccination Concentrations of antibodies against vaccine and/or cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 6C*, 7F, 9V, 14, 18C, 19A, 19F and 23F. Concentrations of antibodies against PD. Safety Occurrence of each solicited adverse event (AE), within 4 days (Days 0-3) after each vaccine dose. Solicited local AEs (any, grade 3). Solicited general AEs (any, grade 3, related). Occurrence of unsolicited AEs within 31 days (Days 0-30) after each vaccination. Occurrence of serious adverse events (SAEs) during the entire study period (from Month 0 up to Month 11) *Testing for pneumococcal serotype 6C will be performed if specific qualified assay will be available and this summary will be updated accordingly. # OPA results were not available at the time of writing this summary. The CTRS will be updated when they become available. $ The immunogenicity results of the booster vaccination phase were not available at the time of writing this summary. The CTRS will be updated when they become available. Statistical Methods: The analyses were performed on the Total Vaccinated cohort for the Primary Phase, the According-to-Protocol (ATP) cohort for immunogenicity for the Primary Phase and the Total Vaccinated cohort for the Booster Phase. The Total Vaccinated cohort for the Primary Phase included all subjects who received at least one dose of the primary vaccination. The ATP cohort for immunogenicity for the Primary Phase included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals relative to the Primary Phase defined in the protocol, with no elimination criteria during the Primary Phase of the study) for whom data concerning primary immunogenicity outcome measures were available and for whom assay results were available for antibodies against at least one vaccine antigen component after primary vaccination. The Total Vaccinated cohort for the Booster Phase included all subjects who received the booster dose of study vaccine. Analysis of Immunogenicity: The analysis was performed on the ATP cohort for immunogenicity of the Primary Phase. For the first sequential objective related to 11Pn-PD-DiT-CRM vaccine, 95.9% CIs (adjusted 1-sided alpha = 2.05%) around the difference between groups (Prev13 group minus 11Pn_I group for 19A or 10Pn_I group minus 11Pn_I group for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F serotypes), in percentage of subjects with pneumococcal antibody concentrations 0.2 µg/ml, 1 month after the 3-dose primary vaccination, was computed for each of the 11 vaccine pneumococcal serotypes. Also, 95.9% CIs (adjusted 1-sided alpha = 2.05%) around the ELISA GMCs ratio between groups (Prev13/11Pn_I for 19A and 10Pn_I/11Pn_I for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), 1 month after the 3-dose primary vaccination, was computed for each of the 11 vaccine pneumococcal serotypes. The first sequential objective would be reached: if the UL of the 2-sided 95.9% CI around the difference between groups would be lower than 10% for at least 9 out of 11 vaccine pneumococcal serotypes AND if the UL of the 2-sided 95.9% CI around ELISA GMCs ratio between groups would be below a limit of 2-fold for at least 9 out of 11 vaccine pneumococcal serotypes. For the second sequential objective related to 12Pn-PD-DiT-CRM vaccine, 95.8% CIs (adjusted 1-sided alpha = 2.08%) around the difference between groups (Prev13 group minus 12Pn_I group for 6A and 19A or 10Pn_I group minus 12Pn_I group for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F serotypes), in percentage of subjects with pneumococcal antibody concentrations 0.2 µg/ml, 1 month after the 3-dose primary vaccination, was computed for each of the 12 vaccine pneumococcal serotypes. Also, 95.8% CIs (adjusted 1-sided alpha = 2.08%) around the ELISA GMCs ratio between groups (Prev13/12Pn_I for 6A and 19A and 10Pn_I/12Pn_I for 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), after the 3-dose primary vaccination, was computed for each of the 12 vaccine pneumococcal serotypes. The second sequential objective would be reached: if the first sequential objective would be reached AND

