Study No.: Title: Rationale: Phase: Study Periods: Study Design: Centers: Indication: Treatment: Objectives:

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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.: Hib-MenC-TT-014 (106388) & Hib-MenC-TT-015 (106390) Title: A phase III, open, randomized, controlled, multicentre, primary and booster vaccination study to demonstrate the noninferiority of the meningococcal serogroup C and the Haemophilus influenzae type b immune response of GlaxoSmithKline (GSK) Biologicals Hib-MenC vaccine co-administered with Infanrix penta versus NeisVac-C co-administered with Infanrix hexa when given as two primary doses at 3 and 5 months of age as well as the immunogenicity of the Hib-MenC vaccine when given as a booster at 11 months of age and the persistence of antibodies prior to the administration of the booster dose. Menitorix (Hib-MenC): GlaxoSmithKline (GSK) Biologicals Haemophilus influenzae type b (Hib) - meningococcal serogroupc (MenC) - tetanus toxoid conjugate vaccine. Infanrix penta (DTPa-HBV-IPV): GSK Biologicals combined diphtheria-tetanus-acellular pertussis (DTPa) - hepatitis B - inactivated polio vaccine. NeisVac-C (MenC): Baxter s meningococcal serogroup C tetanus toxoid conjugate vaccine. Infanrix hexa (DTPa-HBV-IPV/Hib): GSK Biologicals combined DTPa - hepatitis B - inactivated polio - Haemophilus influenzae type b vaccine. Note: This study was conducted in two parts: the primary vaccination phase (Hib-MenC-TT-014) and the booster vaccination phase (Hib-MenC-TT-015 BST: 014). Rationale: The aim of the primary study was to demonstrate the non-inferiority of the meningococcal serogroup C and Hib immune response induced by 2 doses of Hib-MenC vaccine co-administered with DTPa-HBV-IPV vaccine at 3 and 5 months of age compared to MenC vaccine co-administered with DTPa-HBV-IPV/Hib vaccine. The aim of the booster study was to evaluate the immunogenicity and safety of a booster dose of the Hib-MenC vaccine given concomitantly with DTPa- HBV-IPV vaccine compared to MenC vaccine co-administered with DTPa-HBV-IPV/Hib vaccine given at 11 months of age as well as the persistence of Hib and MenC antibodies prior to the administration of the booster doses. Phase: III Study Periods: Primary study: 04 April 2006 to 23 November 2006 Booster study: 20 December 2006 to 16 July 2007 Study Design: Open, randomized (1:1), controlled, multi-centre study with 2 parallel study groups. Centers: This study was conducted at 16 centers (12 in Finland and 4 in Italy). Indication: Two-dose primary immunization course in healthy infants in the first year of life with a booster dose at 11 months of age against Haemophilus influenzae type b and meningococcal serogroup C diseases. Treatment: The treatment groups were as follows: : subjects received DTPa-HBV-IPV vaccine co-administered with Hib-MenC vaccine. : subjects received DTPa-HBV-IPV/Hib vaccine co-administered with MenC vaccine. In the 2-dose primary phase, the vaccines were administered at 3 and 5 months of age. The booster dose was given at 11 months of age. All vaccines were administered by deep intramuscular injection, the DTPa-containing vaccines into the right upper thigh and the meningococcal vaccines into the left anterolateral thigh. Objectives: At one month after the second dose (Post vaccination II, at 6 months of age): To demonstrate the non-inferiority of the meningococcal serogroup C immune response induced by Hib-MenC vaccine given concomitantly with DTPa-HBV-IPV vaccine when administered as a 2-dose primary vaccination course (3-5 month schedule), compared to MenC vaccine co-administered with DTPa-HBV-IPV/Hib vaccine, in terms of percentage of subjects with functional anti-meningococcal serogroup C activity/antibody (rsba*-menc) titer 1:8. (Criterion for meeting this objective: One month after the second dose, the lower limit of the standardized asymptotic 95% confidence interval (CI) on the difference between the study vaccine group and (minus) the control group was greater than or equal to -5 %.) * rsba - serum bactericidal assay using baby rabbit complement To demonstrate the non-inferiority of the Hib immune response induced by Hib-MenC vaccine given concomitantly with DTPa-HBV-IPV vaccine when administered as a 2-dose primary vaccination course (3-5 month schedule), compared to MenC vaccine co-administered with DTPa-HBV-IPV/Hib vaccine, in terms of percentage of subjects with anti-polyribosylribitol phosphate (anti-prp) antibody concentration 0.15 μg/ml.

