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.: 106208 (10PN-PD-DIT-005) Title: A phase II, randomized, controlled study to assess the reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals 10-valent pneumococcal conjugate vaccine, when administered concomitantly with GSK Biologicals combined diphtheria-tetanus- acellular pertussis-hepatitis B-inactivated polio virus/haemophilus influenzae type b vaccine (Infanrix hexa ) as a 3-dose primary immunization course at 2, 4 and 6 months of age. 10Pn-PD-DiT: GlaxoSmithKline (GSK) Biologicals 10-valent pneumococcal conjugate vaccine. Infanrix hexa (DTPa-HBV-IPV/Hib): GSK Biologicals combined diphtheria tetanus acellular pertussis hepatitis B- inactivated polio virus vaccine to be mixed with a lyophilized Haemophilus influenzae type b tetanus conjugate vaccine. Rationale: The aim of this study was to evaluate the safety and immunogenicity of the 10Pn-PD-DiT vaccine, coadministered with DTPa-HBV-IPV/Hib vaccine. Havrix served as control. Havrix (HAV): GSK Biologicals inactivated hepatitis A vaccine. Phase: II Study Period: 04 April 2006 to 30 October 2006 Study Design: Observer-blind, randomized (1:1), controlled study with 2 parallel groups. Centers: 10 study centers in Chile. Indication: Three-dose primary vaccination of healthy infants against Streptococcus pneumonia, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b and hepatitis A. Treatment: The study groups were as follows: 10Pn Group received 10Pn-PD-DiT according to a 3-dose vaccination schedule. HAV Group received HAV vaccine according to a 3-dose vaccination schedule. Both vaccines were administered intramuscularly into the right thigh according to a 3-dose vaccination schedule at 2-4-6 months of age. DTPa-HBV-IPV/Hib vaccine was given concomitantly to both study groups through an intramuscular injection in the left thigh according to the same 3-dose vaccination schedule. To comply with local immunization recommendations licensed oral polio vaccine (OPV) was administered to all subjects at 7 months of age. Objectives: To assess the safety of the 10Pn-PD-DiT vaccine when co-administered with DTPa-HBV-IPV/Hib vaccine in infants at 2-4-6 months of age in terms of the occurrence of adverse events (AEs) with intensity grade 3. Primary Outcome/Efficacy Variable: Occurrence of grade 3 AEs (solicited and/or unsolicited) within 4 days (Day 0-3) after each vaccination. Secondary Outcome/Efficacy Variable(s): Safety Occurrence of solicited local symptoms (any and grade 3) within 4 days (Day 0-3) after each vaccination. Occurrence of solicited general symptoms (any and grade 3) within 4 days (Day 0-3) after each vaccination. Occurrence of unsolicited AEs within 31 days (Day 0-30) after each vaccination. Occurrence of serious adverse events (SAEs) during the whole study period. Immunogenicity Prior to and 1 month after the administration of the 3rd dose of the primary vaccination course with 10Pn-PD-DiT in all subjects: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody concentrations against protein D. Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.20 g/ml. Seropositivity status, defined as: - Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations 0.05 g/ml - Anti-protein D (anti-pd) antibody concentrations 100 EL.U/mL. 1 month after the administration of the 3rd dose of the primary vaccination course with 10Pn-PD-DiT or HAV vaccine, in 50% of subjects in each group: Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Anti-hepatitis A (anti-hav) antibody concentrations. Seropositivity status, defined as: - Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F 8. - Anti-HAV antibody concentrations 15 miu/ml.