4 AND if the UL of the 2-sided 95.8% CI of the difference between groups would be lower than 10% for at least 10 out of 12 vaccine pneumococcal serotypes if the UL of the 2-sided 95.8% CI around ELISA GMCs ratio between groups would be below a limit of 2-fold for at least 10 out of 12 vaccine pneumococcal serotypes. Seropositivity rates* and GMCs with 95% CIs for anti-1, anti-3, anti-4, anti-5, anti-6a, anti-6b, anti-7f, anti-9v, anti-14, anti- 18C, anti-19a, anti-19f and anti-23f measured by ELISA were tabulated for each group, prior to & 1 month after the 3-dose primary vaccination. Seropositivity rates* and GMCs with 95% CIs for anti-pd antibodies measured by ELISA were also tabulated for each group. *A seropositive subject was defined as a subject with concentration/titre the predefined cut-off value specific to the antigen/antibody under consideration: For serotype-specific anti-pneumococcal antibody concentrations: 0.05 µg/ml For anti-pd antibody concentrations: 100 EU/mL, Analysis of Safety The analysis was performed on the Total Vaccinated cohort for the Primary Phase and the Total Vaccinated cohort for the Booster Phase. For each group, the percentage of subjects with each individual solicited local and general symptom during the 4-day (Days 0-3) follow-up period was tabulated with exact 95% CI for each vaccine dose and across primary doses. The same tabulation was performed for Grade 3 solicited symptoms and general solicited symptoms assessed by the investigator as causally related to the vaccination. The percentage of subjects with at least 1 unsolicited AE within the 31-Day (Days 0-30) postprimary vaccination and post-booster vaccination follow-up periods was tabulated per group according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. SAEs occurring from study start up to Month 3 and during the whole study period were also tabulated according to MedDRA preferred term. Study Population: Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, born after a gestation period of at least 36 weeks, without previous vaccination against S. pneumonia, diphtheria, tetanus, pertussis, polio or H. influenzae type b, were included in the study. Written informed consent was obtained from the parent(s) or legally acceptable representative(s) of the subjects before study entry. Primary Phase Number of Subjects: 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group Planned, N Randomized, N (Total Vaccinated cohort for Primary Phase) Completed, n (%) 238 (99.2) 228 (95.0) 226 (98.3) 235 (97.5) Total Number Subjects Withdrawn, n (%) 2 (0.8) 12 (5.0) 4 (1.7) 6 (2.5) Withdrawn due to Adverse Events, n (%) 0 (0.0) 1 (0.4) 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 (%) 2 (0.8) 11 (4.6) 4 (1.7) 6 (2.5) Demographics 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group N (Total Vaccinated cohort for Primary Phase) Sex, n (%) Females 113 (47.1) 120 (50.0) 113 (49.1) 121 (50.2) Males 127 (52.9) 120 (50.0) 117 (50.9) 120 (49.8) Mean Age, weeks (SD) 8.6 (1.49) 8.7 (1.61) 8.7 (1.62) 8.6 (1.54) Median Minimum, Maximum 6, 12 6, 13 6, 13 6, 12 White - Caucasian/European heritage, n (%) 235 (97.9) 235 (97.9) 228 (99.1) 235 (97.5) Booster Phase Number of Subjects: 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group Planned, N Randomized, N (Total Vaccinated cohort for Booster Phase) Completed, n (%) 236 (99.5) 223 (98.7) 220 (99.1) 233 (99.6) Total Number Subjects Withdrawn, n (%) 1 (0.5) 3 (1.3) 2 (0.9) 1 (0.4)

