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.: 792014/001 (-TT-001) Title: A phase II, open (partially double-blind), randomised, controlled, multicentre, primary vaccination study to evaluate the immunogenicity (including immune memory), reactogenicity and safety of three different formulations of the GSK Biologicals combined Haemophilus influenzae type b-meningococcal serogroups CY conjugate vaccine given concomitantly with Infanrix penta and Prevenar, versus ActHIB and Meningitec # given concomitantly with Infanrix penta and versus ActHIB given concomitantly with Infanrix penta and Prevenar in infants according to a 2-4-6 month schedule. # Menjugate was used in this clinical trial instead of Meningitec. This was in line with the protocol amendment that allowed for the administration of Menjugate vaccine in the event of unavailability of Meningitec. HibMenCY (3 different vaccine formulations): GlaxoSmithKline (GSK) Biologicals Haemophilus influenzae type b- meningococcal serogroups C and Y - tetanus toxoid conjugate vaccine. Infanrix penta (DTPa-HBV-IPV): GSK Biologicals combined diphtheria, tetanus, acellular pertussis, hepatitis B and inactivated poliovirus vaccine. Prevenar (7Pn): Pfizer s (formerly Wyeth) pneumococcal 7-valent conjugate vaccine. ActHIB (Hib): Sanofi Pasteurs polyribosyl-ribitol-phosphate (PRP)-tetanus toxoid conjugate vaccine. Menjugate (MenC): Novartis (formerly Chiron) meningococcal C CRM197 conjugate vaccine. Rationale: The purpose of this study was to evaluate the immunogenicity and safety of a primary vaccination course with three different formulations of the candidate HibMenCY vaccine using tetanus toxoid as carrier protein administered concomitantly with DTPa-HBV-IPV and 7Pn. Licensed MenC and Hib conjugate vaccines administered concomitantly with DTPa-HBV-IPV were used as control vaccines. Note: This study was conducted in 2 parts: the primary vaccination phase -TT-001(792014/001) and the immune memory phase -TT-002 (792014/002) This CTRS presents the results of the primary vaccination phase. Phase: II Study Period:18 March 2003 to 12 February 2004 Study Design: Open (partially double-blind for,, and groups), randomised (1:1:1:1:1), controlled, multicentre study with five parallel groups. Centres: Three centres in Australia Indication: Primary immunization of healthy infants in the first year of life against H. influenzae type b and Neisseria meningitidis serogroup C and Y, diphtheria, tetanus, pertussis, hepatitis B, poliovirus and pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, 23F diseases. Treatment: The study groups were as follows: : Subjects received (formulation 1) + DTPa-HBV-IPV + 7Pn : Subjects received (formulation 2) + DTPa-HBV-IPV + 7Pn : Subjects received (formulation 3) + DTPa-HBV-IPV + 7Pn MenC (control): Subject received MenC + Hib + DTPa-HBV-IPV Hib (control): Subjects received Hib + DTPa-HBV-IPV + 7Pn The vaccines were administered intramuscularly as a 3-dose primary vaccination course at 2, 4 and 6 months of age, coadministered with and Hib vaccines in the left thigh, DTPa-HBV-IPV vaccine in the right upper thigh and 7Pn and MenC vaccines in the right lower thigh. Objectives: Only objectives related to the primary phase (792014/001) are presented. To evaluate the non-inferiority of at least one of the 3 formulations of vaccine compared to Hib vaccine (all co-administered with DTPa-HBV-IPV and 7Pn vaccines) in terms of the percentage of subjects with anti-polyribosyl ribitol phosphate (PRP) antibody concentrations 1 µg/ml one month after the third dose of a 3-dose primary vaccination course. To evaluate the immune response to N. meningitidis serogroups C and Y in terms of the number of subjects with serum bactericidal activity using baby rabbit complement (rsba)-menc/rsba-meny titres 1:8 after the third dose of a 3-dose primary vaccination course of each of the three formulations of the vaccine (co-administered with DTPa-HBV-IPV and 7Pn vaccines) using MenC vaccine (co-administered with Hib and DTPa-HBV-IPV vaccines) as control for the immune response to N. meningitidis serogroup C. Primary Outcome/Efficacy Variable: Only outcome measures related to the primary phase (792014/001) are presented. Immunogenicity one month after primary vaccination:
Anti-PRP antibody concentrations 1 g/ml MenC rsba titres 1:8 MenY rsba titres 1:8 Secondary Outcome/Efficacy Variable(s): Only outcome measures related to the primary phase (792014/001) are presented. Immunogenicity prior to vaccination, one month after the third dose of the 3-dose primary vaccination course: rsba-menc and rsba-meny titres rsba-menc 1:8 (except one month post primary vaccination, see primary outcome measure) rsba-meny 1:8 (except one month post primary vaccination, see primary outcome measure) Anti-polysaccharide C (PSC), anti-polysaccharide Y (PSY) concentration Anti-PSC 0.30 g/ml Anti-PSY 0.30 g/ml Anti-PRP concentration Anti-PRP 0.15 g/ml and 1 g/ml (except one month after primary vaccination, see primary outcome measure) Anti-diphtheria, anti-tetanus, anti-filamentus haemagglutinin (FHA), anti-pertactin (PRN), anti-pertussis toxoid (PT), antihepatitis B (HBs), anti-poliovirus 1,2,3, anti-pneumococcal antibodies concentration/titres Seroprotection status against diphtheria, tetanus, poliovirus 1,2,3, or hepatitis B Seroprotection status is defined as: - Anti-diphtheria/anti-tetanus toxoid antibody concentration 0.1IU/ ml - Anti-poliovirus 1, 2 and 3 antibody titres 1:8 - Anti-HBs antibody titre 10 miu/ ml Seropositivity against PRN, FHA or PT. Seropositivity is defined as: - Anti-PRN, anti-pt, anti-fha antibody concentration 5 EL.U/ ml Anti-pneumococcal antibodies 0.05 g/ ml, 0.2 g /ml Safety after each vaccine dose: Occurrence of solicited symptoms (during the 8-day [Day 0-7] follow-up period after each dose) Occurrence of unsolicited symptoms (during the 31-day [Day 0-30] follow-up period after each dose) Safety over the full course of the study (i.e. up to one month post-dose 3): Occurrence of serious adverse events (SAEs) Statistical Methods: The analyses were conducted on the Total Vaccinated cohort and the According to Protocol (ATP) cohort for immunogenicity. - The Total Vaccinated cohort included all subjects with study vaccine administered. - The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, and with no elimination criteria during the study) for whom assay results were available for antibodies against at least one study vaccine antigen component, for at least one blood sample during the primary vaccination course. Analysis of Immunogenicity: The analysis of immunogenicity was performed on the ATP cohort for immunogenicity. The evaluation of the non-inferiority objective for Hib was performed by looking at the standardized asymptotic 95% confidence interval (CI) on the difference between the Hib control group and each of the three groups in the percentage of subjects with anti-prp concentration 1.0 g/ml. No limit of non-inferiority was defined since the purpose of the study was to select the optimal HibMenCY formulation for further development. The evaluation of the immune response to MenC versus the MenC control group was performed by computing the standardized asymptotic 95% CI on the difference between the MenC control group and each of the three groups in the percentage of subjects with rsba-menc titre 1:8. Since there was no control group for MenY, the immune response to MenY was evaluated by computing the exact 95% CI on the percentage of subjects with rsba-meny titre 1:8 in each of the three groups. Geometric mean concentrations/titres (GMCs/Ts) and seroconversion, seroprotection and seropositivity rates were calculated with their 95% CI for each antibody measured at each blood sampling time point. Analysis of safety Analysis of safety was performed on the Total Vaccinated cohort.
