Study No.: Title: Rationale: Phase: Study Period: Study Design: Centers: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:

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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. Study No.: (10PN-PD-DIT-018 BST: 012) Title: Booster vaccination course with the pneumococcal vaccine GSK A, DTPw-HBV/Hib and OPV or IPV in children who completed the primary vaccination course 10PN-PD-DIT-012 (107007). 10Pn-PD-DiT vaccine (10Pn): GlaxoSmithKline (GSK) Biologicals 10-valent pneumococcal conjugate vaccine Tritanrix -HepB/Hib (DTPw-HBV/Hib): GSK Biologicals diphtheria-tetanus-whole cell pertussis-hepatitis B vaccine extemporaneously mixed with a lyophilized Haemophilus influenzae type b tetanus conjugate vaccine component. Poliorix (IPV): GSK Biologicals inactivated polio vaccine. Polio Sabin (OPV): GSK Biologicals oral polio vaccine. Rationale: To evaluate the safety following a fourth dose of 10Pn-PD-DiT vaccine or Prevenar TM co-administered with DTPw-HBV/Hib and OPV or IPV vaccines. The booster immune response by giving a booster dose of 10Pn-PD-DiT vaccine or Prevenar TM co-administered with DTPw-HBV/Hib and OPV or IPV vaccines at months of age following a 3-dose primary vaccination course according to 2 different primary vaccination schedules was evaluated. The persistence of antibodies induced following primary vaccinations with 10Pn-PD-DiT vaccine or Prevenar TM was also assessed. Prevenar TM (7Pn): Wyeth s 7-valent pneumococcal conjugate vaccine. This CTRS presents the results for the booster phase only. Please refer to 10PN-PD-DIT-012 (107007) CTRS for results of the primary study. Phase: III Study Period: 22 October 2007 to 07 October 2008 (including the safety follow-up) Study Design: Multicenter, multi-country, double-blind, controlled study with 2 parallel groups (3:1) Centers: 7 centers, 1 in the Philippines and 6 in Poland. Indication: Booster vaccination against Streptococcus pneumoniae, diphtheria, tetanus, pertussis, Hib, hepatitis B and polio Treatment: All subjects received the same study vaccines as in the primary vaccination study 10PN-PD-DIT-012 (107007). The study groups were as follows: 10Pn : received the 10Pn-PD-DiT vaccine, either co-administered with DTPw-HBV/Hib and OPV (10PnEPI ) in the Philippines, or co-administered with DTPw-HBV/Hib and IPV (10Pn246 ) in Poland. 7Pn received the 7Pn vaccine, co-administered either with DTPw-HBV/Hib and OPV (7PnEPI ) in the Philippines or with DTPw-HBV/Hib and IPV vaccines (7Pn246 ) in Poland. Vaccines were administered at months of age by intramuscular injection except OPV that was administered orally; 10Pn and 7Pn were injected in the right thigh or deltoid, DTPw-HBV/Hib in the upper left thigh or deltoid and IPV in the lower left thigh or deltoid. Objectives: To demonstrate that a booster dose of 10Pn vaccine is non-inferior to 7Pn when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines, in terms of post-immunization booster reactions with rectal temperature > 39.0 C in children at 12 to 18 months of age. Criterion for safety: Demonstration of non-inferiority refers to the statistical method used to rule out an increase in the incidence of postimmunization febrile reactions with rectal temperature > 39.0 C in the 10Pn-PD-DiT vaccine group compared to the control group (10Pn as compared to 7Pn) for the pooled groups, that would exceed a pre-defined limit of 5% + half the incidence in the control group considered to be clinically acceptable. Primary Outcome/Efficacy Variable: Occurrence of fever with rectal temperature > 39 C within 4 days (Day 0 to Day 3) after the booster vaccination. Secondary Outcome/Efficacy Variables: Safety: Occurrence of solicited local symptoms (any and Grade 3) within 4 days (Day 0 to Day 3) after booster vaccination. Occurrence of solicited general symptoms (any and Grade 3) within 4 days (Day 0 to Day 3) after booster vaccination. Occurrence of unsolicited adverse events (AEs) within 31 days (Day 0 to Day 30) after booster vaccination. Occurrence of serious adverse events (SAEs) throughout the active phase of the study (from the beginning of the booster phase up to 1 month after the booster dose). Occurrence of SAEs throughout the entire study period starting from the beginning of the booster phase up to the end of the extended 6-month safety follow-up (ESFU). 1