Prior to and 1 month after the administration of the 3rd dose of the primary vaccination course with DTPa-HBV-IPV/Hib vaccine in 50% of subjects in each group: Anti-polyribosyl ribitol phosphate (anti-prp), anti-diphtheria and anti-tetanus toxoids, anti-pertussis toxoid (anti-pt), anti-filamentous haemagglutinin (anti-fha), anti-pertactin (anti-prn) antibody concentrations. 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 g/ml & 1.0 g/ml. 1 month after the administration of the 3rd dose of the primary vaccination course with DTPa-HBV-IPV/Hib vaccine in 50% of subjects in each group: Anti-hepatitis B surface antigen (anti-hbs) antibody concentrations and anti-polio type 1, 2 and 3 titers. Seroprotection status, defined as: - 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. Primary vaccine response to PT, FHA and PRN; defined as appearance of antibodies in subjects who were initially seronegative (i.e., with antibody concentrations < 5 EL.U/mL), or at least maintenance of pre-vaccination antibody concentrations in those who were initially seropositive (i.e., with antibody concentrations 5 EL.U/mL). Statistical Methods: The analyses were performed on the Total vaccinated cohort and the according-to-protocol (ATP) cohort for immunogenicity. The Total vaccinated cohort included all subjects who received at least one dose of vaccine. The according-to-protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. Statistical analyses were performed per treatment actually administered. Analysis of safety The analysis of safety was performed on the Total vaccinated cohort. Standardized asymptotic 95% CIs for the difference between groups (10Pn minus HAV), in terms of percentage of subjects with grade 3 AEs (solicited and/or unsolicited) within 4 days (Day 0-3) after at least one vaccination dose, were computed. The percentage of subjects with solicited local or general AEs within the 4-day follow-up period was summarized per dose and across doses with exact 95% confidence interval (CI). The number (percentage) of subjects with unsolicited AEs within the 31-day follow-up period was tabulated according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. SAEs occurring during the study period were reported according to the MedDRA preferred terms. Analysis of immunogenicity The analysis of immunogenicity was performed on the ATP cohort for immunogenicity Geometric mean antibody concentrations/titers (GMCs/GMTs), seropositivity, seroprotection and vaccine response rates (as applicable) were calculated with their 95% CI for each group, each antigen/serotype and at each applicable blood sampling time point. Study Population: Male or female subjects between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination, born after a gestation period of 36 to 42 weeks and free of obvious health problems as established by medical history and clinical examination before entering into the study. Subjects with a previous vaccination