For each solicited local and general symptom, the percentage of subjects with the symptom and their exact 95% CI was summarized by vaccine group, by dose and across doses during the 8-day (Days 0-7) follow-up period. The same tabulation was performed for grade 3 symptoms and for general symptoms assessed by the investigator as related to vaccination. The percentage of subjects reporting unsolicited symptoms within the 31-day (Days 0-30) following vaccination was summarized by vaccine group according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred term. SAEs reported over the full course of the study (i.e. up to the post dose 3 visit) and classified by the MedDRA preferred terms were tabulated. Study Population: Healthy male and female infants between, and including, 6 to 12 weeks of age at the time of the first vaccination. Free of obvious health problems, born after a gestation period of 36-42 weeks and vaccinated against hepatitis B at birth. Subjects with history of or known exposure to diphtheria, tetanus, pertussis, poliovirus, or invasive diseases due to N. meningitidis of serogroups C and Y, H. influenzae type b or Streptococcus pneumoniae, and/or previous vaccination against these diseases were excluded. Number of subjects MenC Hib Planned, N 80 80 80 80 80 Randomised, N (Total Vaccinated cohort) 82 82 80 81 82 Completed, n (%) 80 (97.6) 81 (98.8) 78 (97.5) 81 (100) 78 (95.1) Total Number Subjects Withdrawn, n (%) 2 (2.4) 1 (1.2) 2 (2.5) 0 (0.0) 4 (4.9) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 1 (1.3) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not applicable Not applicable Not applicable Not applicable Not applicable Withdrawn for other reasons, n (%) 2 (2.4) 1 (1.2) 1 (1.3) 0 (0.0) 4 (4.9) Demographics MenC Hib N (Total Vaccinated Cohort) 82 82 80 81 82 Females:Males 38:44 45:37 41:39 43:38 37:45 Mean Age, weeks (SD) 8.1 (1.39) 8.3 (1.46) 8.2 (1.65) 8.0 (1.65) 8.1 (1.43) Caucasian, n (%) 82 (100) 77 (93.9) 75 (93.8) 78 (96.3) 80 (97.6) Primary Efficacy Results: Difference between each of the three groups and the Hib group in terms of percentage of subjects with anti-prp concentration 1 µg/ml one month after the third vaccine dose (ATP cohort for Difference between groups: Value 95% CI % LL UL Hib minus -2.7-10.8 4.6 Hib minus -4.1-12.0 2.3 Hib minus 1.7-7.0 11.0 % = percentage of subjects with anti-prp concentration 1 g/ml 95% CI, LL, UL = 95% standardized asymptotic confidence interval, lower and upper limits Primary Efficacy Results: Difference between each of the three groups and the control group in terms of percentage of subjects with rsba-menc titre 1:8 dilution one month after the third vaccine dose (ATP cohort for Difference between groups: Value 95% CI % LL UL MenC minus 0.0-4.9 5.3 MenC minus 0.0-4.9 4.8 MenC minus 0.0-4.9 5.1 % = percentage of subjects with rsba-menc titre 1:8 95% CI; LL, UL = 95% standardized asymptotic confidence interval, lower and upper limits Primary Efficacy Results: Difference between each pair of groups in terms of percentage of subjects with rsba- MenY titre 1:8 one month after the third dose (ATP cohort for Difference between groups: Value 95% CI % LL UL minus 1.5-3.9 8.0 minus 0.0-6.4 6.7 minus -1.4-7.8 3.9 % = percentage of subjects with rsba-meny titre 1:8
95% CI; LL, UL = 95% standardized asymptotic confidence interval, lower and upper limits Primary Efficacy Results: Immunological response one month post dose 3 (ATP cohort for s (Study Month 5) Anti-PRP 1 g/ml rsba-menc 1:8 rsba-meny 1:8 N % 95% CI N % 95% CI N % 95% CI LL UL Hib MenCY 74 97.3 90.6 99.7 69 100.0 94.8 100.0 67 98.5 92.0 100.0 Hib MenCY 76 98.7 92.9 100.0 76 100.0 95.3 100.0 68 100.0 94.7 100.0 Hib MenCY 70 92.9 84.1 97.6 72 100.0 95.3 100.0 69 98.6 92.2 100.0 MenC 74 89.2 79.8 95.2 74 100.0 95.1 100.0 68 14.7 7.3 25.4 Hib 74 94.6 86.7 98.5 76 1.3 0.0 7.1 74 16.2 8.7 26.6 N=number of subjects with available results. % = percentage of subjects