2 (Criterion for meeting this objective: One month after the second dose, the lower limit of the standardized asymptotic 95% CI on the difference between the study vaccine group and (minus) the control group was greater than or equal to -10 %.) Primary Outcome/Efficacy Variable: One month after the second dose (Post vaccination II, at 6 months of age), in all subjects rsba-menc titer 1:8 Anti-PRP antibody concentration 0.15 μg/ml Secondary Outcome/Efficacy Variable(s): Immunogenicity One month after the second dose (PII(M3), at 6 months of age), in all subjects rsba-menc titer 1:128 and titers. Anti-serogroup C polysaccharide (anti-psc) antibody concentration 0.30 μg/ml, 2 μg/ml and concentrations. Anti-PRP antibody concentration 1.0 μg/ml and concentrations. Anti-hepatitis B surface antigen (anti-hbs) antibody concentration 10 miu/ml and concentrations. Prior to (pre-booster, at 11 months of age) and one month after the booster vaccination (post-booster, at 12 months of age), in all subjects: rsba-menc titer 1:8, 1:128 and concentrations. Anti-PSC antibody concentration 0.30 μg/ml, 2 μg/ml and concentrations. Anti-PRP antibody concentration 0.15 μg/ml, 1 μg/ml and concentrations. Anti-HBs antibody concentration 10 miu/ml, 100 miu/ml, and concentration. Safety Occurrence of local solicited adverse events (AEs) during the solicited follow-up period (Day 0-3) following the administration of each vaccine dose. Occurrence of solicited general adverse events, during the solicited follow-up period (Day 0-3) following the administration of each vaccine dose. Occurrence of unsolicited non-serious adverse events within 30 days after each vaccination. Occurrence of any serious adverse events (SAEs) throughout the study. Statistical Methods: Primary study The analyses for the primary study phase were done on the Primary Total Vaccinated Cohort and the Primary According- To-Protocol (ATP) cohort for immunogenicity. -The Primary Total Vaccinated Cohort included all vaccinated subjects for whom data were available for the primary phase. Thus, for the Primary Total Vaccinated Cohort, the analysis of safety included all subjects with at least one vaccine administration documented. - The Primary ATP cohort for immunogenicity included all evaluable subjects who had received at least one dose of study vaccine/comparator according to their random assignment, for whom administration site of study vaccine/comparator was known, who had not received a vaccine not specified or forbidden in the protocol, who met all eligibility criteria, who complied with the procedures defined in the protocol and for whom data concerning immunogenicity measures were available with respect to primary vaccination. Analysis of immunogenicity The analysis was done on the Primary ATP cohort for immunogenicity. Inferential analysis: One month after the second dose, the standardized asymptotic 95% CI was computed for the difference between the minus the in terms of rsba-menc seroprotected subjects (rsba-menc titer 1:8). The same calculations were done for anti-prp seroprotected subjects (Anti-PRP antibody concentration 0.15 μg/ml). The noninferiority objective was met if the lower limit of the 95% CIs was above 5% for rsba-menc and -10% for anti-prp. Descriptive analysis For each treatment group, one month after the second dose of the primary vaccination course, for each antibody for which results were available, geometric mean concentrations or geometric mean titers (GMCs or GMTs) with 95% CIs were calculated. Also seropositivity / seroprotection rates with exact 95% CIs were tabulated. For GMC or GMT calculations, antibody concentrations or titers below the assay cut-off were given an arbitrary value of half the cut-off. Analysis of safety The analysis of safety was performed on the Primary Total Vaccinated Cohort. For each solicited local or general symptom, the percentage of subjects with the symptom reported during the 4-day (Day 0-3) follow-up period after each vaccination was summarized with exact 95% CI for each group. The same calculations were done for Grade 3 local or general symptoms and for general symptoms that were related to the vaccination. The percentage of subjects with unsolicited AEs within 31 days (Day 0-30) following vaccine dose was tabulated according

