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.: 107046 (10PN-PD-DIT-007 BST:001) Title: A phase IIIa single-blind, controlled multicentre study to assess the safety, reactogenicity and immunogenicity of GSK Biologicals 10-valent pneumococcal conjugate vaccine or Prevenar when given as a fourth dose between 12-18 months of age in children previously vaccinated in infancy in the primary study -PD-DIT-001 (105553) with either GSK Biologicals 10-valent pneumococcal conjugate vaccine or Prevenar. -PD-DiT: GlaxoSmithKline (GSK) Biologicals 10-valent pneumococcal conjugate vaccine () Prevenar: Wyeth s 7-valent pneumococcal conjugate vaccine () Rationale: The aim of this study was to assess the safety and immunogenicity of a booster dose of the -PD-DiT vaccine, co-administered with DTPa-HBV-IPV/Hib, at 12 to 18 months of age, in subjects primed in study 10PN-PD-DIT- 001 (105553). The persistence of antibodies prior to the booster vaccination was also evaluated. DTPa-HBV-IPV/Hib: GSK Biologicals combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated poliovirus and Haemophilus influenzae type b vaccine (Infanrix TM hexa). For results on the primary study, please refer to -PD-DIT-001 (105553) Phase: III Study Period: 25 September 2006 to 17 November 2007 (including the extended safety follow-up) Study Design: Multi-centre, partially-randomized*, single-blinded and controlled study with 3 parallel groups. * Subjects received the same lot of the vaccine as in the primary study 10PN-PD-DIT-001 (105553). Only subjects having received vaccine in the primary study were randomized with a 3:1 ratio to receive a booster dose of either the vaccine (one of the 3 different lots used in the primary vaccination study) or vaccine. Some of the subjects primed with were diverted to the 022 booster study to evaluate the co-administration with a combined measles mumps-rubella-varicella vaccine. Centres: Study conducted in 35 centres: 16 in Finland, 13 in France and 6 in Poland Indication: Booster vaccination against Streptococcus pneumoniae, diphtheria, tetanus, pertussis, Hib, hepatitis B and polio virus types 1 2 3 in children 12 to 18 months old. Treatment: The study groups were as follows: - Group: subjects primed with at least one dose of received a single dose of vaccine. Group: subjects primed with at least one dose of vaccine received a single dose of vaccine. Group: subjects primed with at least one dose of vaccine received a single dose of vaccine. Pneumococcal vaccines were co-administered with DTPa-HBV-IPV/Hib vaccine. All vaccines were injected intramuscularly into the thigh or deltoid region, -PD-DiT and in the right side and DTPa-HBV-IPV/Hib in the left side. Objectives: To demonstrate that a booster dose of -PD-DiT vaccine was non-inferior to vaccine, both coadministered with DTPa-HBV-IPV/Hib vaccine, in terms of post-immunization febrile reactions with rectal temperature > 39.0 C. 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 candidate vaccine group compared to the control group that would exceed a pre-defined limit of 10%, considered to be clinically acceptable. Primary Outcome/Efficacy Variable: Occurrence of fever with rectal temperature > 39.0 C within 4 days (Day 0-3) after the booster vaccination. Secondary Outcome/Efficacy Variable(s): Safety: Occurrence of solicited local symptoms (any and grade 3) within 4 days (Day 0-3) after the booster vaccination. Occurrence of solicited general symptoms (any and grade 3) within 4 days (Day 0-3) after the booster vaccination. Occurrence of unsolicited adverse events (AEs) within 31 days (Day 0-30) after the booster vaccination. Occurrence of serious adverse events (SAEs) throughout the active phase of the study, within 31 days after the booster vaccination (Day 0-30). Occurrence of serious adverse events during the extended 5-month safety follow-up *. * The SAEs analysis performed at the end of the safety follow-up included all SAEs from Day 0 until study conclusion. Immunogenicity: Prior to and one month after the booster vaccination with -PD-DiT conjugate vaccine or vaccine, co-
administered with DTPa-HBV-IPV/Hib vaccine: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.20 μg/ml. Antibody concentrations against 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 against protein D (anti-pd). 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. Prior to and one month after the administration of the booster dose of DTPa-HBV-IPV/Hib vaccine: Anti-diphtheria and anti-tetanus toxoids, anti-polyribosyl ribitol phosphate (anti-prp), anti-pertussis toxoid (anti-pt), anti-filamentous haemagglutinin (anti-fha) and anti-pertactin (anti-prn), anti-hepatitis B surface antigen (anti-hbs) antibody concentrations, and anti-polio type 1, 2 and 3 titres. Seropositivity status, defined as: - Anti-PT antibody concentrations 5 EL.U/mL. - Anti-FHA antibody concentrations 5 EL.U/mL. - Anti-PRN antibody concentrations 5 EL.U/mL. Seroprotection status, defined as: - Anti-diphtheria toxoid antibody concentrations 0.1 IU/mL. - Anti-tetanus toxoid 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 titres 8. - Anti-polio type 2 titres 8. - Anti-polio type 3 titres 8. Booster vaccine response to PT, FHA and PRN antigens one month after the booster vaccination; defined as appearance of antibodies in subjects who were seronegative prior to the booster vaccination or at least 2-fold increase of pre-booster vaccination antibody concentrations in subjects who were seropositive prior to the booster vaccination. Statistical Methods: Analyses were performed on the Primary total vaccinated cohort, on the Total vaccinated cohort, on the According-To- Protocol (ATP) cohort for persistence and on the ATP cohort for immunogenicity. - The Primary total vaccinated cohort included all vaccinated subjects from the primary study 10PN-PD-DIT-001 (105553), who were planned to be enrolled in the