with concentration/titre within the specified range. Secondary Outcome Variable(s): Percentage of subjects with anti-prp antibody concentration 0.15 µg/ml, 1.0 µg/ml and GMCs (ATP cohort for Timing N 0.15 g/ml 1 g/ml GMC ( g/ml) n % 95% CI LL UL PRE 68 29 42.6 30.7 55.2 7 10.3 4.2 20.1 0.152 0.120 0.194 PIII(M5) 74 74 100.0 95.1 100.0 72 97.3 90.6 99.7 6.441 5.315 7.805 PRE 70 37 52.9 40.6 64.9 10 14.3 7.1 24.7 0.224 0.164 0.305 PIII(M5) 76 76 100.0 95.3 100.0 75 98.7 92.9 100.0 7.324 5.877 9.127 PRE 67 41 61.2 48.5 72.9 6 9.0 3.4 18.5 0.214 0.166 0.276 PIII(M5) 70 70 100.0 94.9 100.0 65 92.9 84.1 97.6 5.577 4.375 7.110 MenC PRE 67 32 47.8 35.4 60.3 6 9.0 3.4 18.5 0.172 0.132 0.223 PIII(M5) 74 73 98.6 92.7 100.0 66 89.2 79.8 95.2 4.465 3.399 5.865 Hib PRE 73 37 50.7 38.7 62.6 8 11.0 4.9 20.5 0.201 0.153 0.265 PIII(M5) 74 74 100.0 95.1 100.0 70 94.6 86.7 98.5 5.714 4.538 7.195 Secondary Outcome Variable(s): Percentage of subjects with rsba-menc titres 1:8 and GMTs (ATP cohort for Timing N 1:8 GMT PRE 68 2 2.9 0.4 10.2 4.3 3.9 4.7 PIII(M5) 69 69 100.0 94.8 100.0 1293.1 1027.7 1627.1 PRE 66 6 9.1 3.4 18.7 5.2 4.1 6.6 PIII(M5) 76 76 100.0 95.3 100.0 1065.6 858.8 1322.3 PRE 63 2 3.2 0.4 11.0 4.2 3.9 4.6 PIII(M5) 72 72 100.0 95.0 100.0 968.4 770.8 1216.6 MenC PRE 66 3 4.5 0.9 12.7 4.2 4.0 4.5 PIII(M5) 74 74 100.0 95.1 100.0 1931.9 1541.2 2421.6 Hib PRE 70 1 1.4 0.0 7.7 4.1 3.9 4.4 PIII(M5) 76 1 1.3 0.0 7.1 4.2 3.8 4.5 n/% = number/percentage of subjects with titre within the specified range GMT: Geometric mean antibody titre
Secondary Outcome Variable(s): Percentage of subjects with anti-psc antibody concentration 0.3µg/mL and GMCs (ATP cohort for Timing N 0.30 g/ml GMC ( g/ml) PRE 54 5 9.3 3.1 20.3 0.17 0.15 0.20 PIII(M5) 63 63 100.0 94.3 100.0 12.02 9.90 14.59 PRE 54 5 9.3 3.1 20.3 0.17 0.15 0.18 PIII(M5) 65 65 100.0 94.5 100.0 12.09 10.59 13.81 PRE 49 6 12.2 4.6 24.8 0.17 0.15 0.19 PIII(M5) 61 61 100.0 94.1 100.0 9.95 8.34 11.87 MenC PRE 56 5 8.9 3.0 19.6 0.17 0.15 0.20 PIII(M5) 62 62 100.0 94.2 100.0 15.36 12.67 18.62 Hib PRE 56 4 7.1 2.0 17.3 0.17 0.15 0.19 PIII(M5) 63 1 1.6 0.0 8.5 0.15 0.15 0.16 Secondary Outcome Variable(s): Percentage of subjects with rsba-meny antibody titre 1:8 and GMTs (ATP cohort for Timing N 1:8 GMT PRE 68 4 5.9 1.6 14.4 4.6 4.0 5.4 PIII(M5) 67 66 98.5 92.0 100.0 843.5 640.1 1111.7 PRE 65 7 10.8 4.4 20.9 5.6 4.3 7.2 PIII(M5) 68 68 100.0 94.7 100.0 1020.0 790.0 1316.8 PRE 58 5 8.6 2.9 19.0 5.1 4.1 6.3 PIII(M5) 69 68 98.6 92.2 100.0 741.8 538.0 1022.9 MenC PRE 63 9 14.3 6.7 25.4 6.3 4.7 8.4 PIII(M5) 68 10 14.7 7.3 25.4 6.9 5.0 9.5 Hib PRE 66 4 6.1 1.7 14.8 4.9 4.0 5.9 PIII(M5) 74 12 16.2 8.7 26.6 7.3 5.2 10.1 n/% = number/percentage of subjects with titre within the specified range GMT: Geometric mean antibody titre Secondary Outcome Variable(s): Percentage of subjects with anti-psy antibody concentration 0.3µg/mL and GMCs (ATP cohort for Timing N 0.30 g/ml GMC ( g/ml) PRE 51 3 5.9 1.2 16.2 0.17 0.15 0.19 PIII(M5) 67 67 100.0 94.6 100.0 19.22 15.42 23.95 PRE 51 4 7.8 2.2 18.9 0.18 0.15 0.23 PIII(M5) 70 70 100.0 94.9 100.0 19.09 15.44 23.59 PRE 47 3 6.4 1.3 17.5 0.17 0.15 0.19 PIII(M5) 72 72 100.0 95.0 100.0 15.83 12.64 19.82 MenC PRE 56 7 12.5 5.2 24.1 0.20 0.16 0.26
PIII(M5) 66 2 3.0 0.4 10.5 0.16 0.15 0.17 Hib PRE 54 7 13.0 5.4 24.9 0.19 0.16 0.23 PIII(M5) 69 0 0.0 0.0 5.2 0.15 0.15 0.15 Secondary Outcome Variable(s): Seroprotection rates and GMCs for anti-diphtheria antibody concentrations (ATP cohort for Timing N 0.1 IU/mL GMC (IU/mL) PRE 68 26 38.2 26.7 50.8 0.090 0.074 0.110 PIII(M5) 74 74 100.0 95.1 100.0 1.721 1.480 2.003 PRE 70 28 40.0 28.5 52.4 0.098 0.077 0.123 PIII(M5) 76 76 100.0 95.3 100.0 1.797 1.508 2.141 PRE 65 28 43.1 30.8 56.0 0.101 0.080 0.127 PIII(M5) 74 74 100.0 95.1 100.0 2.000 1.706 2.346 MenC PRE 69 26 37.7 26.3 50.2 0.090 0.074 0.110 PIII(M5) 77 77 100.0 95.3 100.0 1.845 1.598 2.130 Hib PRE 74 29 39.2 28.0 51.2 0.093 0.074 0.117 