3 to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. The occurrence of SAEs during the entire study period was tabulated according to the MedDRA preferred terms. Booster study The analyses were performed on the Booster Total Vaccinated Cohort, Booster ATP cohort for antibody persistence and Booster ATP cohort for immunogenicity. -The Booster Total Vaccinated Cohort included all subjects with booster vaccine administration documented. -The Booster ATP cohort for antibody persistence included all subjects who had received all vaccine doses in the primary vaccination course, who had received the booster vaccine doses, and who had not received a vaccine not specified or forbidden in the protocol. -The Booster ATP cohort for immunogenicity included all subjects who had received all vaccine doses in the primary vaccination course, who had received the booster vaccine doses, who had not received a vaccine not specified or forbidden in the protocol, and who met all eligibility criteria as defined in the report and analysis plan. Analysis of persistence The analysis was performed on the Booster ATP cohort for antibody persistence. For both groups, and for each antibody, post-primary vaccination course and just before the administration of the booster dose, percentages of subjects above the specified cut-offs with exact 95% CIs and GMCs or GMTs with 95% CIs were calculated. For GMC or GMT calculations, antibody concentrations or titers below the assay cut-off were given an arbitrary value of half the cut-off. Analysis of immunogenicity The analysis was performed on the Booster ATP cohort for immunogenicity. For both groups, before and 31 days after the booster dose for the evaluation of the immune response, for each antibody for which results were available, percentages of subjects above the specified cut-offs with exact 95% CIs and GMCs or GMTs with 95% CIs were calculated. Inferential Analysis (pre-specified as part of the secondary objectives). The evaluation of the co-secondary non-inferiority objectives was performed as follows: Prior to the administration of the booster dose (Pre-boost), the standardized asymptotic 95% CI was computed for the difference between the minus in terms of percentage of subjects with rsba-menc titre 1:8. The non-inferiority objective was met if the lower limit of the 95% CIs was above 10% (clinical limit of non-inferiority). Prior to the administration of the booster dose (Pre-boost), the standardized asymptotic 95% CI was computed for the difference between the minus in terms of percentage of subjects with anti-prp antibody concentrations 0.15μg/ml. The non-inferiority objective was met if the lower limit of the 95% CIs was above -10% (clinical limit of non-inferiority). Analysis of safety The analysis was performed on the Booster Total Vaccinated Cohort. For each group, the percentages of subjects with each individual solicited local (any and grade 3) and general (any, grade 3 and related) symptoms reported during the 4-day (Day 0-3) solicited follow-up period after booster vaccination were tabulated with exact 95% CI. The percentages of subjects with unsolicited AEs reported up to 30 days after booster vaccination were tabulated per group, according to the MedDRA preferred terms. The occurrences of SAEs between 31 days after the primary vaccination course and the start of the Booster study were tabulated per group according to the MedDRA preferred terms on the Primary Total Vaccinated Cohort. The occurrences of SAEs from the start of the Booster vaccination until the end of the Booster study were tabulated per group according to the MedDRA preferred terms on the Booster Total Vaccinated Cohort. Study Population: Healthy male or female infants, between and including 6 and 12 weeks of age at the time of first vaccination, free of obvious health problems and born after a gestation period of weeks were included in this study. Written informed consent was obtained from parent(s)/guardian(s) of the subject prior to study entry. Subjects with previous booster vaccination for Hib, a serogroup C meningococcal or a DTPa, IPV or Hep B containing vaccine were not enrolled in the booster study. Number of subjects in the primary study Planned, N Randomized, N (Primary Total Vaccinated Cohort) Completed, n (%) 346 (97.5) 349 (98.6) Total Number Subjects Withdrawn, n (%) 9 (2.5) 5 (1.4) Withdrawn due to Adverse Events, n (%) 8 (2.3) 2 (0.6) Withdrawn due to Lack of Efficacy, n (%) Not applicable Not applicable Withdrawn for other reasons, n (%) 1 (0.3) 3 (0.8) Demographics N (Primary Total Vaccinated Cohort)