present booster vaccination study. - The Total vaccinated cohort included all vaccinated subjects. Thus, the Total vaccinated cohort for analysis of safety included all subjects with vaccine administration documented. - The ATP cohort for persistence included all subjects who had received the full 3-dose primary course in study 10PN-PD- DIT-001 (105553), who had received their study vaccine according to their planned assignment, for whom administration route of study vaccine was known, who had not received a vaccine not specified or forbidden in the protocol and 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) and with available immunogenicity data This included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after booster vaccination. Analysis of immunogenicity Descriptive assessments of pneumococcal antibody persistence were performed on the ATP cohort for persistence and descriptive analyses of booster response were performed on the ATP cohort for immunogenicity. Persistence: The tables were generated according to the primary phase treatment groups, for each pneumococcal serotype and for the following available blood sampling time points: post dose III blood sample (primary phase) and pre-booster vaccination blood sample (booster phase). Geometric mean antibody concentrations or geometric mean titres (GMCs or GMTs) with 95% confidence intervals (CIs) and seropositivity/seroprotection rates with exact 95% CIs were tabulated for each pneumococcal serotype and for Protein D. Antibody concentrations/titres below the cut-off of the assay were given an arbitrary value of half the cut-off for the purpose of GMC/GMT calculation. Booster response:
The tables were generated according to the booster phase treatment groups, for each pneumococcal serotype, for anti- PD, anti-diphtheria, anti-tetanus toxoids, anti-prp, anti-pt, anti-fha, anti-prn and anti-hbs and for the following blood sampling time points: post-dose 3 blood sample (primary phase), pre-booster vaccination blood sample (booster phase), post-booster vaccination blood sample (booster phase). GMCs or GMTs with 95% CIs and seropositivity/seroprotection rates with exact 95% CIs were tabulated. Analysis of safety Analysis of the SAEs between the end of the primary study up to booster dose was done on the Primary total vaccinated cohort. The other safety analyses were performed on the Total vaccinated cohort for the booster phase. Standardized asymptotic 95% CI for the difference between groups (- minus ), in terms of percentage of subjects with rectal temperature > 39.0 C, within 4 days (Day 0-3) after booster vaccination, was computed. The primary objective was reached if the upper limit of the 95% CI for the difference between groups (- minus ) was < 10%. The percentage of subjects with each individual solicited local and general symptom during the 4-day (Day 0-3) solicited follow-up period was tabulated with exact 95% CI. The same calculations were performed for symptoms rated as grade 3 and for general symptoms with causal relationship to vaccination. The proportion of subjects with at least one report of unsolicited AE classified by the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms and reported within 31 days (Day 0-30) after vaccination was tabulated. SAEs were also tabulated according to MedDRA preferred terms; 3 tables were generated: (1) one from priming up to booster dose, (2) one for SAEs occurring within 31 days after the booster dose and (3) one from the booster dose up to the end of the extended safety follow-up period, therefore also including the SAEs of the previous table.. Study Population: Approximately 1200 male or female subjects between and including, 12 and 18 months of age at the time of the booster vaccination, who participated in the primary vaccination study 10PN-PD-DIT-001 (105553) and received at least one dose of either pneumococcal conjugate vaccines (-PD-DIT or vaccine) were to be enrolled in this study. The other subjects who had participated in the study 105553 were invited to take part in a separate booster study 10PN-PD-DIT-022 BST:001. Subjects were free of obvious health problems as established by medical history and clinical examination before entering into the study. Subjects who were administered any additional pneumococcal or DTPa-combined vaccines since the end of the primary study 10PN-PD-DIT-001 (105553) were excluded. Written informed consent was obtained from the parent or guardian of the subject prior to the performance of any study-specific procedures. Active Phase Number of subjects - Group Group Group Planned, N 800 100 300 Randomised, N (Total Vaccinated Cohort) 737 92 283 Completed, n (%) 736 (99.9) 91 (98.9) 282 (99.6) Total Number Subjects Withdrawn, n (%) 1 (0.1) 1 (1.1) 1 (0.4) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not applicable Not applicable Not applicable Withdrawn for other reasons, n (%) 1 (0.1) 1 (1.1) 1 (0.4) Demographics - Group Group Group N (Total Vaccinated Cohort) 737 92 283 Females:Males 377:360 42:50 149:134 Mean Age, months (SD) 15.3 (2.08) 14.2 (2.26) 14.2 (2.23) White Caucasian/European heritage, n (%) 713 (96.7) 91 (98.9) 278 (98.2) Number of subjects - Group Group Group Subjects in Total Vaccinated Cohort (active phase), N) 737 92 283 Subjects in ESFU cohort, n (%) 726 91 282 Subjects not contacted for ESFU phase, n (%) 11 (1.5) 1 (1.1) 1 (0.4) Not contacted due to consent withdrawal, n (%) 0 (0.0) 0 (0.0) 0 (0.0) Not contacted due to lost to follow up, n (%) 11 (1.5) 1 (1.1) 1 (0.4) Extended Safety follow-up Demographics - Group Group Group N (ESFU cohort) 726 91 282 Females:Males 368:358 42:49 148:134 Mean Age, months (SD) 21.6 (2.22) 20.3 (2.38) 20.5 (2.42) White - Caucasian / European heritage, n (%) 702 (96.7) 90 (98.9) 277 (98.2) Primary Efficacy Results:
Difference between groups (- minus ) in percentage of subjects with rectal temperature > 39.0 C during the 4-day (Day 0-3) post-vaccination period (Total vaccinated cohort) Symptoms Type - Group Group Difference in percentage (- Group minus Group) N n % N n % % 95% CI LL UL Fever (rectal temperature) > 39.0 C 735 24 3.3 91 7 7.7-4.43-11.85-0.21* N = number of subjects with the documented dose n (%) = number (percentage) of subjects with rectal temperature > 39.0 C 95% CI = standardized asymptotic 95% confidence interval, LL = Lower Limit, UL = Upper Limit * The primary objective was reached as the upper limit of the 95% CI for the difference between groups (- minus ), in terms of percentage of subjects reporting fever with rectal temperature > 39.0 C after the booster vaccination, was below the pre-defined limit of 10%. 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) (ATP cohort for persistence) 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 - PIII(M3) 359 359 100 99.0 100 349 97.2 94.9 98.7 1.02 0.93 1.11 Pre-booster 344 306 89.0 85.2 92.1 125 36.3 31.2 41.7 0.14 0.13 0.16 PIII(M3) 226 16 7.1 4.1 11.2 8 3.5 1.5 6.9 0.03 0.03 0.03 Pre-booster 218 38 17.4 12.6 23.1 6 2.8 1.0 5.9 0.03 0.03 0.04 Anti-4 - PIII(M3) 361 359 99.4 98.0 99.9 352 97.5 95.3 98.9 1.48 1.36 1.63 Pre-booster 347 333 96.0 93.3 97.8 197 56.8 51.4 62.1 0.23 0.21 0.26 PIII(M3) 226 226 100 98.4 100 226 100 98.4 100 2.75 2.49 3.03 Pre-booster 212 209 98.6 95.9 99.7 153 72.2 65.6 78.1 0.33 0.29 0.37 Anti-5 - PIII(M3) 360 360 100 99.0 100 355 98.6 96.8 99.5 1.68 1.54 1.82 Pre-booster 349 340 97.4 95.2 98.8 232 66.5 61.3 71.4 0.27 0.24 0.30 PIII(M3) 227 40 17.6 12.9 23.2 8 3.5 1.5 6.8 0.03 0.03 0.04 Pre-booster 221 84 38.0 31.6 44.8 19 8.6 5.3 13.1 0.04 0.04 0.05 Anti-6B - PIII(M3) 357 319 89.4 85.7 92.4 243 68.1 63.0 72.9 0.34 0.30 0.39 Pre-booster 338 319 94.4 91.4 96.6 224 66.3 61.0 71.3 0.30 0.27 0.35 PIII(M3) 225 213 94.7 90.9 97.2 178 79.1 73.2 84.2 0.58 0.49 0.68 Pre-booster 209 186 89.0 83.9 92.9 92 44.0 37.2 51.0 0.20 0.17 0.24 Anti-7F - PIII(M3) 361 360 99.7 98.5 100 357 98.9 97.2 99.7 1.72 1.59 1.86 Pre-booster 345 343 99.4 97.9 99.9 311 90.1 86.5 93.1 0.56 0.52 0.62 PIII(M3) 228 61 26.8 21.1 33.0 14 6.1 3.4 10.1 0.04 0.03 0.04 Pre-booster 221 30 13.6 9.3 18.8 7 3.2 1.3 6.4 0.03 0.03 0.03 Anti-9V - PIII(M3) 359 359 100 99.0 100 352 98.1 96.0 99.2 1.29 1.19 1.40 Pre-booster 349 346 99.1 97.5 99.8 293 84.0 79.7 87.6 0.53 0.47 0.59 PIII(M3) 227 226 99.6 97.6 100 225 99.1 96.9 99.9 2.63 2.36 2.92 Pre-booster 210 209 99.5 97.4 100 195 92.9 88.5 95.9 0.71 0.63 0.79 Anti-14 - PIII(M3) 358 357 99.7 98.5 100 354 98.9 97.2 99.7 2.73 2.49 2.99 Pre-booster 341 330 96.8 94.3 98.4 271 79.5 74.8 83.6 0.65 0.56 0.76 PIII(M3) 227 227 100 98.4 100 225 99.1 96.9 99.9 4.30 3.77 4.91 Pre-booster 208 206 99.0 96.6 99.9 198 95.2 91.3 97.7 1.41 1.21 1.64 Anti-18C - PIII(M3) 358 356 99.4 98.0 99.9 337 94.1 91.2 96.3 1.58 1.41 1.77 Pre-booster 346 340 98.3 96.3 99.4 244 70.5 65.4 75.3 0.31 0.28 0.34 PIII(M3) 227 226 99.6 97.6 100 224 98.7 96.2 99.7 2.39 2.13 2.69 Pre-booster 217 214 98.6 96.0 99.7 169 77.9 71.8 83.2 0.35 0.31 0.39 Anti-19F - PIII(M3) 359 357 99.4 98.0 99.9 344 95.8 93.2 97.6 2.05 1.82 2.31 Pre-booster 352 343 97.4 95.2 98.8 274 77.8 73.1 82.1 0.52 0.45 0.61 PIII(M3) 228 228 100 98.4 100 227 99.6 97.6 100 3.29 2.98 3.63
Pre-booster 222 211 95.0 91.3 97.5 114 51.4 44.6 58.1 0.27 0.22 0.33 Anti-23F - PIII(M3) 359 342 95.3 92.5 97.2 298 83.0 78.7 86.7 0.54 0.48 0.61 Pre-booster 343 310 90.4 86.8 93.3 208 60.6 55.3 65.8 0.27 0.23 0.31 PIII(M3) 227 222 97.8 94.9 99.3 214 94.3 90.4 96.9 1.43 1.23 1.67 Pre-booster 210 201 95.7 92.0 98.0 142 67.6 60.8 73.9 0.33 0.28 0.39 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 (ATP cohort for persistence) Antibody Group Timing N 8 GMT n % 95% CI Value 95% CI LL UL LL UL Opsono-1 - PIII(M3) 166 106 63.9 56.0 71.2 23.8 18.7 30.2 Pre-booster 331 54 16.3 12.5 20.7 6.1 5.4 6.9 PIII(M3) 85 4 4.7 1.3 11.6 4.7 3.9 5.7 Pre-booster 212 12 5.7 3.0 9.7 4.9 4.4 5.5 Opsono-4 - PIII(M3) 165 164 99.4 96.7 100 734.4 627.8 859.3 Pre-booster 300 143 47.7 41.9 53.5 20.2 16.1 25.3 PIII(M3) 84 84 100 95.7 100 1043.6 872.0 1248.9 Pre-booster 194 110 56.7 49.4 63.8 31.3 23.0 42.7 Opsono-5 - PIII(M3) 161 146 90.7 85.1 94.7 59.1 48.3 72.3 Pre-booster 310 106 34.2 28.9 39.8 8.2 7.2 9.3 PIII(M3) 84 3 3.6 0.7 10.1 4.6 3.9 5.3 Pre-booster 206 5 2.4 0.8 5.6 4.2 4.0 4.5 Opsono-6B - PIII(M3) 160 151 94.4 89.6 97.4 489.4 385.9 620.7 Pre-booster 289 169 58.5 52.6 64.2 59.1 43.8 79.8 PIII(M3) 85 81 95.3 88.4 98.7 997.8 705.8 1410.4 Pre-booster 198 100 50.5 43.3 57.7 40.3 28.0 58.1 Opsono-7F - PIII(M3) 163 162 99.4 96.6 100 2291.3 1903.0 2758.9 Pre-booster 299 236 78.9 73.9 83.4 379.5 281.9 510.9 PIII(M3) 84 13 15.5 8.5 25.0 9.0 5.9 13.9 Pre-booster 196 68 34.7 28.1 41.8 29.4 19.7 43.9 Opsono-9V - PIII(M3) 166 166 100 97.8 100 1373.2 1161.6 1623.4 Pre-booster 314 305 97.1 94.6 98.7 295.2 258.2 337.4 PIII(M3) 85 85 100 95.8 100 1200.4 958.4 1503.5 Pre-booster 206 202 98.1 95.1 99.5 303.7 256.9 359.0 Opsono-14 - PIII(M3) 165 165 100 97.8 100 1040.6 870.5 1243.9 Pre-booster 304 253 83.2 78.5 87.2 189.8 151.8 237.2 PIII(M3) 85 84 98.8 93.6 100 1843.4 1392.8 2439.9 Pre-booster 200 179 89.5 84.4 93.4 286.2 225.0 364.1 Opsono-18C - PIII(M3) 164 153 93.3 88.3 96.6 138.3 111.8 171.2 Pre-booster 314 94 29.9 24.9 35.3 8.9 7.6 10.4 PIII(M3) 84 80 95.2 88.3 98.7 209.1 158.4 276.0 Pre-booster 206 63 30.6 24.4 37.4 9.1 7.5 11.1 Opsono-19F - PIII(M3) 166 149 89.8 84.1 93.9 168.6 125.5 226.5 Pre-booster 322 146 45.3 39.8 51.0 10.5 8.9 12.3 PIII(M3) 85 79 92.9 85.3 97.4 50.5 37.9 67.4 Pre-booster 207 34 16.4 11.7 22.2 6.6 5.5 8.1 Opsono-23F - PIII(M3) 162 153 94.4 89.7 97.4 972.3 751.3 1258.2 Pre-booster 310 218 70.3 64.9 75.4 167.5 123.6 227.0 PIII(M3) 83 82 98.8 93.5 100 4783.7 3758.9 6088.0