against, a history of or intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, hepatitis A and/or Streptococcus pneumoniae diseases were excluded. Written informed consent was obtained from the parent or guardian of the subject prior to study enrolment. Number of subjects 10Pn Group HAV Group Planned, N 120 120 Randomized, N (Total Vaccinated Cohort) 119 121 Completed, n (%) 117 (98.3) 120 (99.2) Total Number Subjects Withdrawn, n (%) 2 (1.7) 1 (0.8) Withdrawn due to Adverse Events n (%) 0 (0) 0 (0)
Withdrawn due to Lack of Efficacy n (%) Not applicable Not applicable Withdrawn for other reasons n (%) 2 (1.7) 1 (0.8) Demographics 10Pn Group HAV Group N (Total Vaccinated Cohort) 119 121 Females:Males 60:59 62:59 Mean Age, weeks (SD) 8.4 (1.25) 8.4 (1.22) White - Caucasian, n (%) 119 (100) 120 (99.2) Primary Efficacy Results: Difference between groups in percentage of subjects reporting a grade 3* solicited /or unsolicited symptom during the 4-day (Day 0-3) post-vaccination period (Total vaccinated cohort) Dose 10Pn Group HAV Group Difference in percentage (10Pn minus HAV) N n % 95% CI N n % 95% CI % 95% CI LL UL Dose 1 119 22 18.5 12.0 26.6 121 7 5.8 2.4 11.6 12.70 4.68 21.33 Dose 2 117 18 15.4 9.4 23.2 120 12 10.0 5.3 16.8 5.38-3.19 14.21 Dose 3 116 12 10.3 5.5 17.4 120 17 14.2 8.5 21.7-3.82-12.47 4.75 Across doses 119 41 34.5 26.0 43.7 121 30 24.8 17.4 33.5 9.66-1.90 21.05 N = number of subjects with at least one documented dose n (%) = number (percentage) of subjects with a specified symptom 95% CI = standardized asymptotic 95% confidence interval, LL = Lower Limit, UL = Upper Limit * Grade 3 unsolicited AEs were defined as unsolicited AEs which prevented normal, everyday activities; for definitions of grade 3 solicited local and general symptoms, please refer to the next 2 tables below. Number (percentage) of subjects with solicited local symptoms reported during the 4-day (Day 0-3) post-vaccination period following each dose and overall (Total vaccinated cohort) Symptom Intensity 10Pn Group HAV Group N n % 95% CI N n % 95% CI Dose 1 Pain Any 119 55 46.2 37.0 55.6 121 45 37.2 28.6 46.4 Grade 3 119 14 11.8 6.6 19.0 121 2 1.7 0.2 5.8 Redness Any 119 36 30.3 22.2 39.3 121 30 24.8 17.4 33.5 > 30 mm 119 2 1.7 0.2 5.9 121 0 0.0 0.0 3.0 Swelling Any 119 30 25.2 17.7 34.0 121 26 21.5 14.5 29.9 > 30 mm 119 3 2.5 0.5 7.2 121 4 3.3 0.9 8.2 Dose 2 Pain Any 117 60 51.3 41.9 60.6 120 42 35.0 26.5 44.2 Grade 3 117 11 9.4 4.8 16.2 120 5 4.2 1.4 9.5 Redness Any 117 48 41.0 32.0 50.5 120 40 33.3 25.0 42.5 > 30 mm 117 0 0.0 0.0 3.1 120 2 1.7 0.2 5.9 Swelling Any 117 44 37.6 28.8 47.0 120 35 29.2 21.2 38.2 > 30 mm 117 3 2.6 0.5 7.3 120 4 3.3 0.9 8.3 Dose 3 Pain Any 116 36 31.0 22.8 40.3 120 31 25.8 18.3 34.6 Grade 3 116 5 4.3 1.4 9.8 120 1 0.8 0.0 4.6 Redness Any 116 42 36.2 27.5 45.6 120 38 31.7 23.5 40.8 > 30 mm 116 1 0.9 0.0 4.7 120 4 3.3 0.9 8.3 Swelling Any 116 35 30.2 22.0 39.4 120 29 24.2 16.8 32.8 > 30 mm 116 3 2.6 0.5 7.4 120 6 5.0 1.9 10.6 Across doses Pain Any 119 80 67.2 58.0 75.6 121 69 57.0 47.7 66.0 Grade 3 119 24 20.2 13.4 28.5 121 8 6.6 2.9 12.6 Redness Any 119 66 55.5 46.1 64.6 121 62 51.2 42.0 60.4