PIII(M5) 76 76 100.0 95.3 100.0 1.970 1.760 2.206 Secondary Outcome Variable(s): Seroprotection rates and GMCs for anti-tetanus antibody concentrations (ATP cohort for Timing N 0.1 IU/mL GMC (IU/mL) PRE 62 54 87.1 76.1 94.3 0.460 0.343 0.617 PIII(M5) 74 74 100.0 95.1 100.0 3.301 2.909 3.747 PRE 64 58 90.6 80.7 96.5 0.470 0.364 0.608 PIII(M5) 76 76 100.0 95.3 100.0 3.816 3.340 4.360 PRE 60 57 95.0 86.1 99.0 0.501 0.386 0.651 PIII(M5) 74 74 100.0 95.1 100.0 3.366 2.974 3.810 MenC PRE 60 57 95.0 86.1 99.0 0.562 0.435 0.727 PIII(M5) 77 77 100.0 95.3 100.0 1.877 1.603 2.197 Hib PRE 68 62 91.2 81.8 96.7 0.533 0.403 0.705 PIII(M5) 76 76 100.0 95.3 100.0 2.033 1.773 2.330 Secondary Outcome Variable(s): Seropositivity rates and GMCs for anti-pt, anti-fha and anti-prn antibody concentrations (ATP cohort for Antibody Timing N 5 EL.U/mL GMC (EL.U/mL)
Anti-PT PRE 65 5 7.7 2.5 17.0 2.7 2.5 2.9 PIII(M5) 74 74 100.0 95.1 100.0 55.1 48.4 62.8 PRE 66 6 9.1 3.4 18.7 2.7 2.5 2.9 PIII(M5) 76 76 100.0 95.3 100.0 55.2 47.9 63.6 PRE 65 5 7.7 2.5 17.0 2.8 2.5 3.1 PIII(M5) 74 74 100.0 95.1 100.0 53.7 46.1 62.5 MenC PRE 63 11 17.5 9.1 29.1 3.1 2.7 3.5 PIII(M5) 77 77 100.0 95.3 100.0 49.7 43.2 57.2 Hib PRE 74 3 4.1 0.8 11.4 2.7 2.4 2.9 PIII(M5) 76 76 100.0 95.3 100.0 54.8 47.3 63.5 Anti-FHA PRE 64 34 53.1 40.2 65.7 5.1 4.2 6.2 PIII(M5) 74 74 100.0 95.1 100.0 137.2 116.4 161.7 PRE 69 28 40.6 28.9 53.1 4.6 3.7 5.7 PIII(M5) 76 76 100.0 95.3 100.0 141.5 122.1 163.9 PRE 65 38 58.5 45.6 70.6 5.8 4.8 7.1 PIII(M5) 74 74 100.0 95.1 100.0 136.2 118.0 157.2 MenC PRE 67 44 65.7 53.1 76.8 7.4 5.8 9.5 PIII(M5) 77 77 100.0 95.3 100.0 132.1 114.1 153.0 Hib PRE 70 31 44.3 32.4 56.7 4.8 3.9 5.9 PIII(M5) 76 76 100.0 95.3 100.0 146.7 124.8 172.4 Anti-PRN PRE 67 20 29.9 19.3 42.3 3.9 3.2 4.7 PIII(M5) 74 74 100.0 95.1 100.0 128.3 107.4 153.1 PRE 63 26 41.3 29.0 54.4 4.7 3.7 5.8 PIII(M5) 76 76 100.0 95.3 100.0 120.7 98.6 147.7 PRE 67 25 37.3 25.8 50.0 4.6 3.7 5.7 PIII(M5) 74 74 100.0 95.1 100.0 106.2 89.3 126.3 MenC PRE 68 30 44.1 32.1 56.7 5.3 4.1 6.8 PIII(M5) 77 76 98.7 93.0 100.0 112.9 91.6 139.1 Hib PRE 71 26 36.6 25.5 48.9 4.4 3.6 5.4 PIII(M5) 76 76 100.0 95.3 100.0 137.8 118.2 160.7 Secondary Outcome Variable(s): Seroprotection rates and GMCs for anti-hbs antibody concentrations (ATP cohort for Timing N 10 miu/ml GMC (miu/ml) PRE 57 15 26.3 15.5 39.7 13.7 8.1 23.1 PIII(M5) 72 71 98.6 92.5 100.0 1769.2 1276.4 2452.2 PRE 55 16 29.1 17.6 42.9 12.2 7.8 19.2 PIII(M5) 74 74 100.0 95.1 100.0 1840.7 1467.3 2309.0 PRE 56 12 21.4 11.6 34.4 10.0 6.9 14.5 PIII(M5) 74 74 100.0 95.1 100.0 1652.6 1301.2 2098.8 MenC PRE 52 14 26.9 15.6 41.0 10.1 7.1 14.4 PIII(M5) 76 76 100.0 95.3 100.0 1752.2 1373.3 2235.6 Hib PRE 57 22 38.6 26.0 52.4 18.8 11.1 32.0 PIII(M5) 75 74 98.7 92.8 100.0 1609.7 1191.1 2175.5
Secondary Outcome Variable(s): Seroprotection rates and GMTs for anti-poliovirus type 1, anti-poliovirus type 2 and antipoliovirus type 3 antibody titres (ATP cohort for Antibody Timing N 1:8 GMT Antipoliovirus type 1 Antipoliovirus type 2 Antipoliovirus type 3 PRE 56 45 80.4 67.6 89.8 36.7 24.6 54.8 PIII(M5) 62 62 100.0 94.2 100.0 669.6 507.5 883.4 PRE 58 50 86.2 74.6 93.9 33.3 23.2 47.6 PIII(M5) 68 68 100.0 94.7 100.0 476.8 364.0 624.4 PRE 50 44 88.0 75.7 95.5 32.9 21.7 49.7 PIII(M5) 66 66 100.0 94.6 100.0 574.7 436.2 757.1 MenC PRE 56 49 87.5 75.9 94.8 52.3 34.9 78.2 PIII(M5) 66 66 100.0 94.6 100.0 454.0 337.5 610.7 Hib PRE 52 45 86.5 74.2 94.4 36.6 24.6 54.3 PIII(M5) 65 65 100.0 94.5 100.0 517.6 396.9 674.9 PRE 56 42 75.0 61.6 85.6 14.9 11.2 19.9 PIII(M5) 59 59 100.0 93.9 100.0 533.8 393.3 724.4 PRE 59 40 67.8 54.4 79.4 13.8 10.3 18.3 PIII(M5) 66 66 100.0 94.6 100.0 369.8 273.4 500.0 PRE 50 36 72.0 57.5 83.8 15.9 11.4 22.1 PIII(M5) 64 64 100.0 94.4 100.0 408.0 297.6 559.4 MenC PRE 55 44 80.0 67.0 89.6 17.2 12.8 23.3 PIII(M5) 66 66 100.0 94.6 100.0 348.9 265.3 458.8 Hib PRE 52 43 82.7 69.7 91.8 17.1 12.7 23.0 PIII(M5) 64 63 98.4 91.6 100.0 368.0 264.0 