Pre-booster 200 159 79.5 73.2 84.9 343.3 238.0 495.3 n (%) = number (percentage) of subjects with antibody titre within the specified range Seropositivity rates and GMCs for anti-pd antibodies (ATP cohort for persistence) Group Timing N 100 EL.U/mL GMC (EL.U/mL) n % 95% CI Value 95% CI LL UL LL UL - PIII(M3) 357 355 99.4 98.0 99.9 1564.8 1430.2 1712.1 Pre-booster 343 325 94.8 91.8 96.9 553.0 492.4 621.0 PIII(M3) 222 42 18.9 14.0 24.7 67.3 61.3 73.9 Pre-booster 203 51 25.1 19.3 31.7 75.4 67.4 84.4 n (%) = number(percentage) of subjects with antibody concentration within the specified range 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) (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) 348 348 100 98.9 100 338 97.1 94.8 98.6 1.02 0.94 1.12 Pre-booster 338 302 89.3 85.6 92.4 123 36.4 31.3 41.8 0.14 0.13 0.16 Post-booster 342 342 100 98.9 100 340 99.4 97.9 99.9 1.53 1.40 1.68 PIII(M3) 90 9 10.0 4.7 18.1 4 4.4 1.2 11.0 0.03 0.03 0.03 Pre-booster 82 14 17.1 9.7 27.0 3 3.7 0.8 10.3 0.03 0.03 0.04 Post-booster 81 23 28.4 18.9 39.5 4 4.9 1.4 12.2 0.04 0.03 0.05 PIII(M3) 133 6 4.5 1.7 9.6 3 2.3 0.5 6.5 0.03 0.03 0.03 Pre-booster 133 23 17.3 11.3 24.8 3 2.3 0.5 6.5 0.03 0.03 0.04 Post-booster 133 131 98.5 94.7 99.8 113 85.0 77.7 90.6 0.67 0.56 0.80 PIII(M3) 350 348 99.4 98.0 99.9 341 97.4 95.2 98.8 1.48 1.35 1.63 Pre-booster 342 329 96.2 93.6 98.0 196 57.3 51.9 62.6 0.23 0.21 0.26 Post-booster 343 343 100 98.9 100 342 99.7 98.4 100 3.35 3.06 3.67 PIII(M3) 90 90 100 96.0 100 90 100 96.0 100 2.59 2.22 3.03 Pre-booster 78 78 100 95.4 100 53 67.9 56.4 78.1 0.30 0.25 0.37 Post-booster 88 88 100 95.9 100 88 100 95.9 100 4.40 3.75 5.15 PIII(M3) 132 132 100 97.2 100 132 100 97.2 100 2.92 2.58 3.31 Pre-booster 131 129 98.5 94.6 99.8 99 75.6 67.3 82.7 0.35 0.30 0.41 Post-booster 133 133 100 97.3 100 133 100 97.3 100 4.47 3.85 5.19 PIII(M3) 349 349 100 98.9 100 344 98.6 96.7 99.5 1.68 1.55 1.83 Pre-booster 344 335 97.4 95.1 98.8 231 67.2 61.9 72.1 0.27 0.25 0.30 Post-booster 342 342 100 98.9 100 340 99.4 97.9 99.9 2.20 2.00 2.42 PIII(M3) 90 19 21.1 13.2 31.0 4 4.4 1.2 11.0 0.03 0.03 0.04 Pre-booster 84 31 36.9 26.6 48.1 5 6.0 2.0 13.3 0.04 0.04 0.05 Post-booster 82 40 48.8 37.6 60.1 5 6.1 2.0 13.7 0.05 0.04 0.07 PIII(M3) 133 20 15.0 9.4 22.3 3 2.3 0.5 6.5 0.03 0.03 0.03 Pre-booster 134 53 39.6 31.2 48.4 14 10.4 5.8 16.9 0.05 0.04 0.05 Post-booster 133 131 98.5 94.7 99.8 114 85.7 78.6 91.2 0.74 0.60 0.90 PIII(M3) 347 310 89.3 85.6 92.4 235 67.7 62.5 72.6 0.34 0.30 0.39 Pre-booster 333 316 94.9 92.0 97.0 223 67.0 61.6 72.0 0.31 0.27 0.35
Anti-7F Anti-9V Anti-14 - - - Anti-18C - Anti-19F Anti-23F - - Post-booster 341 336 98.5 96.6 99.5 329 96.5 93.9 98.2 1.94 1.74 2.17 PIII(M3) 89 84 94.4 87.4 98.2 66 74.2 63.8 82.9 0.51 0.39 0.67 Pre-booster 75 64 85.3 75.3 92.4 23 30.7 20.5 42.4 0.14 0.11 0.19 Post-booster 87 86 98.9 93.8 100 85 97.7 91.9 99.7 3.53 2.83 4.41 PIII(M3) 133 126 94.7 89.5 97.9 111 83.5 76.0 89.3 0.64 0.51 0.79 Pre-booster 131 120 91.6 85.5 95.7 69 52.7 43.8 61.5 0.26 0.20 0.33 Post-booster 133 132 99.2 95.9 100 131 98.5 94.7 99.8 1.74 1.48 2.05 PIII(M3) 350 349 99.7 98.4 100 346 98.9 97.1 99.7 1.74 1.61 1.89 Pre-booster 340 338 99.4 97.9 99.9 308 90.6 87.0 93.5 0.57 0.52 0.62 Post-booster 342 342 100 98.9 100 342 100 98.9 100 3.50 3.25 3.76 PIII(M3) 90 24 26.7 17.9 37.0 2 2.2 0.3 7.8 0.04 0.03 0.04 Pre-booster 85 12 14.1 7.5 23.4 4 4.7 1.3 11.6 0.03 0.03 0.04 Post-booster 85 14 16.5 9.3 26.1 6 7.1 2.6 14.7 0.04 0.03 0.05 PIII(M3) 134 35 26.1 18.9 34.4 10 7.5 3.6 13.3 0.04 0.03 0.05 Pre-booster 133 18 13.5 8.2 20.5 3 2.3 0.5 6.5 0.03 0.03 0.03 Post-booster 133 130 97.7 93.5 99.5 127 95.5 90.4 98.3 1.83 1.49 2.24 PIII(M3) 349 349 100 98.9 100 342 98.0 95.9 99.2 1.29 1.19 1.40 Pre-booster 344 341 99.1 97.5 99.8 291 84.6 80.3 88.2 0.54 0.48 0.60 Post-booster 340 340 100 98.9 100 340 100 98.9 100 3.25 2.99 3.53 PIII(M3) 90 89 98.9 94.0 100 88 97.8 92.2 99.7 2.46 2.03 2.98 Pre-booster 77 76 98.7 93.0 100 70 90.9 82.2 96.3 0.62 0.51 0.76 Post-booster 89 89 100 95.9 100 89 100 95.9 100 6.09 5.19 7.15 PIII(M3) 133 133 100 97.3 100 133 100 97.3 100 2.78 2.44 3.16 Pre-booster 130 130 100 97.2 100 123 94.6 89.2 97.8 0.78 0.68 0.89 Post-booster 133 133 100 97.3 100 133 100 97.3 100 1.94 1.73 2.19 PIII(M3) 347 346 99.7 98.4 100 343 98.8 97.1 99.7 2.76 2.51 3.03 Pre-booster 336 325 96.7 94.2 98.4 268 79.8 75.1 83.9 0.66 0.56 0.76 Post-booster 339 339 100 98.9 100 336 99.1 97.4 99.8 5.56 5.01 6.18 PIII(M3) 90 90 100 96.0 100 88 97.8 92.2 99.7 3.81 3.03 4.81 Pre-booster 75 74 98.7 92.8 100 70 93.3 85.1 97.8 1.06 0.82 1.38 Post-booster 86 86 100 95.8 100 86 100 95.8 100 9.29 7.85 10.99 PIII(M3) 133 133 100 97.3 100 133 100 97.3 100 4.76 4.06 5.57 Pre-booster 130 129 99.2 95.8 100 125 96.2 91.3 98.7 1.69 1.40 2.03 Post-booster 133 133 100 97.3 100 133 100 97.3 100 4.76 4.12 5.49 PIII(M3) 348 346 99.4 97.9 99.9 328 94.3 91.3 96.5 1.59 1.42 1.79 Pre-booster 341 335 98.2 96.2 99.4 240 70.4 65.2 75.2 0.30 0.28 0.34 Post-booster 343 343 100 98.9 100 343 100 98.9 100 5.01 4.60 5.46 PIII(M3) 90 90 100 96.0 100 89 98.9 94.0 100 2.42 2.03 2.89 Pre-booster 83 81 97.6 91.6 99.7 60 72.3 61.4 81.6 0.32 0.26 0.39 Post-booster 87 87 100 95.8 100 87 100 95.8 100 5.21 4.44 6.11 PIII(M3) 134 133 99.3 95.9 100 132 98.5 94.7 99.8 2.42 2.07 2.82 Pre-booster 131 130 99.2 95.8 100 107 81.7 74.0 87.9 0.37 0.32 0.43 Post-booster 134 133 99.3 95.9 100 133 99.3 95.9 100 4.98 4.17 5.93 PIII(M3) 349 347 99.4 97.9 99.9 335 96.0 93.4 97.8 2.07 1.83 2.33 Pre-booster 347 338 97.4 95.1 98.8 272 78.4 73.7 82.6 0.53 0.46 0.61 Post-booster 343 343 100 98.9 100 341 99.4 97.9 99.9 6.05 5.46 6.71 PIII(M3) 90 90 100 96.0 100 90 100 96.0 100 3.13 2.66 3.67 Pre-booster 85 82 96.5 90.0 99.3 38 44.7 33.9 55.9 0.23 0.17 0.31 Post-booster 87 87 100 95.8 100 87 100 95.8 100 3.35 2.83 3.97 PIII(M3) 134 134 100 97.3 100 133 99.3 95.9 100 3.46 3.04 3.95 Pre-booster 134 127 94.8 89.5 97.9 76 56.7 47.9 65.2 0.31 0.24 0.41 Post-booster 134 134 100 97.3 100 131 97.8 93.6 99.5 5.06 4.24 6.04 PIII(M3) 349 332 95.1 92.3 97.1 288 82.5 78.1 86.4 0.54 0.47 0.61 Pre-booster 338 305 90.2 86.6 93.2 206 60.9 55.5 66.2 0.27 0.23 0.31 Post-booster 341 338 99.1 97.5 99.8 332 97.4 95.0 98.8 2.38 2.13 2.66