4 Females: Males 170: :196 Mean Age, weeks (SD) 10.8 (1.19) 10.8 (1.21) White - Caucasian, n (%) 350 (98.6) 351 (99.2) Primary Study Primary Efficacy Results: Difference between groups in terms of percentages of subjects with rsba-menc titer 1:8 and anti-prp antibody concentration 0.15 μg/ml one month after the second dose (Primary ATP cohort for immunogenicity) Antibody Criteria Group 1 N % Group 2 N % Difference in seroprotection rates (Group 1 minus Group 2) Difference % 95% CI LL UL rsba-menc 1:8 HibMenC MenC HibMenC MenC * 0.29 Anti-PRP 0.15μg/mL HibMenC MenC HibMenC MenC ** 4.62 % = percentage of subjects with specified antibody titer or concentration 95% CI = 95% standardized asymptotic confidence interval; LL = lower limit, UL = upper limit *The first co-primary objective for non-inferiority was met since the LL of the 95% CI was above the pre-specified -5%. **The second co-primary objective for non-inferiority was met since the LL of the 95% CI was above the pre-specified -10%. Primary Efficacy Results: Percentage of subjects with antibody titer > 1:8 or 1:128 and GMTs for rsba-menc antibodies (Primary ATP cohort for immunogenicity) Group Timing N 1:8* 1:128 GMT n % 95% CI n % 95% CI Value 95% CI LL UL LL UL LL UL HibMenC PII(M3) MenC PII(M3) n (%) = number (percentage) of subjects with antibody titer within the specified range PII(M3) = post-dose 2 blood sample at Month 3 *Primary Efficacy results Primary Efficacy Results: Seroprotection rates and GMCs for anti-prp antibodies (Primary 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 HibMenC PII(M3) MenC PII(M3) PII(M3) = post-dose 2 blood sample at Month 3 *Primary Efficacy results Seropositivity rates and GMCs for anti-psc antibodies (Primary ATP cohort for immunogenicity) Group Timing N 0.3 μg/ml 2 μg/ml GMC (μg/ml) n % 95% CI n % 95% CI Value 95% CI LL UL LL UL LL UL HibMenC PII(M3) MenC PII(M3) PII(M3) = post-dose 2 blood sample at Month 3

5 Seroprotection rates and GMCs for anti-hbs antibodies (Primary ATP cohort for immunogenicity) Group Timing N 10 miu/ml GMC (miu/ml) n % 95% CI Value 95% CI LL UL LL UL HibMenC PII(M3) MenC PII(M3) PII(M3) = post-dose 2 blood sample at Month 3 Number (percentage) of subjects with solicited local symptoms during the 4-day (Day 0-3) post-vaccination period following each dose and overall (Primary Total vaccinated Cohort) Symptom Intensity N n % 95% CI N n % 95% CI LL UL LL UL 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 Across Doses Pain Any Grade Redness Any > 30 mm Swelling Any > 30 mm N = number of subjects with an administered dose n (%) = number (percentage) of subjects with at least one local symptom whatever the number of injections. 95% CI = exact 95% confidence interval; LL = lower limit, UL = upper limit Any = incidence of a particular symptom regardless of intensity Grade 3 Pain = cried when limb was moved/spontaneously painful Number (percentage) of subjects with solicited general symptoms during the 4-day (Day 0-3) post-vaccination period following each dose and overall (Primary Total vaccinated Cohort) Symptom Intensity/ relationship N n % 95% CI N n % 95% CI LL UL LL UL Dose 1 Drowsiness Any Grade Related Fever (rectally) 38.0 C > 40.0 C

6 Related Irritability Any Grade Related Loss of appetite Any Grade Related Dose 2 Drowsiness Any Grade Related Fever (rectally) 38.0 C > 40.0 C Related Irritability Any Grade Related Loss of appetite Any Grade Related Across Doses Drowsiness Any Grade Related Fever (rectally) 38.0 C > 40.0 C Related Irritability Any Grade Related Loss of appetite Any Grade Related N = number of subjects with an administered 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 = incidence of a particular symptom regardless of intensity and relationship to 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 = not eating at all Related = symptoms considered by the investigator to have a causal relationship to study vaccination Safety Results: Number (%) of subjects with unsolicited adverse events during the primary vaccination (Primary Total Vaccinated Cohort) Most frequent adverse events - On-Therapy (occurring within Day 0-30 following primary vaccination) N = 355 N = 354 Subjects with any AE(s), n (%) 149 (42.0) 149 (42.1) Injection site induration 33 (9.3) 26 (7.3) Rhinitis 21 (5.9) 15 (4.2) Pyrexia 13 (3.7) 12 (3.4) Upper respiratory tract infection 7 (2.0) 16 (4.5) Vomiting 9 (2.5) 12 (3.4) Diarrhea 12 (3.4) 8 (2.3) Teething 11 (3.1) 7 (2.0) Otitis media 8 (2.3) 9 (2.5)