> 30 mm 119 3 2.5 0.5 7.2 121 5 4.1 1.4 9.4 Swelling Any 119 56 47.1 37.8 56.4 121 53 43.8 34.8 53.1 > 30 mm 119 8 6.7 2.9 12.8 121 11 9.1 4.6 15.7 N= number of subjects with at least one documented dose n (%) = number (percentage) of subjects with at least once the symptom whatever the number of injections 95% CI= exact 95% confidence interval; LL = lower limit, UL = upper limit Grade 3 pain= Cried when limb was moved / spontaneously painful Number (percentage) of subjects with solicited general symptoms reported during the 4-day (Day 0-3) post-vaccination period following each dose and overall (Total vaccinated cohort) Symptom Intensity / 10Pn Group HAV Group relationship N n % 95 % CI N n % 95 % CI Dose 1 Drowsiness Any 119 74 62.2 52.8 70.9 121 54 44.6 35.6 53.9 Grade 3 119 1 0.8 0.0 4.6 121 1 0.8 0.0 4.5 Related 119 62 52.1 42.8 61.3 121 46 38.0 29.3 47.3 Fever* 38 C 119 47 39.5 30.7 48.9 121 31 25.6 18.1 34.4 > 40 C 119 0 0.0 0.0 3.1 121 0 0.0 0.0 3.0 Related 119 47 39.5 30.7 48.9 121 31 25.6 18.1 34.4 Irritability Any 119 84 70.6 61.5 78.6 121 74 61.2 51.9 69.9 Grade 3 119 6 5.0 1.9 10.7 121 1 0.8 0.0 4.5 Related 119 82 68.9 59.8 77.1 121 67 55.4 46.1 64.4 Loss of appetite Any 119 47 39.5 30.7 48.9 121 28 23.1 16.0 31.7 Grade 3 119 0 0.0 0.0 3.1 121 0 0.0 0.0 3.0 Related 119 45 37.8 29.1 47.2 121 25 20.7 13.8 29.0 Dose 2 Drowsiness Any 117 52 44.4 35.3 53.9 120 38 31.7 23.5 40.8 Grade 3 117 1 0.9 0.0 4.7 120 0 0.0 0.0 3.0 Related 117 48 41.0 32.0 50.5 120 29 24.2 16.8 32.8 Fever* 38 C 117 49 41.9 32.8 51.4 120 39 32.5 24.2 41.7 > 40 C 117 0 0.0 0.0 3.1 120 0 0.0 0.0 3.0 Related 117 49 41.9 32.8 51.4 120 37 30.8 22.7 39.9 Irritability Any 117 83 70.9 61.8 79.0 120 71 59.2 49.8 68.0 Grade 3 117 9 7.7 3.6 14.1 120 4 3.3 0.9 8.3 Related 117 80 68.4 59.1 76.7 120 65 54.2 44.8 63.3 Loss of appetite Any 117 33 28.2 20.3 37.3 120 29 24.2 16.8 32.8 Grade 3 117 0 0.0 0.0 3.1 120 1 0.8 0.0 4.6 Related 117 30 25.6 18.0 34.5 120 23 19.2 12.6 27.4 Dose 3 Drowsiness Any 116 45 38.8 29.9 48.3 120 23 19.2 12.6 27.4 Grade 3 116 2 1.7 0.2 6.1 120 0 0.0 0.0 3.0 Related 116 38 32.8 24.3 42.1 120 20 16.7 10.5 24.6 Fever* 38 C 116 28 24.1 16.7 33.0 120 16 13.3 7.8 20.7 > 40 C 116 0 0.0 0.0 3.1 120 0 0.0 0.0 3.0 Related 116 23 19.8 13.0 28.3 120 10 8.3 4.1 14.8 Irritability Any 116 62 53.4 44.0 62.8 120 53 44.2 35.1 53.5 Grade 3 116 5 4.3 1.4 9.8 120 4 3.3 0.9 8.3 Related 116 53 45.7 36.4 55.2 120 43 35.8 27.3 45.1 Loss of appetite Any 116 30 25.9 18.2 34.8 120 21 17.5 11.2 25.5 Grade 3 116 1 0.9 0.0 4.7 120 0 0.0 0.0 3.0 Related 116 22 19.0 12.3 27.3 120 16 13.3 7.8 20.7 Across doses Drowsiness Any 119 92 77.3 68.7 84.5 121 72 59.5 50.2 68.3