512.9 PRE 56 20 35.7 23.4 49.6 6.4 5.3 7.8 PIII(M5) 62 62 100.0 94.2 100.0 1266.3 992.1 1616.2 PRE 59 20 33.9 22.1 47.4 6.6 5.2 8.3 PIII(M5) 68 68 100.0 94.7 100.0 1034.8 778.8 1374.8 PRE 50 24 48.0 33.7 62.6 7.9 6.2 10.1 PIII(M5) 66 65 98.5 91.8 100.0 1062.2 809.2 1394.2 MenC PRE 56 22 39.3 26.5 53.2 7.7 5.8 10.1 PIII(M5) 66 65 98.5 91.8 100.0 1084.9 804.2 1463.7 Hib PRE 52 21 40.4 27.0 54.9 8.0 6.1 10.5 PIII(M5) 65 65 100.0 94.5 100.0 945.5 695.9 1284.5 n/% = number/percentage of subjects with titre within the specified range GMT = geometric mean antibody titre Secondary Outcome Variable(s): Percentage of subjects with anti-pneumococcal antibody concentration 0.05µg/mL, 0.2µg/mL and GMCs for anti-4, anti-6b, anti-9v, anti-14, anti-18c, anti-19f and anti-23f serotypes (ATP cohort for Antibody Timing N 0.05 g/ml 0.2 g/ml GMC ( g/ml) n % 95% CI LL UL Anti-4 PRE 44 10 22.7 11.5 37.8 3 6.8 1.4 18.7 0.036 0.029 0.046 PIII(M5) 69 69 100.0 94.8 100.0 69 100.0 94.8 100.0 2.101 1.780 2.480
Anti-6B Anti-9V Anti-14 Anti-18C Anti-19F PRE 43 9 20.9 10.0 36.0 1 2.3 0.1 12.3 0.035 0.028 0.043 PIII(M5) 70 70 100.0 94.9 100.0 70 100.0 94.9 100.0 2.049 1.718 2.442 PRE 39 10 25.6 13.0 42.1 3 7.7 1.6 20.9 0.040 0.030 0.053 PIII(M5) 69 69 100.0 94.8 100.0 69 100.0 94.8 100.0 2.023 1.729 2.366 MenC PRE 51 11 21.6 11.3 35.3 1 2.0 0.0 10.4 0.034 0.028 0.040 PIII(M5) 58 2 3.4 0.4 11.9 1 1.7 0.0 9.2 0.027 0.024 0.030 Hib PRE 46 10 21.7 10.9 36.4 2 4.3 0.5 14.8 0.036 0.029 0.046 PIII(M5) 66 66 100.0 94.6 100.0 66 100.0 94.6 100.0 2.062 1.787 2.380 PRE 44 18 40.9 26.3 56.8 6 13.6 5.2 27.4 0.055 0.039 0.078 PIII(M5) 68 65 95.6 87.6 99.1 58 85.3 74.6 92.7 1.060 0.744 1.511 PRE 41 21 51.2 35.1 67.1 11 26.8 14.2 42.9 0.080 0.052 0.123 PIII(M5) 70 69 98.6 92.3 100.0 64 91.4 82.3 96.8 1.079 0.808 1.442 PRE 39 20 51.3 34.8 67.6 7 17.9 7.5 33.5 0.067 0.046 0.099 PIII(M5) 69 61 88.4 78.4 94.9 56 81.2 69.9 89.6 0.834 0.567 1.225 MenC PRE 49 25 51.0 36.3 65.6 9 18.4 8.8 32.0 0.070 0.049 0.101 PIII(M5) 63 3 4.8 1.0 13.3 1 1.6 0.0 8.5 0.027 0.025 0.030 Hib PRE 49 23 46.9 32.5 61.7 8 16.3 7.3 29.7 0.067 0.045 0.099 PIII(M5) 65 60 92.3 83.0 97.5 56 86.2 75.3 93.5 0.879 0.604 1.278 PRE 46 19 41.3 27.0 56.8 9 19.6 9.4 33.9 0.058 0.040 0.085 PIII(M5) 68 68 100.0 94.7 100.0 68 100.0 94.7 100.0 3.102 2.563 3.754 PRE 42 22 52.4 36.4 68.0 6 14.3 5.4 28.5 0.065 0.044 0.096 PIII(M5) 71 70 98.6 92.4 100.0 69 97.2 90.2 99.7 2.363 1.822 3.066 PRE 40 23 57.5 40.9 73.0 8 20.0 9.1 35.6 0.079 0.051 0.121 PIII(M5) 71 71 100.0 94.9 100.0 71 100.0 94.9 100.0 2.823 2.376 3.354 MenC PRE 52 23 44.2 30.5 58.7 10 19.2 9.6 32.5 0.059 0.043 0.080 PIII(M5) 62 3 4.8 1.0 13.5 1 1.6 0.0 8.7 0.028 0.024 0.033 Hib PRE 48 18 37.5 24.0 52.6 8 16.7 7.5 30.2 0.055 0.039 0.077 PIII(M5) 67 66 98.5 92.0 100.0 66 98.5 92.0 100.0 2.651 2.079 3.380 PRE 31 29 93.5 78.6 99.2 20 64.5 45.4 80.8 0.367 0.203 0.664 PIII(M5) 65 65 100.0 94.5 100.0 64 98.5 91.7 100.0 4.095 3.037 5.520 PRE 33 25 75.8 57.7 88.9 18 54.5 36.4 71.9 0.227 0.121 0.427 PIII(M5) 65 65 100.0 94.5 100.0 65 100.0 94.5 100.0 5.592 4.238 7.378 PRE 31 26 83.9 66.3 94.5 16 51.6 33.1 69.8 0.258 0.143 0.467 PIII(M5) 68 68 100.0 94.7 100.0 68 100.0 94.7 100.0 4.309 3.306 5.616 MenC PRE 41 37 90.2 76.9 97.3 28 68.3 51.9 81.9 0.394 0.253 0.612 PIII(M5) 49 24 49.0 34.4 63.7 7 14.3 5.9 27.2 0.062 0.043 0.090 Hib PRE 43 39 90.7 77.9 97.4 30 69.8 53.9 82.8 0.388 0.247 0.609 PIII(M5) 65 65 100.0 94.5 100.0 64 98.5 91.7 100.0 4.372 3.211 5.954 PRE 40 20 50.0 33.8 66.2 10 25.0 12.7 41.2 0.073 0.049 0.109 PIII(M5) 67 66 98.5 92.0 100.0 66 98.5 92.0 100.0 3.518 2.748 4.504 PRE 40 19 47.5 31.5 63.9 6 15.0 5.7 29.8 0.063 0.045 0.090 PIII(M5) 71 71 100.0 94.9 100.0 70 98.6 92.4 100.0 2.969 2.464 3.578 PRE 37 21 56.8 39.5 72.9 8 21.6 9.8 38.2 0.075 0.050 0.111 PIII(M5) 72 72 100.0 95.0 100.0 72 100.0 95.0 100.0 2.936 2.440 3.533 MenC PRE 47 23 48.9 34.1 63.9 6 12.8 4.8 25.7 0.063 0.045 0.090 PIII(M5) 65 5 7.7 2.5 17.0 2 3.1 0.4 10.7 0.029 0.025 0.035 Hib PRE 47 25 53.2 38.1 67.9 10 21.3 10.7 35.7 0.078 0.054 0.112 PIII(M5) 67 66 98.5 92.0 100.0 65 97.0 89.6 99.6 3.326 2.557 4.327 PRE 42 28 66.7 50.5 80.4 14 33.3 19.6 49.5 0.124 0.076 0.202 PIII(M5) 65 65 100.0 94.5 100.0 65 100.0 94.5 100.0 2.303 1.889 2.806 PRE 42 28 66.7 50.5 80.4 18 42.9 27.7 59.0 0.126 0.083 0.190 PIII(M5) 67 66 98.5 92.0 100.0 66 98.5 92.0 100.0 1.846 1.444 2.360 PRE 36 25 69.4 51.9 83.7 16 44.4 27.9 61.9 0.129 0.080 0.206 PIII(M5) 66 66 100.0 94.6 100.0 66 100.0 94.6 100.0 2.061 1.719 2.472