2 Immunogenicity: Prior to and one month after the booster vaccination with 10Pn or 7Pn, co-administered with DTPw-HBV/Hib + OPV or IPV vaccines (pneumo subset: 2 independent subsets of subjects in a 3:1 ratio were prepared for the serological testing): Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F antibody concentrations 0.20 µg/ml. Antibody concentrations to pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Antibody concentrations to protein D (PD). Antibody concentrations against pneumococcal cross-reactive serotypes 6A and 19A. Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A. 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-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations 0.05 µg/ml. Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A 8. Anti-PD antibody concentrations 100 EL.U/mL. Prior to and one month after the administration of the booster dose of DTPw-HBV/Hib + OPV or IPV (co-administration subsets 1 and 2, subjects not included in the pneumo subset): Anti-diphtheria (DT) and anti-tetanus toxoids (TT), anti-polyribosyl-ribitol phosphate (PRP), anti-bordetella pertussis (BPT), anti-hepatitis B surface antigen (HBs) antibody concentrations, and anti-polio type 1, 2 and 3 titers. Seropositivity status, defined as: Anti-BPT antibody concentrations 15 EL.U/mL. Seroprotection status, defined as: Anti-DT antibody concentrations 0.1 IU/mL by ELISA Anti-TT antibody concentrations 0.1 IU/mL. Anti-PRP antibody concentrations 0.15 µg/ml and 1.0 µg/ml Anti-HBs antibody concentrations 10 miu/ml. Anti-polio type 1 titers 8. Anti-polio type 2 titers 8. Anti-polio type 3 titers 8. Booster immune response to BPT, one month after the booster dose, defined as the appearance of antibodies (i.e. concentrations 15 EL.U/mL) in subjects seronegative at pre-vaccination (i.e. with concentrations < 15 EL.U/mL), or at least 2-fold increase of pre-vaccination antibody concentrations in those who were initially seropositive at prevaccination (i.e. with concentrations 15 EL.U/mL). Statistical Methods: The analyses were performed on the Total Vaccinated Cohort, the According-To-Protocol (ATP) cohort for immunogenicity and the ATP cohort for persistence. The Total Vaccinated cohort included all vaccinated subjects The ATP cohort for persistence included all subjects 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 (pre-booster blood sampling). 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 immunogenicity data were available. This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. Analysis of Safety The analysis was performed on the Total Vaccinated Cohort. Inferential analysis: Standardized asymptotic 95% confidence interval (CIs) for the difference between groups (10Pn minus 7Pn ), in percentage of subjects reporting fever > 39.0 C (rectal temperature) after the booster vaccination. The one-sided P-value for the null hypothesis that the increase in the percentage of subjects with rectal temperature > 39.0 C (10Pn as compared 7Pn ) was above 5% + half the incidence in the control group. 2