Grade 3 119 4 3.4 0.9 8.4 121 1 0.8 0.0 4.5 Related 119 79 66.4 57.2 74.8 121 62 51.2 42.0 60.4 Fever* 38 C 119 75 63.0 53.7 71.7 121 60 49.6 40.4 58.8 > 40 C 119 0 0.0 0.0 3.1 121 0 0.0 0.0 3.0 Related 119 74 62.2 52.8 70.9 121 57 47.1 38.0 56.4 Irritability Any 119 103 86.6 79.1 92.1 121 96 79.3 71.0 86.2 Grade 3 119 17 14.3 8.5 21.9 121 7 5.8 2.4 11.6 Related 119 101 84.9 77.2 90.8 121 91 75.2 66.5 82.6 Loss of appetite Any 119 65 54.6 45.2 63.8 121 57 47.1 38.0 56.4 Grade 3 119 1 0.8 0.0 4.6 121 1 0.8 0.0 4.5 Related 119 60 50.4 41.1 59.7 121 49 40.5 31.7 49.8 N= number of subjects with at least one documented dose n (%) = number (percentage) of subjects with at least once the symptom whatever the number of injections 95% CI= exact 95% confidence interval; LL = lower limit, UL = upper limit * Rectal temperature measurements Grade 3 drowsiness = drowsiness that prevented normal everyday activities Grade 3 irritability = crying that could not be comforted Grade 3 loss of appetite = not eating at all Related = symptom considered by the investigator to have a causal relationship to study vaccination Seropositivity rates and GMCs for pneumococcal antibodies (22F-ELISA) against serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ATP cohort for immunogenicity) Antibody Group Timing N 0.05 g/ml 0.2 g/ml GMC (g/ml) n % 95% CI LL UL Anti-1 10Pn PRE 112 49 43.8 34.4 53.4 10 8.9 4.4 15.8 0.05 0.04 0.06 PIII(M5) 117 117 100 96.9 100 117 100 96.9 100 2.40 2.07 2.79 HAV PRE 115 47 40.9 31.8 50.4 12 10.4 5.5 17.5 0.05 0.04 0.06 PIII(M5) 107 14 13.1 7.3 21.0 3 2.8 0.6 8.0 0.03 0.03 0.04 Anti-4 10Pn PRE 112 48 42.9 33.5 52.6 10 8.9 4.4 15.8 0.05 0.04 0.06 PIII(M5) 117 116 99.1 95.3 100 116 99.1 95.3 100 3.43 2.91 4.04 HAV PRE 114 54 47.4 37.9 56.9 16 14.0 8.2 21.8 0.06 0.05 0.07 PIII(M5) 103 6 5.8 2.2 12.2 1 1.0 0.0 5.3 0.03 0.03 0.03 Anti-5 10Pn PRE 110 58 52.7 43.0 62.3 12 10.9 5.8 18.3 0.06 0.05 0.07 PIII(M5) 117 117 100 96.9 100 117 100 96.9 100 3.28 2.86 3.76 HAV PRE 112 52 46.4 37.0 56.1 10 8.9 4.4 15.8 0.05 0.04 0.06 PIII(M5) 106 32 30.2 21.7 39.9 4 3.8 1.0 9.4 0.04 0.03 0.05 Anti-6B 10Pn PRE 111 76 68.5 59.0 77.0 31 27.9 19.8 37.2 0.10 0.08 0.12 PIII(M5) 117 114 97.4 92.7 99.5 109 93.2 87.0 97.0 1.35 1.09 1.67 HAV PRE 114 75 65.8 56.3 74.4 25 21.9 14.7 30.6 0.09 0.07 0.11 PIII(M5) 109 30 27.5 19.4 36.9 5 4.6 1.5 10.4 0.04 0.03 0.04 Anti-7F 10Pn PRE 112 76 67.9 58.4 76.4 33 29.5 21.2 38.8 0.10 0.08 0.13 PIII(M5) 117 117 100 96.9 100 117 100 96.9 100 4.54 3.99 5.16 HAV PRE 114 75 65.8 56.3 74.4 30 26.3 18.5 35.4 0.10 0.08 0.13 PIII(M5) 110 35 31.8 23.3 41.4 6 5.5 2.0 11.5 0.04 0.04 0.05 Anti-9V 10Pn PRE 109 70 64.2 54.5 73.2 27 24.8 17.0 34.0 0.08 0.07 0.10 PIII(M5) 117 117 100 96.9 100 116 99.1 95.3 100 2.85 2.43 3.35 HAV PRE 114 73 64.0 54.5 72.8 26 22.8 15.5 31.6 0.09 0.07 0.11 PIII(M5) 111 13 11.7 6.4 19.2 6 5.4 2.0 11.4 0.03 0.03 0.04 Anti-14 10Pn PRE 108 108 100 96.6 100 89 82.4 73.9 89.1 0.71 0.56 0.91 PIII(M5) 117 117 100 96.9 100 117 100 96.9 100 4.91 4.00 6.03 HAV PRE 112 109 97.3 92.4 99.4 93 83.0 74.8 89.5 0.61 0.49 0.76 PIII(M5) 111 73 65.8 56.2 74.5 26 23.4 15.9 32.4 0.09 0.07 0.11 Anti-18C 10Pn PRE 108 76 70.4 60.8 78.8 43 39.8 30.5 49.7 0.12 0.10 0.16