MenC PRE 50 37 74.0 59.7 85.4 22 44.0 30.0 58.7 0.135 0.092 0.198 PIII(M5) 56 7 12.5 5.2 24.1 2 3.6 0.4 12.3 0.030 0.026 0.035 Hib PRE 45 28 62.2 46.5 76.2 15 33.3 20.0 49.0 0.115 0.073 0.180 PIII(M5) 65 65 100.0 94.5 100.0 63 96.9 89.3 99.6 1.881 1.508 2.346 Anti-23F PRE 41 17 41.5 26.3 57.9 5 12.2 4.1 26.2 0.053 0.038 0.075 PIII(M5) 66 65 98.5 91.8 100.0 64 97.0 89.5 99.6 2.581 1.970 3.381 PRE 43 14 32.6 19.1 48.5 6 14.0 5.3 27.9 0.045 0.033 0.062 PIII(M5) 68 66 97.1 89.8 99.6 64 94.1 85.6 98.4 2.112 1.544 2.891 PRE 38 15 39.5 24.0 56.6 7 18.4 7.7 34.3 0.062 0.040 0.096 PIII(M5) 70 67 95.7 88.0 99.1 67 95.7 88.0 99.1 2.098 1.551 2.838 MenC PRE 48 19 39.6 25.8 54.7 9 18.8 8.9 32.6 0.060 0.041 0.086 PIII(M5) 59 3 5.1 1.1 14.1 0 0.0 0.0 6.1 0.027 0.025 0.029 Hib PRE 48 22 45.8 31.4 60.8 8 16.7 7.5 30.2 0.065 0.044 0.098 PIII(M5) 66 63 95.5 87.3 99.1 62 93.9 85.2 98.3 1.988 1.426 2.772 Secondary Outcome Variable(s): Percentage of subjects reporting each solicited local symptom during the 8-day (Day 0-7) follow-up period by dose and across doses (Total Vaccinated cohort) MenC Hib Symptom Intensity N n % N n % N n % N n % N n % Dose 1 Pain Any 81 37 45.7 82 34 41.5 78 39 50.0 81 52 64.2 81 43 53.1 Grade 3 81 4 4.9 82 3 3.7 78 2 2.6 81 10 12.3 81 7 8.6 Redness Any 81 39 48.1 82 45 54.9 78 45 57.7 81 58 71.6 81 39 48.1 > 30 mm 81 1 1.2 82 1 1.2 78 2 2.6 81 6 7.4 81 2 2.5 Swelling Any 81 28 34.6 82 27 32.9 78 33 42.3 81 35 43.2 81 29 35.8 > 30 mm 81 2 2.5 82 0 0.0 78 0 0.0 81 4 4.9 81 3 3.7 Dose 2 Pain Any 81 33 40.7 82 33 40.2 76 31 40.8 81 34 42.0 81 37 45.7 Grade 3 81 3 3.7 82 1 1.2 76 1 1.3 81 3 3.7 81 5 6.2 Redness Any 81 50 61.7 82 53 64.6 76 43 56.6 81 56 69.1 81 56 69.1 > 30 mm 81 0 0.0 82 0 0.0 76 2 2.6 81 3 3.7 81 1 1.2 Swelling Any 81 37 45.7 82 40 48.8 76 35 46.1 81 41 50.6 81 43 53.1 > 30 mm 81 1 1.2 82 0 0.0 76 2 2.6 81 2 2.5 81 1 1.2 Dose 3 Pain Any 80 32 40.0 80 19 23.8 77 32 41.6 80 35 43.8 77 35 45.5 Grade 3 80 2 2.5 80 0 0.0 77 3 3.9 80 0 0.0 77 1 1.3 Redness Any 80 56 70.0 80 57 71.3 77 49 63.6 80 54 67.5 77 54 70.1 > 30 mm 80 3 3.8 80 1 1.3 77 2 2.6 80 2 2.5 77 1 1.3 Swelling Any 80 40 50.0 80 46 57.5 77 41 53.2 80 43 53.8 77 41 53.2 > 30 mm 80 1 1.3 80 0 0.0 77 0 0.0 80 0 0.0 77 0 0.0 Across doses Pain Any 81 54 66.7 82 50 61.0 79 53 67.1 81 66 81.5 82 60 73.2 Grade 3 81 8 9.9 82 4 4.9 79 5 6.3 81 13 16.0 82 10 12.2 Redness Any 81 67 82.7 82 67 81.7 79 64 81.0 81 75 92.6 82 69 84.1 > 30 mm 81 4 4.9 82 2 2.4 79 5 6.3 81 11 13.6 82 4 4.9 Swelling Any 81 53 65.4 82 64 78.0 79 56 70.9 81 60 74.1 82 58 70.7 > 30 mm 81 2 2.5 82 0 0.0 79 2 2.5 81 6 7.4 82 4 4.9
N = number of subjects with at least one symptom n/%= number/percentage of subjects reporting the symptom at least once Any = incidence of a particular local symptom regardless of intensity grade Grade 3 pain = cried when limb was moved/spontaneously painful Secondary Outcome Variable(s): Percentage of subjects reporting each solicited general symptom during the 8-day (Day 0-7) follow-up period by dose and across doses (Total Vaccinated cohort) MenC Hib Symptom Intensity/ Relationship N n % N n % N n % N n % N n % Dose 1 Drowsiness Any 80 58 72.5 82 57 69.5 78 47 60.3 81 55 67.9 81 56 69.1 Grade 3 80 1 1.3 82 0 0.0 78 2 2.6 81 0 0.0 81 4 4.9 Related 80 58 72.5 82 57 69.5 78 46 59.0 81 55 67.9 81 56 69.1 Irritability Any 80 61 76.3 82 63 76.8 78 64 82.1 81 73 90.1 81 68 84.0 Grade 