5 Withdrawn due to Adverse Events, n (%) 0 (0.0) 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 (0.5) 3 (1.3) 2 (0.9) 1 (0.4) Demographics 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group N (Total Vaccinated cohort for Booster Phase) Sex, n (%) Females 111 (46.8) 113 (50.0) 107 (48.2) 116 (49.6) Males 126 (53.2) 113 (50.0) 115 (51.8) 118 (50.4) Mean Age, months (SD) 12.3 (0.58) 12.3 (0.58) 12.4 (0.61) 12.3 (0.63) Median Minimum, Maximum 12, 14 12, 14 11, 14 11, 15 White - Caucasian/European heritage, n (%) 232 (97.9) 221 (97.8) 220 (99.1) 228 (97.4) Primary Efficacy Results: Difference between groups (10Pn_I minus 11Pn_I) in percentage of subjects with antibody concentrations 0.2 µg/ml, 1 month post-dose 3, for pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Difference in percentage (10Pn_I Group minus 11Pn_I Group) Antibody 10Pn_I Group 11Pn_I Group % 95.9 % CI N % N % LL UL* ANTI ANTI ANTI ANTI-6B ANTI-7F ANTI-9V ANTI ANTI-18C ANTI-19F ANTI-23F N = number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations 0.2 µg/ml 95.9 % CI = Standardized asymptotic 95.9 % confidence interval, LL = Lower Limit, UL = Upper Limit *Criterion for Non-inferiority: UL of the 2-sided 95.9% CI of the difference between (Prev13 group minus 11Pn_I group) and (10Pn_I group minus 11Pn_I group) < 10% for at least 9 out of 11 vaccine pneumococcal serotypes. Primary Efficacy Results: Ratios of GMCs, 1 month post-dose 3, between groups (10Pn_I over 11Pn_I) for ANTI-1, ANTI- 4, ANTI-5, ANTI-6B, ANTI-7F, ANTI-9V, ANTI-14, ANTI-18C, ANTI-19F and ANTI-23F antibody concentrations (22Finhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Adjusted GMC ratio (10Pn_I Group / 11Pn_I Group) Antibody 10Pn_I Group 11Pn_I Group Value 95.9% CI N Adjusted GMC N Adjusted GMC LL UL* ANTI ANTI ANTI ANTI-6B ANTI-7F ANTI-9V ANTI ANTI-18C ANTI-19F ANTI-23F Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = number of subjects with both pre- and post-vaccination results available 95.9% CI = 95.9% confidence interval for the adjusted GMC ratio; LL = lower limit, UL = upper limit *Criterion for Non-inferiority: UL of the 2-sided 95.9% CI of the adjusted antibody GMC ratios of (Prev13 group/11pn_i group)

6 and (10Pn_I group/11pn_i group) < 2 for at least 9 out of 11 vaccine pneumococcal serotypes. Primary Efficacy Results: Difference between groups (Prev13 minus 11Pn_I), in percentage of subjects with antibody concentrations 0.2 µg/ml, 1 month post-dose 3, for pneumococcal serotypes 19A (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Difference in percentage (Prev13 Group minus 11Pn_I Group) Antibody Prev13 Group 11Pn_I Group % 95.9 % CI N % N % LL UL* ANTI-19A N = Number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations 0.2 µg/ml 95.9 % CI = Standardized asymptotic 95.9 % confidence interval, LL = Lower Limit, UL = Upper Limit *Criterion for Non-inferiority: UL of the 2-sided 95.9% CI of the difference between (Prev13 group minus 11Pn_I group) and (10Pn_I group minus 11Pn_I group) < 10% for at least 9 out of 11 vaccine pneumococcal serotypes Primary Efficacy Results: Ratios of GMCs, 1 month post-dose 3, between groups (Prev13 over 11Pn_I) for ANTI-19A antibody concentrations (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Adjusted GMC ratio (Prev13 Group / 11Pn_I Group) Antibody Prev13 Group 11Pn_I Group Value 95.9% CI N Adjusted GMC N Adjusted GMC LL UL* ANTI-19A Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = Number of subjects with both pre- and post-vaccination results available 95.9% CI = 95.9% confidence interval for the adjusted GMC ratio; LL = lower limit, UL = upper limit *Criterion for Non-inferiority: UL of the 2-sided 95.9% CI of the adjusted antibody GMC ratio of (Prev13 group/11pn_i group) and (10Pn_I group/11pn_i group) < 2 for at least 9 out of 11 vaccine pneumococcal serotypes. Primary Efficacy Results: Difference between groups (10Pn_I minus 12Pn_I), in percentage of subjects with antibody concentrations 0.2 µg/ml, 1 month post-dose 3, for pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Difference in percentage (10Pn_I Group minus 12Pn_I Group) Antibody 10Pn_I Group 12Pn_I Group % 95.8 % CI N % N % LL UL ANTI ANTI ANTI ANTI-6B ANTI-7F ANTI-9V ANTI ANTI-18C ANTI-19F ANTI-23F N = Number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations 0.2 µg/ml 95.8 % CI = Standardized asymptotic 95.8 % confidence interval, LL = Lower Limit, UL = Upper Limit *Criterion for Non-inferiority: UL of the 2-sided 95.8% CI of the difference between (Prev13 group minus 12Pn_I group) and (10Pn_I group minus 12Pn_I group) < 10% for at least 10 out of 12 vaccine pneumococcal serotypes. Primary Efficacy Results: Ratios of GMCs, 1 month post-dose 3, between groups (10Pn_I over 12Pn_I) for ANTI-1, ANTI- 4, ANTI-5, ANTI-6B, ANTI-7F, ANTI-9V, ANTI-14, ANTI-18C, ANTI-19F and ANTI-23F antibody concentrations (22Finhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Adjusted GMC ratio (10Pn_I Group / 12Pn_I Group) Antibody 10Pn_I Group 12Pn_I Group Value 95.8% CI N Adjusted GMC N Adjusted GMC LL UL*