PIII(M5) 117 116 99.1 95.3 100 116 99.1 95.3 100 6.75 5.56 8.21 HAV PRE 113 77 68.1 58.7 76.6 35 31.0 22.6 40.4 0.11 0.09 0.15 PIII(M5) 105 17 16.2 9.7 24.7 4 3.8 1.0 9.5 0.03 0.03 0.04 Anti-19F 10Pn PRE 110 97 88.2 80.6 93.6 77 70.0 60.5 78.4 0.31 0.24 0.40 PIII(M5) 117 117 100 96.9 100 117 100 96.9 100 10.70 9.28 12.34 HAV PRE 112 103 92.0 85.3 96.3 70 62.5 52.9 71.5 0.28 0.22 0.35 PIII(M5) 109 50 45.9 36.3 55.7 17 15.6 9.4 23.8 0.06 0.05 0.08 Anti-23F 10Pn PRE 109 71 65.1 55.4 74.0 37 33.9 25.1 43.6 0.11 0.08 0.14 PIII(M5) 117 114 97.4 92.7 99.5 110 94.0 88.1 97.6 1.78 1.41 2.25 HAV PRE 114 73 64.0 54.5 72.8 37 32.5 24.0 41.9 0.10 0.08 0.13 PIII(M5) 107 19 17.8 11.0 26.3 4 3.7 1.0 9.3 0.03 0.03 0.04 PRE = before first dose Seropositivity rates and GMCs for anti-pd antibodies (ATP cohort for immunogenicity) Antibody Group Timing N 100 EL.U/mL GMC (EL.U/mL) Anti-PD 10Pn PRE 102 23 22.5 14.9 31.9 72.4 62.6 83.7 PIII(M5) 116 115 99.1 95.3 100 2550.4 2136.1 3045.1 HAV PRE 103 28 27.2 18.9 36.8 75.6 65.1 87.9 PIII(M5) 109 49 45.0 35.4 54.8 106.9 89.0 128.4 PRE = before first dose Seropositivity rates and GMTs for opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, one month after Dose 3 (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT Opsono-1 10Pn PIII(M5) 49 37 75.5 61.1 86.7 79.7 42.6 149.1 HAV PIII(M5) 55 2 3.6 0.4 12.5 4.5 3.8 5.3 Opsono-4 10Pn PIII(M5) 48 48 100 92.6 100 694.1 528.7 911.2 HAV PIII(M5) 54 1 1.9 0.0 9.9 4.1 3.9 4.3 Opsono-5 10Pn PIII(M5) 49 47 95.9 86.0 99.5 162.3 112.4 234.3 HAV PIII(M5) 53 1 1.9 0.0 10.1 4.3 3.7 4.9 Opsono-6B 10Pn PIII(M5) 49 47 95.9 86.0 99.5 801.5 526.8 1219.4 HAV PIII(M5) 49 4 8.2 2.3 19.6 6.1 4.0 9.3 Opsono-7F 10Pn PIII(M5) 48 48 100 92.6 100 3959.8 2858.0 5486.2 HAV PIII(M5) 33 18 54.5 36.4 71.9 89.9 31.5 256.3 Opsono-9V 10Pn PIII(M5) 49 49 100 92.7 100 1360.8 972.6 1903.9 HAV PIII(M5) 49 6 12.2 4.6 24.8 6.4 4.4 9.3 Opsono-14 10Pn PIII(M5) 49 47 95.9 86.0 99.5 801.3 521.4 1231.6 HAV PIII(M5) 44 7 15.9 6.6 30.1 7.8 4.8 12.7 Opsono- 10Pn PIII(M5) 47 46 97.9 88.7 99.9 306.9 226.6 415.7 18C HAV PIII(M5) 32 1 3.1 0.1 16.2 4.2 3.8 4.7 Opsono-19F 10Pn PIII(M5) 47 46 97.9 88.7 99.9 656.5 419.3 1028.1 HAV PIII(M5) 30 0 0.0 0.0 11.6 4.0 4.0 4.0
Opsono-23F 10Pn PIII(M5) 49 47 95.9 86.0 99.5 1181.3 731.5 1907.7 HAV PIII(M5) 51 7 13.7 5.7 26.3 7.3 4.6 11.4 n (%) = number (percentage) of subjects with antibody titer within the specified range Seropositivity rates and GMCs for anti-hav antibodies, one month after Dose 3 (ATP cohort for immunogenicity) Group Timing N 15 miu/ml GMC (miu/ml) 10Pn PIII(M5) 54 44 81.5 68.6 90.7 103.1 66.8 159.1 HAV PIII(M5) 56 56 100 93.6 100 521.7 386.5 704.2 Seropositivity 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) Anti-diphtheria 10Pn PRE 62 2 3.2 0.4 11.2 0.052 0.049 0.054 PIII(M5) 63 63 100 94.3 100 5.695 