3 80 6 7.5 82 4 4.9 78 10 12.8 81 5 6.2 81 5 6.2 Related 80 61 76.3 82 63 76.8 78 63 80.8 81 73 90.1 81 68 84.0 Loss of appetite Any 80 36 45.0 82 37 45.1 78 27 34.6 81 28 34.6 81 39 48.1 Grade 3 80 1 1.3 82 0 0.0 78 1 1.3 81 1 1.2 81 1 1.2 Related 80 36 45.0 82 35 42.7 78 27 34.6 81 28 34.6 81 39 48.1 Fever (rectal) 38 C 80 43 53.8 82 49 59.8 78 46 59.0 81 53 65.4 81 56 69.1 > 40 C 80 0 0.0 82 0 0.0 78 0 0.0 81 0 0.0 81 0 0.0 Related 80 43 53.8 82 46 56.1 78 46 59.0 81 53 65.4 81 55 67.9 Dose 2 Drowsiness Any 81 37 45.7 82 51 62.2 76 35 46.1 80 45 56.3 81 41 50.6 Grade 3 81 0 0.0 82 1 1.2 76 0 0.0 80 2 2.5 81 2 2.5 Related 81 37 45.7 82 51 62.2 76 35 46.1 80 45 56.3 81 40 49.4 Irritability Any 81 60 74.1 82 70 85.4 76 61 80.3 80 73 91.3 81 66 81.5 Grade 3 81 10 12.3 82 6 7.3 76 3 3.9 80 10 12.5 81 9 11.1 Related 81 58 71.6 82 70 85.4 76 60 78.9 80 72 90.0 81 66 81.5 Loss of appetite Any 81 24 29.6 82 26 31.7 76 27 35.5 80 20 25.0 81 28 34.6 Grade 3 81 1 1.2 82 0 0.0 76 0 0.0 80 0 0.0 81 0 0.0 Related 81 24 29.6 82 26 31.7 76 25 32.9 80 20 25.0 81 28 34.6 Fever (rectal) 38 C 81 46 56.8 82 40 48.8 76 40 52.6 80 38 47.5 81 44 54.3 > 40 C 81 0 0.0 82 1 1.2 76 0 0.0 80 0 0.0 81 0 0.0 Related 81 46 56.8 82 39 47.6 76 40 52.6 80 36 45.0 81 43 53.1 Dose 3 Drowsiness Any 80 24 30.0 80 32 40.0 77 32 41.6 80 36 45.0 77 34 44.2 Grade 3 80 0 0.0 80 0 0.0 77 0 0.0 80 0 0.0 77 2 2.6 Related 80 24 30.0 80 31 38.8 77 31 40.3 80 35 43.8 77 33 42.9 Irritability Any 80 55 68.8 80 52 65.0 77 53 68.8 80 55 68.8 77 62 80.5 Grade 3 80 6 7.5 80 5 6.3 77 5 6.5 80 4 5.0 77 4 5.2 Related 80 54 67.5 80 52 65.0 77 52 67.5 80 54 67.5 77 62 80.5 Loss of appetite Any 80 32 40.0 80 33 41.3 77 28 36.4 80 25 31.3 77 21 27.3 Grade 3 80 1 1.3 80 0 0.0 77 1 1.3 80 0 0.0 77 0 0.0 Related 80 30 37.5 80 31 38.8 77 27 35.1 80 25 31.3 77 21 27.3 Fever (rectal) 38 C 80 38 47.5 80 34 42.5 77 35 45.5 80 36 45.0 77 46 59.7 > 40 C 80 0 0.0 80 0 0.0 77 1 1.3 80 0 0.0 77 0 0.0 Related 80 35 43.8 80 33 41.3 77 34 44.2 80 35 43.8 77 45 58.4 Across doses Drowsiness All 81 65 80.2 82 72 87.8 78 58 74.4 81 70 86.4 82 67 81.7 Grade 3 81 1 1.2 82 1 1.2 78 2 2.6 81 2 2.5 82 6 7.3 Related 81 65 80.2 82 72 87.8 78 58 74.4 81 69 85.2 82 66 80.5 Irritability All 81 76 93.8 82 79 96.3 78 76 97.4 81 80 98.8 82 80 97.6
Loss of appetite Grade 3 81 19 23.5 82 14 17.1 78 18 23.1 81 17 21.0 82 16 19.5 Related 81 75 92.6 82 79 96.3 78 76 97.4 81 80 98.8 82 80 97.6 All 81 57 70.4 82 56 68.3 78 49 62.8 81 47 58.0 82 58 70.7 Grade 3 81 3 3.7 82 0 0.0 78 2 2.6 81 1 1.2 82 1 1.2 Related 81 55 67.9 82 56 68.3 78 48 61.5 81 47 58.0 82 58 70.7 Fever (rectal) 38 C 81 65 80.2 82 64 78.0 78 64 82.1 81 64 79.0 82 70 85.4 > 40 C 81 0 0.0 82 1 1.2 78 1 1.3 81 0 0.0 82 0 0.0 Related 81 63 77.8 82 64 78.0 78 63 80.8 81 63 77.8 82 70 85.4 N = number of subjects with at least one symptom n/%= number/percentage of subjects reporting the symptom at least once Any = incidence of a particular general symptom regardless of intensity or relationship to vaccinations Grade 3 = general symptom that prevented normal everyday activities Grade 3 Irritability = crying that could not be comforted/prevented normal activity Grade 3 Loss of appetite = not eating at all Related = general symptom assessed by the investigator as causally related to study vaccination Safety results: Number (%) of subjects with unsolicited adverse events within 31 days after vaccination (Total Vaccinated cohort) Most frequent adverse events - On-Therapy (occurring within day 0-30 following vaccination) N = 80 MenC N = 81 Hib Subjects with any AE(s), n (%) 64 (78.0) 68 (82.9) 56 (70.0) 58 (71.6) 68 (82.9) Upper respiratory tract infection 19 (23.2) 24 (29.3) 24 (30.0) 25 (30.9) 31 (37.8) Injection site bruising 12 (14.6) 12 (14.6) 15 (18.8) 16 (19.8) 11 (13.4) Irritability 13 (15.9) - 9 (11.3) 5 (6.2) 12 (14.6) Rhinorrhoea - 9 (11.0) - 10 (12.3) - Vomiting - 9 (11.0) 7 (8.8) - 9 (11.0) Diarrhoea - 10 (12.2) - 