7 ANTI ANTI ANTI ANTI-6B ANTI-7F ANTI-9V ANTI ANTI-18C ANTI-19F ANTI-23F Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = Number of subjects with both pre- and post-vaccination results available 95.8% CI = 95.8% confidence interval for the adjusted GMC ratio; LL = lower limit, UL = upper limit *Criterion for Non-inferiority: UL of the 2-sided 95.8% CI of the adjusted antibody GMC ratios of (Prev13 group/12pn_i group) and (10Pn_I group/12pn_i group) < 2 for at least 10 out of 12 vaccine pneumococcal serotypes. Primary Efficacy Results: Difference between groups (Prev13 minus 12Pn_I) in percentage of subjects with antibody concentrations 0.2 µg/ml,1 month post-dose 3, for pneumococcal serotypes 6A and 19A (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Difference in percentage (Prev13 Group minus 12Pn_I Group) Antibody Prev13 Group 12Pn_I Group % 95.8 % CI N % N % LL UL* ANTI-6A ANTI-19A N = Number of subjects with post primary vaccination results available % = percentage of subjects with ELISA pneumococcal antibody concentrations 0.2 µg/ml 95.8 % CI = Standardized asymptotic 95.8 % confidence interval, LL = Lower Limit, UL = Upper Limit *Criterion for Non-inferiority: UL of the 2-sided 95.8% CI of the difference between (Prev13 group minus 12Pn_I group) and (10Pn_I group minus 12Pn_I group) < 10% for at least 10 out of 12 vaccine pneumococcal serotypes. Primary Efficacy Results: Ratios of GMCs, 1 month post-dose 3, between groups (Prev13 over 12Pn_I), for ANTI-6A and ANTI-19A antibody concentrations (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) Adjusted GMC ratio (Prev13 Group / 12Pn_I Group) Antibody Prev13 Group 12Pn_I Group Value 95.8% CI N Adjusted GMC N Adjusted GMC LL UL* ANTI-6A ANTI-19A Adjusted GMC = geometric mean antibody concentration adjusted for baseline concentration N = Number of subjects with both pre- and post-vaccination results available 95.8% CI = 95.8% confidence interval for the adjusted GMC ratio; LL = lower limit, UL = upper limit *Criterion for Non-inferiority: UL of the 2-sided 95.8% CI of the adjusted antibody GMC ratios of (Prev13 group/12pn_i group) and (10Pn_I group/12pn_i group) < 2 for at least 10 out of 12 vaccine pneumococcal serotypes. Primary Efficacy Results: Seropositivity rates and GMCs for ANTI-1, ANTI-4, ANTI-5, ANTI-6A, ANTI-6B, ANTI-7F, ANTI-9V, ANTI-14, ANTI-18C, ANTI-19A, ANTI-19F and ANTI-23F antibodies (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) 0.05 µg/ml 0.2 µg/ml GMC (µg/ml) 95% CI 95% CI 95% CI Antibody Group Timing N n % LL UL n % LL UL value LL UL ANTI-1 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE

8 PIII(M3) ANTI-4 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-5 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-6A 11Pn_I PRE PIII(M3) Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-6B 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-7F 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-9V 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-14 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)

9 Prev13 PRE PIII(M3) ANTI-18C 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-19A 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-19F 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) ANTI-23F 11Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3)* Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) Seropositivity rate = serotype-specific anti-pneumococcal antibody concentration 0.05 µg/ml GMC = geometric mean concentration N = number of subjects with available results n/% = number/percentage of subjects with concentration within the specified range 95% CI = 95% confidence interval: LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination PIII(M3) = One month after dose 3 *Primary outcome variable Secondary Outcome Results: Seropositivity rates and GMCs for ANTI-3 antibodies (22F-inhibition ELISA) (ATP cohort for immunogenicity of the Primary Phase) 0.05 µg/ml 0.2 µg/ml GMC (µg/ml) 95% CI 95% CI 95% CI Antibody Group Timing N n % LL UL n % LL UL value LL UL ANTI-3 11Pn_I PRE PIII(M3) Pn_I PRE PIII(M3) Pn_I PRE PIII(M3) Prev13 PRE PIII(M3)