PIII(M3) 90 88 97.8 92.2 99.7 83 92.2 84.6 96.8 1.25 0.96 1.62 Pre-booster 77 75 97.4 90.9 99.7 43 55.8 44.1 67.2 0.24 0.19 0.31 Post-booster 88 87 98.9 93.8 100 87 98.9 93.8 100 6.67 5.38 8.26 PIII(M3) 133 130 97.7 93.5 99.5 127 95.5 90.4 98.3 1.61 1.32 1.95 Pre-booster 130 125 96.2 91.3 98.7 98 75.4 67.1 82.5 0.40 0.32 0.50 Post-booster 132 130 98.5 94.6 99.8 128 97.0 92.4 99.2 2.42 1.99 2.95 Post-booster = post-booster vaccination blood sample (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 (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT n % 95% CI Value 95% CI LL UL LL UL Opsono-1 - PIII(M3) 164 105 64.0 56.2 71.4 23.8 18.7 30.3 Pre-booster 326 53 16.3 12.4 20.7 6.1 5.4 6.9 Post-booster 301 274 91.0 87.2 94.0 192.2 157.5 234.6 PIII(M3) 16 1 6.3 0.2 30.2 5.0 3.1 8.1 Pre-booster 83 5 6.0 2.0 13.5 5.0 4.1 6.0 Post-booster 83 3 3.6 0.8 10.2 4.3 3.9 4.7 PIII(M3) 68 2 2.9 0.4 10.2 4.5 3.7 5.5 Pre-booster 126 7 5.6 2.3 11.1 4.9 4.2 5.8 Post-booster 121 38 31.4 23.3 40.5 8.3 6.7 10.4 Opsono-4 - PIII(M3) 163 162 99.4 96.6 100 735.2 627.2 861.8 Pre-booster 295 141 47.8 42.0 53.7 20.3 16.2 25.5 Post-booster 297 297 100 98.8 100 1856.3 1666.1 2068.0 PIII(M3) 16 16 100 79.4 100 1042.1 658.8 1648.3 Pre-booster 79 41 51.9 40.4 63.3 24.5 15.4 38.8 Post-booster 81 81 100 95.5 100 2812.6 2282.5 3465.9 PIII(M3) 67 67 100 94.6 100 1034.4 844.9 1266.3 Pre-booster 112 68 60.7 51.0 69.8 37.8 24.8 57.7 Post-booster 123 123 100 97.0 100 1528.9 1286.5 1817.0 Opsono-5 - PIII(M3) 159 145 91.2 85.7 95.1 59.6 48.8 72.9 Pre-booster 305 105 34.4 29.1 40.1 8.2 7.2 9.4 Post-booster 299 288 96.3 93.5 98.1 144.1 122.1 170.0 PIII(M3) 16 1 6.3 0.2 30.2 4.9 3.2 7.6 Pre-booster 79 3 3.8 0.8 10.7 4.4 3.9 4.9 Post-booster 83 1 1.2 0.0 6.5 4.1 3.9 4.4 PIII(M3) 67 1 1.5 0.0 8.0 4.3 3.7 5.0 Pre-booster 124 2 1.6 0.2 5.7 4.1 3.9 4.3 Post-booster 122 45 36.9 28.3 46.1 9.5 7.5 11.9 Opsono-6B - PIII(M3) 158 149 94.3 89.5 97.4 493.8 388.4 627.9 Pre-booster 284 167 58.8 52.8 64.6 60.3 44.6 81.7 Post-booster 295 285 96.6 93.9 98.4 981.2 830.7 1159.1 PIII(M3) 16 16 100 79.4 100 1703.3 1091.7 2657.7 Pre-booster 75 40 53.3 41.4 64.9 51.4 27.1 97.5 Post-booster 79 78 98.7 93.1 100 3459.6 2535.7 4720.3 PIII(M3) 68 64 94.1 85.6 98.4 872.7 574.6 1325.5 Pre-booster 120 60 50.0 40.7 59.3 36.7 23.3 57.7 Post-booster 118 112 94.9 89.3 98.1 640.2 480.7 852.7 Opsono-7F - PIII(M3) 161 160 99.4 96.6 100 2282.6 1891.5 2754.5
Pre-booster 294 232 78.9 73.8 83.4 377.7 279.8 509.9 Post-booster 296 295 99.7 98.1 100 4330.3 3836.0 4888.3 PIII(M3) 16 3 18.8 4.0 45.6 10.0 3.3 30.7 Pre-booster 76 28 36.8 26.1 48.7 34.8 17.5 69.3 Post-booster 74 23 31.1 20.8 42.9 25.2 13.1 48.7 PIII(M3) 67 9 13.4 6.3 24.0 7.9 5.2 12.2 Pre-booster 117 38 32.5 24.1 41.8 25.3 15.4 41.6 Post-booster 118 116 98.3 94.0 99.8 2397.2 1929.2 2978.7 Opsono-9V - PIII(M3) 164 164 100 97.8 100 1390.2 1175.7 1643.9 Pre-booster 309 300 97.1 94.5 98.7 296.9 259.3 339.9 Post-booster 297 297 100 98.8 100 2343.5 2097.1 2618.7 PIII(M3) 16 16 100 79.4 100 1624.0 1030.4 2559.5 Pre-booster 81 78 96.3 89.6 99.2 305.5 227.1 411.0 Post-booster 79 79 100 95.4 100 5357.4 4212.5 6813.6 PIII(M3) 68 68 100 94.7 100 1112.8 856.1 1446.5 Pre-booster 122 121 99.2 95.5 100 305.1 248.7 374.4 Post-booster 120 120 100 97.0 100 886.8 747.7 1051.8 Opsono-14 - PIII(M3) 163 163 100 97.8 100 1046.6 873.8 1253.7 Pre-booster 299 248 82.9 78.2 87.0 188.1 149.9 235.9 Post-booster 304 304 100 98.8 100 2085.9 1868.0 2329.1 PIII(M3) 16 15 93.8 69.8 99.8 1873.4 699.2 5019.6 Pre-booster 79 66 83.5 73.5 90.9 201.6 129.4 314.2 Post-booster 82 82 100 95.6 100 2134.2 1689.1 2696.6 PIII(M3) 68 68 100 94.7 100 1836.2 1385.8 2433.0 Pre-booster 118 112 94.9 89.3 98.1 391.1 303.1 504.6 Post-booster 123 123 100 97.0 100 977.8 828.9 1153.5 Opsono-18C - PIII(M3) 162 151 93.2 88.2 96.6 139.4 112.4 172.9 Pre-booster 309 91 29.4 24.4 34.9 8.7 7.4 10.3 Post-booster 299 298 99.7 98.2 100 810.3 712.4 921.7 PIII(M3) 16 16 100 79.4 100 299.3 176.2 508.6 Pre-booster 82 28 34.1 24.0 45.4 10.4 7.4 14.7 Post-booster 76 76 100 95.3 100 968.7 724.1 1295.8 PIII(M3) 67 63 94.0 85.4 98.3 191.4 138.1 265.4 Pre-booster 121 35 28.9 21.0 37.9 8.5 6.6 10.9 Post-booster 121 119 98.3 94.2 99.8 610.7 480.3 776.4 Opsono-19F - PIII(M3) 164 147 89.6 83.9 93.8 170.2 126.3 229.3 Pre-booster 317 145 45.7 40.2 51.4 10.5 8.9 12.3 Post-booster 293 278 94.9 91.7 97.1 624.3 509.7 764.7 PIII(M3) 16 15 93.8 69.8 99.8 50.6 26.4 96.9 Pre-booster 81 12 14.8 7.9 24.4 5.9 4.5 7.8 Post-booster 80 74 92.5 84.4 97.2 287.8 190.8 434.3 PIII(M3) 68 63 92.6 83.7 97.6 48.3 35.0 66.6 Pre-booster 123 22 17.9 11.6 25.8 7.3 5.5 9.6 Post-booster 120 118 98.3 94.1 99.8 530.1 393.0 715.2 Opsono-23F - PIII(M3) 160 151 94.4 89.6 97.4 974.1 750.8 1263.8 Pre-booster 305 216 70.8 65.4 75.9 171.5 126.3 232.8 Post-booster 301 300 99.7 98.2 100 2830.1 2487.2 3220.3 PIII(M3) 16 16 100 79.4 100 6410.0 4518.4 9093.5 Pre-booster 77 57 74.0 62.8 83.4 205.8 110.1 384.6 Post-booster 80 79 98.8 93.2 100 13900.7 10177.4 18986.1 PIII(M3) 66 65 98.5 91.8 100 4452.7 3324.6 5963.5 Pre-booster 120 102 85.0 77.3 90.9 532.9 344.4 824.7 Post-booster 122 120 98.4 94.2 99.8 2828.8 2234.3 3581.6