7 Conjunctivitis 9 (2.5) 6 (1.7) Rash 9 (2.5) 6 (1.7) Cough 5 (1.4) 7 (2.0) Injection site bruising 4 (1.1) 8 (2.3) Safety Results: Number (%) of subjects with Serious Adverse Events (SAEs) during the primary study (Primary Total Vaccinated Cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs N = 355* N = 354* Subjects with any SAE(s), n (%) [n related] 10 (2.8) [0] 4 (1.1) [0] Aorticopulmonary septal defect 1 (0.3) [0] 0 (0.0) [0] Bronchiolitis 1 (0.3) [0] 0 (0.0) [0] Concussion 1 (0.3) [0] 0 (0.0) [0] Epididymitis 1 (0.3) [0] 0 (0.0) [0] Gastroenteritis 0 (0.0) [0] 1 (0.3) [0] Interruption of aortic arch 1 (0.3) [0] 0 (0.0) [0] Laurence-moon-bardet-biedl syndrome 1 (0.3) [0] 0 (0.0) [0] Neurological examination 1 (0.3) [0] 0 (0.0) [0] Oral candidiasis 0 (0.0) [0] 1 (0.3) [0] Petit mal epilepsy 1 (0.3) [0] 0 (0.0) [0] Pneumococcal sepsis 0 (0.0) [0] 1 (0.3) [0] Pyelonephritis 0 (0.0) [0] 1 (0.3) [0] Pyelonephritis acute 1 (0.3) [0] 0 (0.0) [0] Skull fracture 1 (0.3) [0] 0 (0.0) [0] Sleep apnea syndrome 1 (0.3) [0] 0 (0.0) [0] Tremor neonatal 1 (0.3) [0] 0 (0.0) [0] Urinary tract infection 1 (0.3) [0] 0 (0.0) [0] Fatal SAEs Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] *8 subjects had their last study visit/last study contact days after the last vaccination of the primary phase. Booster Study The Booster Total Vaccinated Cohort counted 690 subjects: 340 subjects in the and 350 in the MenC Group; 338 and 345 subjects from the and the, respectively, completed the booster study. Difference between HibMenC and MenC groups in terms of percentage of subjects with rsba-menc titer 1:8 and anti-prp antibody concentration 0.15 μg/ml before booster vaccination (Booster ATP cohort for antibody persistence) Antibody Criteria Group N % Group N % Difference in seropositivity rates 95 % CI Between groups % LL UL rsba- MenC 1:8 HibMenC MenC HibMenC MenC -5.52* Anti-PRP 0.15μg/mL HibMenC MenC HibMenC MenC -1.28* % = percentage of subjects with concentration or titers the specified cut-off 95% CI = 95% Standardized asymptotic confidence interval; LL = lower limit, UL = upper limit *Non-inferiority objective was met since the LL were > -10 Percentage of subjects with rsba-menc antibody titer 1:8 or 1:128 and GMTs (Booster ATP cohort for antibody persistence) Group Timing N 1:8 1:128 GMT n % LL UL n % LL UL Value LL UL HibMenC PII(M3) Pre