10 Seropositivity rate = Anti-pneumococcal serotype 3 antibody concentration 0.05 µg/ml GMC = geometric mean concentration N = number of subjects with available results n/% = number/percentage of subjects with concentration within the specified range 95% CI = 95% confidence interval: LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination PIII(M3) = One month after dose 3 Secondary Outcome Results: Seropositivity rates and GMCs for ANTI-PD antibodies (ATP cohort for immunogenicity of the Primary Phase) 100 EU/mL GMC(EU/mL) 95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL ANTI-PD 11Pn_I PRE PIII(M3) Pn_I PRE PIII(M3) Pn_I PRE PIII(M3) Prev13 PRE PIII(M3) Seropositivity rate = anti-pd antibody concentration 100 EU/mL GMC = geometric mean concentration N = number of subjects with available results n/% = number/percentage of subjects with concentration within the specified range 95% CI = 95% confidence interval: LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination PIII(M3) = One month after dose 3 Secondary Outcome Results: Number (%) of subjects reporting solicited local symptoms during the 4-day (Days 0-3) postvaccination period following each primary dose and across doses (Total Vaccinated cohort for the Primary Phase) 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group 95 % CI 95 % CI 95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL N n % LL UL N n % LL UL Dose 1 Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Dose 2 Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Dose 3 Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Across Doses

11 Pain Any Grade Redness Any >30 mm Swelling Any >30 mm N= number of subjects with at least one documented dose n/%= number/percentage of subjects reporting the symptom at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of the local symptom specified regardless of intensity grade Grade 3 pain = cried when limb was moved/spontaneously painful Secondary Outcome Results: Number (%) of subjects reporting solicited local symptoms during the 4-day (Days 0-3) postvaccination period following the booster dose (Total Vaccinated cohort for the Booster Phase) Symptom Intensity 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group 95% 95% 95% 95% N n % LL UL N n % LL UL N n % LL UL N n % LL UL Pain Any Grade Redness Any >30 mm Swelling Any >30 mm N= number of subjects with the documented dose n/%= number/percentage of subjects reporting the symptom at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of the local symptom specified regardless of intensity grade Grade 3 pain = cried when limb was moved/spontaneously painful Secondary Outcome Results: Number (%) of subjects reporting solicited general symptoms during the 4-day (Days 0-3) postvaccination period following each primary dose and across doses (Total Vaccinated cohort for the Primary Phase) 11Pn_I Group 12Pn_I Group Symptom Intensity/R elationship 95 % CI 95 % CI N n % LL UL N n % LL UL Dose 1 Drowsiness Any Grade Related Irritability / fussiness Loss of appetite Fever Any Grade Related Any Grade Related C > 40.0 C Related Dose 2 Drowsiness Any Grade Related Irritability / Any fussiness Grade Related Loss of Any

12 appetite Grade Related Fever 38.0 C > 40.0 C Related Dose 3 Drowsiness Any Grade Related Irritability / fussiness Loss of appetite Fever Any Grade Related All Grade Related C > 40.0 C Related Across Doses Drowsiness Any Grade Related Irritability / fussiness Loss of appetite Fever Symptom Any Grade Related Any Grade Related C > 40.0 C Related Intensity/Relat ionship 10Pn_I Group Prev13 Group 95 % CI 95 % CI N n % LL UL N n % LL UL Dose 1 Drowsiness Any Grade Related Irritability / fussiness Loss of appetite Fever Any Grade Related Any Grade Related C > 40.0 C Related Dose 2 Drowsiness Any Grade Related Irritability / Any