Post-booster = post-booster vaccination blood sample (booster phase) Seropositivity rates and GMCs for anti-pd antibodies (ATP cohort for immunogenicity) Group Timing N 100 EL.U/mL GMC (EL.U/mL) n % 95% CI Value 95% CI LL UL LL UL - PIII(M3) 347 345 99.4 97.9 99.9 1572.4 1436.4 1721.3 Pre-booster 338 320 94.7 91.7 96.8 556.4 494.7 625.7 Post-booster 340 338 99.4 97.9 99.9 2887.6 2573.7 3239.8 PIII(M3) 89 18 20.2 12.4 30.1 67.4 58.9 77.2 Pre-booster 73 15 20.5 12.0 31.6 72.3 59.3 88.0 Post-booster 86 16 18.6 11.0 28.4 75.3 60.0 94.4 PIII(M3) 130 22 16.9 10.9 24.5 65.5 57.7 74.2 Pre-booster 127 36 28.3 20.7 37.0 78.1 67.8 89.9 Post-booster 134 67 50.0 41.2 58.8 125.5 103.4 152.4 Post-booster = post-booster vaccination blood sample (booster phase) Seroprotection rates and GMCs for anti-diphtheria and anti-tetanus antibodies (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 Antidiphtheria Antitetanus - PIII(M3) 339 338 99.7 98.4 100 1.176 1.064 1.300 Pre-booster 344 254 73.8 68.9 78.4 0.179 0.161 0.199 Post-booster 343 343 100 98.9 100 5.809 5.352 6.305 PIII(M3) 49 49 100 92.7 100 1.294 1.041 1.609 Pre-booster 34 30 88.2 72.5 96.7 0.291 0.200 0.424 Post-booster 45 45 100 92.1 100 6.272 4.883 8.055 PIII(M3) 124 124 100 97.1 100 1.412 1.236 1.613 Pre-booster 136 125 91.9 86.0 95.9 0.290 0.250 0.336 Post-booster 136 136 100 97.3 100 9.337 8.419 10.356 - PIII(M3) 339 339 100 98.9 100 2.192 2.041 2.354 Pre-booster 344 330 95.9 93.3 97.8 0.417 0.382 0.456 Post-booster 343 343 100 98.9 100 9.983 9.293 10.724 PIII(M3) 49 49 100 92.7 100 1.569 1.276 1.928 Pre-booster 35 29 82.9 66.4 93.4 0.261 0.187 0.364 Post-booster 46 46 100 92.3 100 4.280 3.294 5.562 PIII(M3) 124 123 99.2 95.6 100 1.494 1.314 1.698 Pre-booster 136 114 83.8 76.5 89.6 0.265 0.225 0.313 Post-booster 136 136 100 97.3 100 5.677 5.038 6.397 Post-booster = post-booster vaccination blood sample (booster phase) Seropositivity rates and GMCs for anti-pt, anti-fha and anti-prn antibodies (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 - PIII(M3) 338 338 100 98.9 100 46.1 43.2 49.2 Pre-booster 332 180 54.2 48.7 59.7 5.5 5.1 6.1 Post-booster 338 338 100 98.9 100 79.6 73.8 85.9 PIII(M3) 49 49 100 92.7 100 48.3 40.0 58.3 Pre-booster 34 22 64.7 46.5 80.3 7.3 5.2 10.3 Post-booster 46 46 100 92.3 100 76.0 60.4 95.7 PIII(M3) 122 122 100 97.0 100 47.2 42.5 52.5 Pre-booster 133 91 68.4 59.8 76.2 7.0 6.1 8.1 Post-booster 135 135 100 97.3 100 85.8 76.9 95.7 Anti-FHA - PIII(M3) 338 338 100 98.9 100 133.9 124.6 143.9 Pre-booster 343 333 97.1 94.7 98.6 27.1 24.4 30.1 Post-booster 343 343 100 98.9 100 357.7 332.6 384.7 PIII(M3) 49 49 100 92.7 100 142.7 114.8 177.3 Pre-booster 36 34 94.4 81.3 99.3 29.0 20.5 40.8 Post-booster 46 46 100 92.3 100 334.5 278.1 402.2 PIII(M3) 123 123 100 97.0 100 143.5 127.0 162.1 Pre-booster 135 132 97.8 93.6 99.5 35.5 29.7 42.3 Post-booster 136 136 100 97.3 100 400.2 356.4 449.5 Anti-PRN - PIII(M3) 337 336 99.7 98.4 100 67.1 60.7 74.1 Pre-booster 344 251 73.0 67.9 77.6 9.1 8.2 10.1 Post-booster 342 342 100 98.9 100 248.9 226.5 273.4 PIII(M3) 49 49 100 92.7 100 78.1 63.9 95.4 Pre-booster 34 26 76.5 58.8 89.3 11.1 7.6 16.2 Post-booster 45 45 100 92.1 100 204.6 155.8 268.7 PIII(M3) 122 121 99.2 95.5 100 75.7 65.3 87.8 Pre-booster 136 111 81.6 74.1 87.7 12.1 10.1 14.6 Post-booster 135 135 100 97.3 100 276.5 239.1 319.7 Post-booster = post-booster vaccination blood sample (booster phase) Seroprotection rates and GMCs for anti-hbs antibodies (ATP cohort for immunogenicity) Group Timing N 10 miu/ml GMC (miu/ml) n % 95% CI Value 95% CI LL UL LL UL - PIII(M3) 331 325 98.2 96.1 99.3 478.5 414.4 552.5 Pre-booster 329 309 93.9 90.8 96.2 147.2 124.7 173.7 Post-booster 325 319 98.2 96.0 99.3 3869.1 3218.1 4651.8 PIII(M3) 47 46 97.9 88.7 99.9 405.4 260.4 630.9 Pre-booster 48 47 97.9 88.9 99.9 148.9 100.4 220.8 Post-booster 47 46 97.9 88.7 99.9 3132.2 1906.3 5146.5 PIII(M3) 120 119 99.2 95.4 100 455.6 360.5 575.7 Pre-booster 134 131 97.8 93.6 99.5 156.6 125.5 195.5 Post-booster 132 132 100 97.2 100 4358.6 3495.5 5434.8 Post-booster = post-booster vaccination blood sample (booster phase)
Seroprotection rates and GMTs for anti-polio 1, anti-polio 2 and anti-polio 3 (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT n % 95% CI Value 95% CI LL UL LL UL Anti-polio 1 - PIII(M3) 204 200 98.0 95.1 99.5 118.4 97.5 143.8 Pre-booster 318 252 79.2 74.4 83.6 25.3 21.9 29.3 Post-booster 279 278 99.6 98.0 100 904.4 779.7 1049.1 PIII(M3) 33 33 100 89.4 100 110.5 65.0 187.8 Pre-booster 48 38 79.2 65.0 89.5 21.2 15.0 30.0 Post-booster 42 42 100 91.6 100 819.3 552.9 1214.2 PIII(M3) 75 75 100 95.2 100 113.9 80.4 161.4 Pre-booster 131 104 79.4 71.4 86.0 27.1 20.7 35.4 Post-booster 121 121 100 97.0 100 1003.7 817.5 1232.3 Anti-polio 2 - PIII(M3) 201 190 94.5 90.4 97.2 69.1 56.7 84.3 Pre-booster 317 237 74.8 69.6 79.5 20.8 18.1 24.0 Post-booster 280 280 100 98.7 100 793.5 679.7 926.3 PIII(M3) 31 26 83.9 66.3 94.5 41.8 22.6 77.3 Pre-booster 46 25 54.3 39.0 69.1 12.9 8.8 18.9 Post-booster 43 43 100 91.8 100 495.7 300.2 818.5 PIII(M3) 71 66 93.0 84.3 97.7 64.5 42.9 97.1 Pre-booster 130 87 66.9 58.1 74.9 17.9 14.1 22.8 Post-booster 122 122 100 97.0 100 661.2 496.7 880.3 Anti-polio 3 - PIII(M3) 196 196 100 98.1 100 296.0 236.9 369.9 Pre-booster 262 216 82.4 77.3 86.8 33.7 28.5 39.8 Post-booster 270 269 99.6 98.0 100 1465.0 1257.1 1707.3 PIII(M3) 31 29 93.5 78.6 99.2 143.3 74.5 275.5 Pre-booster 39 30 76.9 60.7 88.9 25.8 16.7 39.8 Post-booster 41 41 100 91.4 100 1191.7 743.1 1911.3 PIII(M3) 72 72 100 95.0 100 211.3 150.4 297.0 Pre-booster 113 87 77.0 68.1 84.4 28.2 21.6 36.8 Post-booster 116 116 100 96.9 100 1646.5 1294.4 2094.5 Post-booster = post-booster vaccination blood sample (booster phase) Seroprotection rates and GMCs for anti-prp antibodies (ATP cohort for immunogenicity) 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 - PIII(M3) 335 323 96.4 93.8 98.1 242 72.2 67.1 77.0 2.061 1.803 2.357 Pre-booster 344 244 70.9 65.8 75.7 61 17.7 13.8 22.2 0.308 0.272 0.348 Post-booster 343 343 100 98.9 100 343 100 98.9 100 36.634 31.897 42.074 PIII(M3) 48 48 100 92.6 100 23 47.9 33.3 62.8 1.264 0.865 1.846 Pre-booster 39 22 56.4 39.6 72.2 4 10.3 2.9 24.2 0.231 0.151 0.353 Post-booster 46 45 97.8 88.5 99.9 45 97.8 88.5 99.9 25.731 15.870 41.719 PIII(M3) 121 116 95.9 90.6 98.6 58 47.9 38.8 57.2 1.090 0.865 1.375 Pre-booster 136 82 60.3 51.6 68.6 14 10.3 5.7 16.7 0.246 0.200 0.304 Post-booster 136 136 100 97.3 100 134 98.5 94.8 99.8 29.851 23.563 37.816