5.078 6.388 HAV PRE 58 4 6.9 1.9 16.7 0.055 0.050 0.060 PIII(M5) 53 53 100 93.3 100 3.750 3.036 4.632 Anti-tetanus 10Pn PRE 59 11 18.6 9.7 30.9 0.065 0.056 0.077 PIII(M5) 63 63 100 94.3 100 8.654 7.552 9.916 HAV PRE 58 12 20.7 11.2 33.4 0.067 0.057 0.079 PIII(M5) 52 52 100 93.2 100 5.789 4.835 6.931 PRE = before first dose 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) Anti-PT 10Pn PRE 57 15 26.3 15.5 39.7 3.7 3.0 4.4 PIII(M5) 63 63 100 94.3 100 77.8 65.9 91.9 HAV PRE 54 8 14.8 6.6 27.1 3.1 2.7 3.6 PIII(M5) 51 51 100 93.0 100 82.9 70.0 98.2 Anti-FHA 10Pn PRE 57 49 86.0 74.2 93.7 13.9 10.7 18.1 PIII(M5) 63 63 100 94.3 100 308.6 257.7 369.5 HAV PRE 55 44 80.0 67.0 89.6 10.1 7.8 13.2 PIII(M5) 51 51 100 93.0 100 399.1 336.1 473.8 Anti-PRN 10Pn PRE 57 21 36.8 24.4 50.7 4.4 3.5 5.4 PIII(M5) 63 63 100 94.3 100 169.0 141.6 201.7 HAV PRE 55 18 32.7 20.7 46.7 4.0 3.3 5.0 PIII(M5) 51 51 100 93.0 100 234.7 194.2 283.7
PRE = before first dose Seropositivity rates and GMCs for anti-hbs antibodies, one month after Dose 3 (ATP cohort for immunogenicity) Antibody Group Timing N 10 miu/ml GMC (miu/ml) Anti-HBs 10Pn PIII(M5) 63 60 95.2 86.7 99.0 559.1 385.7 810.5 HAV PIII(M5) 58 58 100 93.8 100 895.2 628.2 1275.7 Seropositivity rates and GMTs for anti-polio 1, anti-polio 2 and anti-polio 3 antibodies, one month after Dose 3 (ATP cohort for immunogenicity) Antibody Group Timing N 8 GMT Anti-polio 1 10Pn PIII(M5) 34 34 100 89.7 100 1571.1 1021.6 2416.3 HAV PIII(M5) 33 33 100 89.4 100 1824.8 1158.7 2873.8 Anti-polio 2 10Pn PIII(M5) 31 31 100 88.8 100 640.6 399.8 1026.4 HAV PIII(M5) 27 27 100 87.2 100 1393.4 886.7 2189.8 Anti-polio 3 10Pn PIII(M5) 30 30 100 88.4 100 2194.9 1446.8 3329.9 HAV PIII(M5) 28 27 96.4 81.7 99.9 2496.5 1316.0 4735.8 n (%) = number (percentage) of subjects with antibody titer within the specified range Seropositivity rates and GMCs for anti-prp antibodies (ATP cohort for immunogenicity) Antibody Anti- PRP Group Timing N 0.15 g/ml 1 g/ml GMC (g/ml) n % 95% CI LL UL 10Pn PRE 58 21 36.2 24.0 49.9 3 5.2 1.1 14.4 0.133 0.105 0.168 PIII(M5) 63 63 100 94.3 100 63 100 94.3 100 13.835 10.918 17.532 HAV PRE 58 29 50.0 36.6 63.4 2 3.4 0.4 11.9 0.178 0.135 0.234 PIII(M5) 56 56 100 93.6 100 52 92.9 82.7 98.0 10.488 7.384 14.899 PRE = before first dose Vaccine response to PT, FHA and PRN, one month after Dose 3 (ATP cohort for immunogenicity) Antibody Group Pre-vaccination status N Vaccine Response n % 95% CI LL UL Anti-PT 10Pn S- 42 42 100 91.6 100 S+ 15 14 93.3 68.1 99.8 Total 57 56 98.2 90.6 100 HAV S- 40 40 100 91.2 100 S+ 8 8 100 63.1 100 Total 48 48 100 92.6 100 Anti-FHA 10Pn S- 8 8 100 63.1 100 S+ 49 48 98.0 89.1 99.9