3 Descriptive analysis: The percentage of subjects with fever > 39.0 C (rectal temperature), within 4 days (Day 0 to 3) after booster vaccination, was tabulated with exact 95%CIs. The percentage of subjects reporting each individual solicited local and general symptom during the solicited follow-up period of 4 days (days 0 to 3) after the booster dose was tabulated, with exact 95% CI. The same tabulation was performed for grade 3 AEs and for general AEs with relationship to vaccination. The proportion of subjects reporting at least one unsolicited AEs classified by the Medical Dictionary for Regulatory Activities (MedDRA) preferred term occurring up to 30 days after booster vaccination was tabulated. Occurrences of SAEs throughout the entire study period starting from the beginning of the booster phase up to the end of the ESFU were tabulated according to MedDRA preferred term. Analysis of Immunogenicity: The analyses were performed on the ATP cohort for immunogenicity and ATP cohort for persistence. For each treatment group, at each time point that a blood sample result was available, the geometric mean antibody concentrations/titers (GMCs/GMTs) with 95% CI and Seropositivity/seroprotection/booster immune response rates with exact 95% CIs were calculated for each serotype/antigen. Study Population: Male or female subjects between, and including, months of age at the time of the booster vaccination, whose parents/guardians the investigator believed could and would comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). Subjects previously participated in study 10PN-PD- DIT-012 (107007) and received 3 doses of pneumococcal conjugate vaccine and were 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 prior to study entry. Active Phase Number of subjects 10PnEPI 7PnEPI 10Pn246 7Pn246 Planned, N Entered, N (Total Vaccinated Cohort) Completed, n (%)* 280 (100) 93 (100) 275 (96.5) 96 (98.0) Total Number Subjects Withdrawn, n (%) 0 (0.0) 0 (0.0) 10 (3.5) 2 (2.0) Withdrawn due to AE, 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 (%) 0 (0.0) 0 (0.0) 10 (3.5) 2 (2.0) Demographics 10PnEPI 7PnEPI 10Pn246 7Pn246 N (Total Vaccinated Cohort) Females:Males 133:147 43:50 134:151 43:55 Mean Age, months (SD) 16.2 (0.66) 16.2 (0.59) 17.2 (0.84) 17.2 (0.88) White - Caucasian / European heritage, n (%) (100) 98 (100) Asian south east Asian heritage 280 (100) 93 (100) - - Extended safety follow-up Number of subjects 10PnEPI 7PnEPI 10Pn246 7Pn Subjects in Total Vaccinated Cohort (active phase), N) Subjects in ESFU cohort, n (%) Subjects not contacted for ESFU phase, n (%) 0 (0.0) 0 (0.0) 13 (4.8) 3 (3.2) Not contacted due to consent withdrawal, n (%) 0 (0.0) 0 (0.0) 2 (0.7) 0 Not contacted due to lost to follow up, n (%) 0 (0.0) 0 (0.0) 11 (4.0) 3 (3.2) Demographics 10PnEPI 7PnEPI 10Pn246 7Pn246 N (ESFU cohort) Females:Males 133:147 43:50 129:143 42:53 Mean Age, months (SD) 22.4 (0.81) 22.3 (0.84) 23.5 (0.87) 23.5 (0.86) White - Caucasian / European heritage, n (%) (100) 95 (100) Asian - south east Asian heritage, n (%) 280 (100) 93 (100) - - Primary Efficacy Results: Difference between groups (10Pn minus 7Pn) in terms of percentage of subjects reporting fever 3

4 with rectal temperature > 39 C during the 4-day (Day 0 to Day 3) post-vaccination period (Total Vaccinated cohort) Difference in percentage (10Pn minus 7Pn) 10Pn 7Pn 95% CI Symptoms Type N n % N n % % LL UL P-value Fever/(Rectally) ( C) > 39.0 C <0.001 N = Number of subjects with the documented dose n/% = number/percentage of subjects reporting a specified symptom 95% CI = Standardized asymptotic 95% confidence interval, LL = Lower Limit, UL = Upper Limit. Secondary Outcome Variables: Incidence of solicited local symptoms reported during the 4-day (Days 0-3) postvaccination period, per schedule (Total vaccinated cohort) 10PnEPI 7PnEPI 10Pn246 7Pn % CI 95 % CI 95 % CI 95 % CI Symptom Type 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 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 Grade 3 Pain = cried when limb was moved/spontaneously painful Secondary Outcome Variables: Incidence of solicited general symptoms reported during the 4-day (Days 0-3) postvaccination period, per schedule (Total vaccinated cohort) 10PnEPI 7PnEPI 10Pn246 7Pn % CI 95 % CI 95 % CI 95 % CI Symptom Type N n % LL UL N n % LL UL N n % LL UL N n % LL UL Drowsiness Any Grade Related Fever (Rectally) 38 C >39 C >40 C Related Irritability Any Grade Related Loss of appetite Any Grade Related N= number of subjects with the 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 general symptom irrespective of intensity grade or relationship to vaccination Grade 3 Drowsiness = drowsiness that prevented normal everyday activities Grade 3 Irritability = crying that could not be comforted/prevented normal everyday activities Grade 3 Loss of appetite = not eating at all Related = symptom considered by the investigator to have a causal relationship to study vaccination Secondary Outcome Variables: 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 antibodies (22F-inhibition ELISA), per schedule (ATP cohort for persistence) 0.05 g/ml 0.20 g/ml GMC 4

5 95% CI Antibody Timing N n % LL UL n % LL UL value LL UL Anti-1 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-4 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-5 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-6B 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-7F 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-9V 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-14 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster

6 10Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-18C 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-19F 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-23F 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: Seropositivity rates and GMCs for ANTI-6A and ANTI-19A antibodies (22F-inhibition ELISA), per schedule (ATP cohort for persistence) 0.05 g/ml 0.20 g/ml GMC 95% CI Antibody Timing N n % LL UL n % LL UL value LL UL Anti-6A 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti-19A 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster

7 7Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: 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, per schedule (ATP cohort for persistence) 8 GMT Antibody Timing N n % LL UL value LL UL Opsono-1 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-4 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-5 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-6B 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-7F 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5)

8 Pre-booster Opsono-9V 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-14 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-18C 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-19F 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-23F 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster GMT = geometric mean titer n/%= number/percentage of subjects with titer within the specified range Secondary Outcome Variables: Seropositivity rates and GMTs for OPSONO-6A and OPSONO-19A, per schedule (ATP cohort for persistence) 8 GMT Antibody Timing N n % LL UL value LL UL Opsono-6A 10PnEPI PIII(M3)

9 Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Opsono-19A 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster GMT = geometric mean titer n/%= number/percentage of subjects with titer within the specified range Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-PD antibodies, per schedule (ATP cohort for persistence) 100 EL.U/mL GMC Antibody Timing N n % LL UL value LL UL Anti-PD 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-DT and Anti-TT antibodies, per schedule (ATP cohort for persistence) 0.1 IU/mL GMC Antibody Timing N n % LL UL value LL UL Anti-DT 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster

10 Anti-TT 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-BPT antibodies, per schedule (ATP cohort for persistence) 15 EL.U/mL GMC Antibody Timing N n % LL UL value LL UL Anti-BPT 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: Seroprotection rates and GMCs for Anti-HBs antibodies (ATP cohort for persistence) 10 miu/ml GMC Antibody Timing N n % LL UL value LL UL Anti-HBs 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: Seroprotection rates and GMTs for Anti-Polio 1, Anti-Polio 2 and Anti-Polio 3 (ATP cohort for 10

11 persistence) 8 GMT Antibody Timing N n % LL UL value LL UL Anti-Polio 1 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti- Polio 2 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster Anti- Polio 3 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster GMT = geometric mean titer n/%= number/percentage of subjects with titer within the specified range Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-PRP antibodies (ATP cohort for persistence) 0.15 g/ml 1 g/ml GMC 95% CI Antibody Timing N n % LL UL n % LL UL value LL UL Anti-PRP 10PnEPI PIII(M3) Pre-booster PnEPI PIII(M3) Pre-booster Pn246 PIII(M5) Pre-booster Pn246 PIII(M5) Pre-booster n/%= number/percentage of subjects with concentration within the specified range Secondary Outcome Variables: Seropositivity rates and GMCs for ANTI-1, ANTI-4, ANTI-5, ANTI-6B, ANTI-7F, ANTI-9V, 11

12 ANTI-14, ANTI-18C, ANTI-19F and ANTI-23F antibodies (22F-inhibition ELISA), (ATP cohort for immunogenicity) 0.05 g/ml 0.20 g/ml GMC 95% CI Antibody Timing N n % LL UL n % LL UL value LL UL Anti-1 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-4 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-5 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-6B 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-7F 10PnEPI PIII(M3) Pre-booster Post-booster

13 7PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-9V 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-14 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-18C 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-19F 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5)

14 Pre-booster Post-booster Anti-23F 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster n/%= number/percentage of subjects with concentration within the specified range Post-booster = Post-booster vaccination blood sample - booster phase Secondary Outcome Variables: Seropositivity rates and GMCs for ANTI-6A and ANTI-19A antibodies (22F-inhibition ELISA), per schedule (ATP cohort for immunogenicity) 0.05 g/ml 0.20 g/ml GMC 95% CI Antibody Timing N n % LL UL n % LL UL val ue LL UL Anti-6A 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Anti-19A 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster n/%= number/percentage of subjects with concentration within the specified range 14

15 Post-booster = Post-booster vaccination blood sample - booster phase Secondary Outcome Variables: 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, per schedule (ATP cohort for immunogenicity) 8 GMT Antibody Timing N n % LL UL value LL UL Opsono-1 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-4 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-5 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-6B 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5)

16 Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-7F 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-9V 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-14 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-18C 10PnEPI PIII(M3) Pre-booster Post-booster PnEPI PIII(M3) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Pn246 PIII(M5) Pre-booster Post-booster Opsono-19F 10PnEPI PIII(M3)