Post-booster = post-booster vaccination blood sample (booster phase) Booster vaccine response for anti-pt, anti-fha and anti-prn antibody concentrations, one month after booster dose (ATP cohort for immunogenicity) Antibody Group Pre-vaccination status Number of Responders subjects* n % 95% CI LL UL Anti-PT - S- 150 150 100 97.6 100 S+ 174 173 99.4 96.8 100 Total 324 323 99.7 98.3 100 S- 11 11 100 71.5 100 S+ 20 20 100 83.2 100 Total 31 31 100 88.8 100 S- 42 42 100 91.6 100 S+ 90 90 100 96.0 100 Total 132 132 100 97.2 100 Anti-FHA - S- 10 10 100 69.2 100 S+ 330 322 97.6 95.3 98.9 Total 340 332 97.6 95.4 99.0 S- 2 2 100 15.8 100 S+ 31 29 93.5 78.6 99.2 Total 33 31 93.9 79.8 99.3 S- 3 3 100 29.2 100 S+ 132 126 95.5 90.4 98.3 Total 135 129 95.6 90.6 98.4 Anti-PRN - S- 92 92 100 96.1 100 S+ 248 247 99.6 97.8 100 Total 340 339 99.7 98.4 100 S- 8 8 100 63.1 100 S+ 23 22 95.7 78.1 99.9 Total 31 30 96.8 83.3 99.9 S- 25 25 100 86.3 100 S+ 110 106 96.4 91.0 99.0 Total 135 131 97.0 92.6 99.2 * number of subjects with both pre and post vaccination results available n (%) = number (percentage) of responders S-/S+ = seronegative/seropositive subjects at pre-booster vaccination Total = subjects either seropositive or seronegative at pre-booster vaccination Booster vaccine response defined as : For initially seronegative subjects, antibody concentration at Post-booster 5 EL.U/mL For initially seropositive subjects, antibody concentration at Post-booster 2 fold the pre-booster vaccination antibody concentration 95% CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Incidence of solicited local symptoms reported during the 4-day (Day 0-3) post-vaccination period (Total vaccinated cohort) Symptom Intensity - Group Group Group N n % 95% CI N n % 95% CI N n % 95% CI LL UL LL UL LL UL Pain Any 735 452 61.5 57.9 65.0 91 48 52.7 42.0 63.3 282 150 53.2 47.2 59.1 Grade 3 735 47 6.4 4.7 8.4 91 3 3.3 0.7 9.3 282 18 6.4 3.8 9.9 Redness Any 735 451 61.4 57.7 64.9 91 59 64.8 54.1 74.6 282 153 54.3 48.2 60.2 > 30 mm 735 96 13.1 10.7 15.7 91 7 7.7 3.1 15.2 282 19 6.7 4.1 10.3 Swelling Any 735 338 46.0 42.3 49.7 91 42 46.2 35.6 56.9 282 112 39.7 34.0 45.7
> 30 mm 735 67 9.1 7.1 11.4 91 7 7.7 3.1 15.2 282 20 7.1 4.4 10.7 N = number of subjects with the documented dose n (%) = number (percentage) of subjects for whom the symptom was reported at least once 95%CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any solicited general symptom regardless of their intensity grade. Grade 3 pain = cried when limb was moved/ was spontaneously painful. Incidence of solicited general symptoms reported during the 4-day (Day 0-3) post-vaccination period (Total vaccinated cohort) Symptom Intensity/ relationship - Group Group Group N n % 95% CI N n % 95% CI N n % 95% CI LL UL LL UL LL UL Drowsiness Any 735 303 41.2 37.6 44.9 91 48 52.7 42.0 63.3 282 130 46.1 40.2 52.1 Grade 3 735 5 0.7 0.2 1.6 91 0 0.0 0.0 4.0 282 5 1.8 0.6 4.1 Related 735 302 41.1 37.5 44.7 91 48 52.7 42.0 63.3 282 126 44.7 38.8 50.7 Fever 38.0 C 735 245 33.3 29.9 36.9 91 33 36.3 26.4 47.0 282 112 39.7 34.0 45.7 (rectal > 39.0 C 735 24 3.3 2.1 4.8 91 7 7.7 3.1 15.2 282 10 3.5 1.7 6.4 temperature) > 40.0 C 735 1 0.1 0.0 0.8 91 2 2.2 0.3 7.7 282 3 1.1 0.2 3.1 Related 735 236 32.1 28.7 35.6 91 32 35.2 25.4 45.9 282 110 39.0 33.3 45.0 Irritability Any 735 438 59.6 55.9 63.2 91 55 60.4 49.6 70.5 282 176 62.4 56.5 68.1 Grade 3 735 15 2.0 1.1 3.3 91 2 2.2 0.3 7.7 282 12 4.3 2.2 7.3 Loss of appetite Related 735 427 58.1 54.4 61.7 91 55 60.4 49.6 70.5 282 172 61.0 55.0 66.7 Any 735 230 31.3 28.0 34.8 91 31 34.1 24.5 44.7 282 92 32.6 27.2 38.4 Grade 3 735 4 0.5 0.1 1.4 91 0 0.0 0.0 4.0 282 3 1.1 0.2 3.1 Related 735 222 30.2 26.9 33.7 91 30 33.0 23.5 43.6 282 91 32.3 26.8 38.1 N = number of subjects with the documented dose n (%) = number (percentage) of subjects for whom the symptom was reported at least once 95%CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any solicited general symptom regardless of their intensity grade or relationship to study 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 = general symptom considered by the investigator to be causally related to the study vaccination. Safety Results: Number (%) of subjects with unsolicited adverse events (Total vaccinated cohort) Most frequent* adverse events - On-Therapy (occurring within Day 0-30 following vaccination) - Group N = 737 Group N = 92 Group N = 283 Subjects with any AE(s), n (%) 188 (25.5) 32 (34.8) 99 (35.0) Rhinitis 28 (3.8) 4 (4.3) 19 (6.7) Upper respiratory tract infection 25 (3.4) 5 (5.4) 13 (4.6) Otitis media 16 (2.2) 4 (4.3) 11 (3.9) Pyrexia 14 (1.9) 3 (3.3) 12 (4.2) Diarrhoea 15 (2.0) 1 (1.1) 10 (3.5) Cough 7 (0.9) 3 (3.3) 14 (4.9) Bronchitis 11 (1.5) 4 (4.3) 7 (2.5) Injection site induration 1 (0.1) 7 (7.6) 7 (2.5) Nasopharyngitis 8 (1.1) 2 (2.2) 4 (1.4) Conjunctivitis 8 (1.1) 1 (1.1) 4 (1.4) Ear infection 6 (0.8) 2 (2.2) 5 (1.8) Gastroenteritis 9 (1.2) 2 (2.2) 2 (0.7) Pharyngitis 10 (1.4) 2 (2.2) 1 (0.4) Exanthema subitum 5 (0.7) 2 (2.2) 2 (0.7) Rash 5 (0.7) 2 (2.2) 0 (0.0) Teething 2 (0.3) 0 (0.0) 5 (1.8) * Detail of unsolicited AEs counting rule: > 30 subjects/treatment group and > = 3 groups, display the most frequent 10 primary preferred terms in each group. Safety Results: Number (%) of subjects with Serious Adverse Events (SAEs) between the end of the primary vaccination