Total 57 56 98.2 90.6 100 HAV S- 10 10 100 69.2 100 S+ 38 38 100 90.7 100 Total 48 48 100 92.6 100 Anti-PRN 10Pn S- 36 36 100 90.3 100 S+ 21 21 100 83.9 100 Total 57 57 100 93.7 100 HAV S- 34 34 100 89.7 100 S+ 14 14 100 76.8 100 Total 48 48 100 92.6 100 S- = seronegative subjects (antibody concentration < 5 EL.U/mL) prior to vaccination S+ = seropositive subjects (antibody concentration 5 EL.U/mL) prior to vaccination Total = subjects either seropositive or seronegative at pre-vaccination N = number of subjects with both pre- and post-vaccination results available n (%) = number (percentage) of responders Vaccine response defined as: For initially seronegative subjects, antibody concentration 5 EL.U/mL at PIII(M5) For initially seropositive subjects, antibody concentration at PIII(M5) pre-vaccination antibody concentration 95% CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Safety Results: Number (%) of subjects with adverse events (Total vaccinated cohort) Most frequent adverse events - On-Therapy (occurring within Day 0-30 following vaccination) 10Pn Group N = 119 HAV Group N = 121 Subjects with any AE(s), n (%) 104 (87.4) 101 (83.5) Bronchitis 46 (38.7) 49 (40.5) Nasopharyngitis 30 (25.2) 27 (22.3) Upper respiratory tract infection 21 (17.6) 20 (16.5) Injection site induration 18 (15.1) 16 (13.2) Abdominal pain 13 (10.9) 4 (3.3) Pharyngitis 5 (4.2) 11 (9.1) Conjunctivitis 5 (4.2) 10 (8.3) Diarrhoea 4 (3.4) 8 (6.6) Nasal congestion 6 (5.0) 6 (5.0) Gastrooesophageal reflux disease 2 (1.7) 9 (7.4) Cough 6 (5.0) 4 (3.3) Pyrexia 3 (2.5) 7 (5.8) Vomiting 3 (2.5) 6 (5.0) Unsolicited AEs counting rule: > 30 subjects per treatment group and <= 3 groups, display the most frequent 10 events in each group Safety Results: Number (%) of subjects with serious adverse events (Total vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs 10Pn Group N = 119 HAV Group N = 121 Subjects with any SAE(s), n (%) [n related] 8 (6.7) [0] 8 (6.6) [0] Bronchiolitis 2 (1.7) [0] 3 (2.5) [0] Pneumonia 1 (0.8) [0] 3 (2.5) [0] Pneumonia respiratory syncytial viral 1 (0.8) [0] 3 (2.5) [0] Bronchitis 0 (0.0) [0] 1 (0.8) [0] Bronchopneumonia 1 (0.8) [0] 0 (0.0) [0] Gastroenteritis rotavirus 1 (0.8) [0] 0 (0.0) [0] Interstitial lung disease 0 (0.0) [0] 1 (0.8) [0] Otitis media acute 0 (0.0) [0] 1 (0.8) [0] Pertussis 1 (0.8) [0] 0 (0.0) [0] Pneumonia parainfluenzae viral 0 (0.0) [0] 1 (0.8) [0] Pyelonephritis acute 1 (0.8) [0] 0 (0.0) [0]
Respiratory failure 1 (0.8) [0] 0 (0.0) [0] Respiratory syncytial virus infection 1 (0.8) [0] 0 (0.0) [0] Fatal SAEs 10Pn Group N = 119 HAV Group N = 121 Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] Conclusion: Across doses, at least one grade 3 solicited or unsolicited symptom was reported during the 4-day follow-up period after vaccination for 41 (34.5%) and 30 (24.8%) subjects in the 10Pn Group and the HAV Group, respectively. At least one unsolicited AE was reported for 104 (87.4%) and 101 (83.5%) subjects in the 10Pn Group and the HAV Group, respectively. SAEs were reported for 8 subjects in each group. None of these SAEs were considered by the investigators to be related to the study vaccination. No fatal SAEs were reported. Please also refer to the publications below. Date updated: 05 August 2013