7 (8.6) Pyrexia 7 (8.5) - - - 8 (9.8) Teething 7 (8.5) - - - - Cough - - - 5 (6.2) - Rash 8 (9.8) - 7 (8.8) - - Gingival pain - - - 5 (6.2) - - Adverse event absent or not meeting the selected rule: More than 30 subjects per treatment group and > 3 groups: only the 5 most frequent events in each treatment group are listed Safety results: Number (%) of subjects with serious adverse events over the full course of the study (i.e. up to the post dose 3 visit): (Total Vaccinated cohort) Serious Adverse Events, n (%) [n considered by the investigator to be related to study medication] All SAEs N = 80 MenC N = 81 Hib Subjects with any SAE(s), n (%) [n assessed as 5 (6.1) [0] 5 (6.1) [0] 2 (2.5) [0] 4 (4.9) [0] 6 (7.3) [0] related by the investigator] Balanitis 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (1.2) [0] Bronchiolitis 1 (1.2) [0] 1 (1.2) [0] 1 (1.3) [0] 0 (0.0) [0] 4 (4.9) [0] Convulsion 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] Croup infectious 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Deafness 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] Escherichia urinary tract infection 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (1.2) [0] Gastroenteritis 1 (1.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Gastroenteritis viral 2 (2.4) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] Haematemesis 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Influenza 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Lobar pneumonia 1 (1.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Milk allergy 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Pneumonia 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0]
Sudden infant death syndrome 0 (0.0) [0] 0 (0.0) [0] 1 (1.3) [0] 0 (0.0) [0] 0 (0.0) [0] Tachycardia 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (1.2) [0] 0 (0.0) [0] Fatal SAEs D1 D2 D3 MenC Hib N = 80 N = 81 Subjects with fatal SAE(s), n (%)[n assessed as 0 (0.0) [0] 0 (0.0) [0] 1 (1.3) [0] 0 (0.0) [0] 0 (0.0) [0] related by the investigator] Sudden infant death syndrome 0 (0.0) [0] 0 (0.0) [0] 1 (1.3) [0] 0 (0.0) [0] 0 (0.0) [0] Conclusion: At one month post dose 3, 97.3% of subjects in, 98.7% of subjects in, 92.9% of subjects in, 89.2% of subjects in MenC and 94.6% of subjects in Hib had Anti-PRP antibodies concentration 1 g/ml. At the same time, 98.5%, 100% and 98.6% of subjects in, and groups, respectively, 14.7% of subjects in MenC and 16.2% of subjects in Hib had rsba-meny antibody titres 1:8. All subjects in,, & MenC groups and 1.3% of subjects in Hib had rsba-menc antibodies titres 1:8. During 31 days post each vaccination, at least one unsolicited AEs was reported for 64 (78.0%) subjects in, 68 (82.9%) subjects in, 56 (70.0%) subjects in, 58 (71.6%) subjects in MenC and 68 (82.9%) subjects in Hib. In both of the and groups, 5 subjects reported at least one SAE over the full course of the study. During the same time, 2 subjects in, 4 in the MenC and 6 in Hib reported at least one SAE. One fatal SAE due to Sudden Infant Death Syndrome was reported in. All the reported SAEs were assessed as not related to study vaccination by the investigators. Publications: T Nolan et al. A novel Haemophilus influenzae type b meningococcal serogroups C and Y conjugate (-TT) vaccine induces persistent immune responses and immune memory. Abstract presented at Pediatric Academic Societies (PAS) Annual meeting. San Francisco, California, US, 29 April to 2 May 2006. Nolan T et al (2007) A novel combined Haemophilus influenzae type b-neisseria meningitidis serogroups C and Y-tetanustoxoid conjugate vaccine is immunogenic and induces immune memory when co-administered with DTPa-HBV-IPV and conjugate pneumococcal vaccines in infants. Vaccine. 25 (51): 8487 8499. Bryant KA et al. (2011) Haemophilus influenzae type b Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers. Expert Rev Vaccines.10(7):941-950. Date updated: 16-May-2012