study and the booster vaccination (Primary Total vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs (between the end of the - Group primary vaccination study and the N = 827 booster vaccination) Group & Group pooled N = 415 Subjects with any SAE(s), n (%) [n related] 59 (7.1) [0] 23 (5.5) [0] Pharyngitis 8 (1.0) [0] 5 (1.2) [0] Gastroenteritis 10 (1.2) [0] 2 (0.5) [0] Bronchitis chronic 5 (0.6) [0] 6 (1.4) [0] Diarrhoea 6 (0.7) [0] 2 (0.5) [0] Gastroenteritis rotavirus 4 (0.5) [0] 2 (0.5) [0] Bronchopneumonia 5 (0.6) [0] 0 (0.0) [0] Ear infection 5 (0.6) [0] 0 (0.0) [0] Pneumonia 3 (0.4) [0] 2 (0.5) [0] Urinary tract infection 4 (0.5) [0] 1 (0.2) [0] Bronchitis 3 (0.4) [0] 1 (0.2) [0] Febrile convulsion 2 (0.2) [0] 2 (0.5) [0] Nasopharyngitis 3 (0.4) [0] 1 (0.2) [0] Respiratory tract infection 2 (0.2) [0] 2 (0.5) [0] Head injury 3 (0.4) [0] 0 (0.0) [0] Laryngitis 2 (0.2) [0] 1 (0.2) [0] Otitis media acute 2 (0.2) [0] 1 (0.2) [0] Pyelonephritis 3 (0.4) [0] 0 (0.0) [0] Thermal burn 3 (0.4) [0] 0 (0.0) [0] Upper respiratory tract infection 1 (0.1) [0] 2 (0.5) [0] Dyspepsia 2 (0.2) [0] 0 (0.0) [0] Enteritis 2 (0.2) [0] 0 (0.0) [0] Oral herpes 1 (0.1) [0] 1 (0.2) [0] Otitis media 1 (0.1) [0] 1 (0.2) [0] Rash 2 (0.2) [0] 0 (0.0) [0] Skull fracture 2 (0.2) [0] 0 (0.0) [0] Anaemia 1 (0.1) [0] 0 (0.0) [0] Brain neoplasm 1 (0.1) [0] 0 (0.0) [0] Bronchiolitis 0 (0.0) [0] 1 (0.2) [0] Concussion 1 (0.1) [0] 0 (0.0) [0] Conjunctivitis 1 (0.1) [0] 0 (0.0) [0] Contusion 0 (0.0) [0] 1 (0.2) [0] Dehydration 1 (0.1) [0] 0 (0.0) [0] Dermatitis allergic 1 (0.1) [0] 0 (0.0) [0] Eczema infantile 0 (0.0) [0] 1 (0.2) [0] Enterocolitis haemorrhagic 1 (0.1) [0] 0 (0.0) [0] Foreign body aspiration 1 (0.1) [0] 0 (0.0) [0] Gastro oesophageal reflux disease 0 (0.0) [0] 1 (0.2) [0] Infantile spasms 1 (0.1) [0] 0 (0.0) [0] Intertrigo 1 (0.1) [0] 0 (0.0) [0] Intussusception 1 (0.1) [0] 0 (0.0) [0] Psychomotor retardation 1 (0.1) [0] 0 (0.0) [0] Pyrexia 1 (0.1) [0] 0 (0.0) [0] Skin exfoliation 1 (0.1) [0] 0 (0.0) [0] Subcutaneous haematoma 1 (0.1) [0] 0 (0.0) [0] Talipes 1 (0.1) [0] 0 (0.0) [0] Tongue neoplasm 1 (0.1) [0] 0 (0.0) [0] Tonic convulsion 1 (0.1) [0] 0 (0.0) [0] Tonsillitis 1 (0.1) [0] 0 (0.0) [0] Urticaria 1 (0.1) [0] 0 (0.0) [0]
Vomiting 1 (0.1) [0] 0 (0.0) [0] Wound 1 (0.1) [0] 0 (0.0) [0] Wound complication 1 (0.1) [0] 0 (0.0) [0] Fatal SAEs - Group N = 1214 Subjects with fatal SAEs, n (%) [related] 0 (0.0) [0] 0 (0.0) [0] Safety Results: Number (%) of subjects with SAEs within 31 days after booster dose (Total vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] Group & Group pooled N = 409 All SAEs (occurring within Day 0-30 following vaccination) - Group N = 737 Group N = 92 Group N = 283 Subjects with any SAE(s), n (%) [n related] 12(1.6) [0] 1 (1.1) [0] 4 (1.4) [1] Asthma 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Gastroenteritis 3 (0.4) [0] 0 (0.0) [0] 1 (0.4) [0] Bronchitis 1 (0.1) [0] 1 (1.1) [0] 1 (0.4) [0] Bronchitis chronic 0 (0.0) [0] 0 (0.0) [0] 2 (0.7) [0] Pharyngitis 2 (0.3) [0] 0 (0.0) [0] 0 (0.0) [0] Dehydration 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Dermatitis atopic 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Drug toxicity 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Ear infection 0 (0.0) [0] 1 (1.1) [0] 0 (0.0) [0] Febrile convulsion 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Gastritis 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Gastroenteritis rotavirus 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Laryngitis 0 (0.0) [0] 1 (1.1) [0] 0 (0.0) [0] Microcytic anaemia 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Nasopharyngitis 0 (0.0) [0] 0 (0.0) [0] 1 (0.4) [0] Oedema peripheral 0 (0.0) [0] 0 (0.0) [0] 1 (0.4) [1] Pneumonia 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Respiratory tract infection 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Upper respiratory tract infection 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Fatal SAEs - Group N = 737 Group N = 92 Group N = 283 Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Safety Results: Number (%) of subjects with (SAEs) within the 31 days after the booster dose (reported in the previous table) and during the extended safety follow-up period (Total vaccinated cohort) All SAEs (from the booster dose up to the end of the extended safety follow-up period) - Group N = 726 Group N = 91 Group N = 282 Subjects with any SAE(s), n (%) [n related] 33 (4.5) [0] 6 (6.6) [0] 8 (2.8) [1] Bronchitis chronic 6 (0.8) [0] 0 (0.0) [0] 4 (1.4) [0] Gastroenteritis 9 (1.2) [0] 0 (0.0) [0] 1 (0.4) [0] Bronchitis 2 (0.3) [0] 1 (1.1) [0] 2 (0.7) [0] Gastroenteritis rotavirus 1 (0.1) [0] 1 (1.1) [0] 1 (0.4) [0] Laryngitis 1 (0.1) [0] 2 (2.2) [0] 0 (0.0) [0] Diarrhoea 1 (0.1) [0] 1 (1.1) [0] 0 (0.0) [0] Febrile convulsion 2 (0.3) [0] 0 (0.0) [0] 0 (0.0) [0] Nasopharyngitis 1 (0.1) [0] 0 (0.0) [0] 1 (0.4) [0] Pharyngitis 2 (0.3) [0] 0 (0.0) [0] 0 (0.0) [0] Pneumonia 2 (0.3) [0] 0 (0.0) [0] 0 (0.0) [0] Respiratory tract infection 1 (0.1) [0] 0 (0.0) [0] 1 (0.4) [0] Adenovirus infection 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Asthma 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Bronchiolitis 0 (0.0) [0] 1 (1.1) [0] 0 (0.0) [0] Concussion 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Dehydration 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Dermatitis atopic 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0]
Drug toxicity 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Ear infection 0 (0.0) [0] 1 (1.1) [0] 0 (0.0) [0] Gastritis 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Limb injury 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Microcytic anaemia 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Oedema peripheral 0 (0.0) [0] 0 (0.0) [0] 1 (0.4) [1] Otitis media 0 (0.0) [0] 0 (0.0) [0] 1 (0.4) [0] Purpura 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Pyelonephritis 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Stomatitis 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Thermal burn 0 (0.0) [0] 1 (1.1) [0] 0 (0.0) [0] Upper respiratory tract infection 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Weight gain poor 1 (0.1) [0] 0 (0.0) [0] 0 (0.0) [0] Fatal SAEs - Group N = 726 Group N = 91 Group N = 282 Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Conclusion: Please refer to the publications section. Date updated: 11 September 2014