13 fussiness Grade Related Loss of Any appetite Grade Fever Related C > 40.0 C Related Dose 3 Drowsiness Any Grade Related Irritability / fussiness Loss of appetite Fever Any Grade Related Any Grade Related C > 40.0 C Related Across Doses Drowsiness Any Grade Related Irritability / fussiness Loss of appetite Fever Any Grade Related Any Grade Related C > 40.0 C Related N= number of subjects with at least one documented dose n/%= number/percentage of subjects reporting the symptom at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = Any reported symptom, regardless of intensity or relationship to vaccination Grade 3 Irritability/Fussiness: Crying that could not be comforted, prevented normal activity Grade 3 Drowsiness = Symptom that prevented normal activity Grade 3 Loss of appetite = Not eating at all Related = general symptom assessed by the investigator as causally related to the study vaccination Secondary Outcome Results: Number (%) of subjects reporting solicited general symptoms during the 4-day (Days 0-3) postvaccination period following the booster dose (Total Vaccinated cohort for the Booster Phase) Symptom Intensity /Relation ship Drowsiness 11Pn_I Group 12Pn_I Group 10Pn_I Group Prev13 Group 95% 95% 95% 95% N n % LL UL N n % LL UL N n % LL UL N n % LL UL Any Grade Related Irritability Any Grade Related Loss of appetite Any Grade

14 Fever Related C > 40.0 C Related N= number of subjects with the documented dose n/%= number/percentage of subjects reporting the symptom at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = Any reported symptom, regardless of intensity or relationship to vaccination Grade 3 Irritability/Fussiness: Crying that could not be comforted, prevented normal activity Grade 3 Drowsiness = Symptom that prevented normal activity Grade 3 Loss of appetite = Not eating at all Related = general symptom assessed by the investigator as causally related to the study vaccination Safety Results: Number(%) of subjects reporting the occurrence of unsolicited AEs within the 31-day (Days 0-30) post-primary vaccination period (Total Vaccinated cohort for the Primary Phase) Most frequent adverse events - On-Therapy (occurring within Days 0-30 following vaccination) 11Pn_I Group N = Pn_I Group N = Pn_I Group N = 230 Prev13 Group N = 241 Subjects with any AE(s), n (%) 110 (45.8) 108 (45.0) 123 (53.5) 124 (51.5) Upper respiratory tract infection 38 (15.8) 39 (16.3) 49 (21.3) 28 (11.6) Rhinitis 18 (7.5) 15 (6.3) 12 (5.2) 16 (6.6) Bronchiolitis 12 (5.0) 10 (4.2) 13 (5.7) 11 (4.6) Bronchitis 10 (4.2) - 18 (7.8) 16 (6.6) Nasopharyngitis 10 (4.2) 14 (5.8) 8 (3.5) 11 (4.6) Conjunctivitis 10 (4.2) - 8 (3.5) - Pyrexia - 10 (4.2) - - Diarrhoea (3.5) - Counting rule applied: As there were more than 30 subjects per treatment group and > 3 groups, only the 5 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 5 most frequent events for that group. Safety Results: Number(%) of subjects reporting the occurrence of unsolicited AEs within the 31-day (Days 0-30) post-booster vaccination period (Total Vaccinated cohort for the Booster Phase) Most frequent adverse events - On-Therapy (occurring within Days 0-30 following vaccination) 11Pn_I Group N = Pn_I Group N = Pn_I Group N = 222 Prev13 Group N = 234 Subjects with any AE(s), n (%) 69 (29.1) 68 (30.1) 74 (33.3) 53 (22.6) Upper respiratory tract infection 11 (4.6) 16 (7.1) 20 (9.0) 13 (5.6) Bronchitis - 6 (2.7) 10 (4.5) 5 (2.1) Gastroenteritis 10 (4.2) - 5 (2.3) - Nasopharyngitis 7 (3.0) 7 (3.1) - - Pyrexia - 5 (2.2) - 6 (2.6) Vomiting 6 (2.5) - 4 (1.8) - Diarrhoea (2.3) 3 (1.3) Tonsillitis - 5 (2.2) - 3 (1.3) Rhinitis - 6 (2.7) - - Laryngitis - 5 (2.2) - - Viral infection 5 (2.1) Pharyngitis (1.7) Impetigo (1.3) Otitis media (1.3) Rash (1.3) Counting rule applied: As there were more than 30 subjects per treatment group and > 3 groups, only the 5 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 5 most frequent events for that group. Safety Results: Number(%) of subjects with SAEs during the Primary Phase from Month 0 up to Month 3 (Total Vaccinated cohort for the Primary Phase)