Study No.: Title: Rationale: Note: Phase: Study Period: Study Design: Centres: Indication: Treatment: Hib-MenCY F1 Group Hib-MenCY F2 Group

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Roxanne Mosley
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1 The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: /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 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:

2 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.

3 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 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 Randomised, N (Total Vaccinated cohort) 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) 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 Hib minus Hib minus % = 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 MenC minus MenC minus % = 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 minus minus % = percentage of subjects with rsba-meny titre 1:8

4 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 Hib MenCY Hib MenCY MenC Hib 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) Secondary Outcome Variable(s): Percentage of subjects with rsba-menc titres 1:8 and GMTs (ATP cohort for Timing N 1:8 GMT PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) n/% = number/percentage of subjects with titre within the specified range GMT: Geometric mean antibody titre

5 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE

6 PIII(M5) Hib PRE PIII(M5) 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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)

7 Anti-PT PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) Anti-FHA PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) Anti-PRN PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5)

8 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 PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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 PIII(M5)

9 Anti-6B Anti-9V Anti-14 Anti-18C Anti-19F PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) PRE PIII(M5)

10 MenC PRE PIII(M5) Hib PRE PIII(M5) Anti-23F PRE PIII(M5) PRE PIII(M5) PRE PIII(M5) MenC PRE PIII(M5) Hib PRE PIII(M5) 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 Grade Redness Any > 30 mm Swelling Any > 30 mm Dose 2 Pain Any Grade Redness Any > 30 mm Swelling Any > 30 mm Dose 3 Pain Any Grade Redness Any > 30 mm Swelling Any > 30 mm Across doses Pain Any Grade Redness Any > 30 mm Swelling Any > 30 mm

11 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 Grade Related Irritability Any Grade Related Loss of appetite Any Grade Related Fever (rectal) 38 C > 40 C Related Dose 2 Drowsiness Any Grade Related Irritability Any Grade Related Loss of appetite Any Grade Related Fever (rectal) 38 C > 40 C Related Dose 3 Drowsiness Any Grade Related Irritability Any Grade Related Loss of appetite Any Grade Related Fever (rectal) 38 C > 40 C Related Across doses Drowsiness All Grade Related Irritability All

12 Loss of appetite Grade Related All Grade Related Fever (rectal) 38 C > 40 C Related 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) (9.8) Teething 7 (8.5) Cough (6.2) - Rash 8 (9.8) - 7 (8.8) - - Gingival pain (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]

13 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 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): 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): Date updated: 16-May-2012

To demonstrate that DTPa-HBV-IPV/Hib-MenC-TT co-administered with 10Pn, is non-inferior to DTPa-HBV-IPV/Hib coadministered

To demonstrate that DTPa-HBV-IPV/Hib-MenC-TT co-administered with 10Pn, is non-inferior to DTPa-HBV-IPV/Hib coadministered 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.