8 MenC PII(M3) Pre n (%) = number (percentage) of subjects with titer within the specified range PII(M3) = Post-dose 2 blood sample at Month 3 Pre = Pre-booster blood sample at Month 9 Seropositivity rates and percentage of subjects with anti-psc antibody concentrations 0.3µg/mL or 2µg/mL and GMCs (Booster ATP cohort for antibody persistence) Group Timing N 0.3µg/mL 2µg/mL GMC (µg/ml) n % LL UL N % LL UL value LL UL HibMenC PII(M3) Pre MenC PII(M3) Pre PII(M3) = Post-dose 2 blood sample at Month 3 Pre = Pre-booster blood sample at Month 9 Seropositivity rates and percentage of subjects with anti-prp antibody concentrations 0.15µg/mL or 1µg/mL and GMCs (Booster ATP cohort for antibody persistence) Group Timing N 0.15µg/mL 1µg/mL GMC(µg/mL) n % LL UL N % LL UL value LL UL HibMenC PII(M3) Pre MenC PII(M3) Pre PII(M3) = Post-dose 2 blood sample at Month 3 Pre = Pre-booster blood sample at Month 9 Seropositivity rates and percentage of subjects with anti-hbs antibody concentrations 10 miu/ml and GMCs (Booster ATP cohort for antibody persistence) Group Timing N 10 miu/ml GMC (miu/ml) 95% CI 95% CI n % LL UL value LL UL HibMenC PII(M3) Pre MenC PII(M3) Pre PII(M3) = Post-dose 2 blood sample at Month 3 Pre= Pre-booster blood sample at Month 9 Percentage of subjects with rsba-menc antibody titer 1:8 or 1:128 and GMTs pre and post booster vaccination (Booster ATP cohort for immunogenicity)

9 Group Timing N 1:8 1:128 GMT n % LL UL n % LL UL value LL UL HibMenC Pre Post MenC Pre Post n (%) = number (percentage) of subjects with titer within the specified range Pre = Pre-booster blood sample at Month 9 Post = Post-booster blood sample at Month 10 Seropositivity rates and percentage of subjects with anti-psc antibodies 0.3µg/mL or 2µg/mL and GMCs, pre and post booster vaccination (Booster ATP cohort for immunogenicity) Group Timing N 0.3µg/mL 2µg/mL GMC(µg/mL) n % LL UL n % LL UL value LL UL HibMenC Pre Post MenC Pre Post Pre = Pre-booster blood sample at Month 9 Post = Post-booster blood sample at Month 10 Seropositivity rates and percentage of subjects with anti-prp antibodies 0.15µg/mL and 1µg/mL and GMCs, pre and post-booster vaccination (Booster ATP cohort for immunogenicity) Group Timing N 0.15µg/mL 1µg/mL GMC (µg/ml) n % LL UL N % LL UL value LL UL HibMenC Pre Post MenC Pre Post Pre = Pre-booster blood sample at Month 9 Post = Post-booster blood sample at Month 10 Seropositivity rates and percentage of subjects with anti-hbs antibodies 10 miu/ml or 100 miu/ml and GMCs, pre and post-booster vaccination (Booster ATP cohort for immunogenicity) Group Timing N 10 miu/ml 100 miu/ml GMC (miu/ml) n % LL UL n % LL UL value LL UL HibMenC Pre Post MenC Pre Post

10 Pre = Pre-booster blood sample at Month 9 Post = Post-booster blood sample at Month 10 Number (percentage) of subjects with solicited local symptoms reported during the 4-day (Day 0-3) post-booster vaccination period (Booster Total Vaccinated Cohort) Symptom Intensity 95 % CI 95 % CI N n % LL UL N n % LL UL Pain Any Grade Redness Any >30 mm Swelling Any >30 mm N= number of subjects with an administered 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 = incidence of a particular symptom regardless of intensity 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-booster vaccination period (Booster Total Vaccinated Cohort) Symptom Intensity/ Relationship 95 % CI 95 % CI N n % LL UL N n % LL UL Drowsiness Any Grade Related Irritability Any Grade Related Loss of appetite Fever (Rectally) Any Grade Related C > 40.0 C Related N = number of subjects with an administered 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 = incidence of a particular symptom regardless of intensity and relationship to 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 = not eating at all Related = symptoms considered by the investigator to have a causal relationship to study vaccination Safety Results: Number (%) of subjects with unsolicited adverse events during the booster study (Booster Total Vaccinated Cohort) Most frequent adverse events - On-Therapy (occurring within Day 0-30 following booster vaccination) N = 340 N = 350 Subjects with any AE(s), n (%) 143 (42.1) 141 (40.3) Otitis media 44 (12.9) 29 (8.3) Upper respiratory tract infection 17 (5.0) 33 (9.4) Injection site induration 18 (5.3) 20 (5.7) Pyrexia 18 (5.3) 19 (5.4) Gastroenteritis 14 (4.1) 12 (3.4)

11 Rhinitis 9 (2.6) 11 (3.1) Cough 8 (2.4) 9 (2.6) Respiratory tract infection 6 (1.8) 11 (3.1) Diarrhea 6 (1.8) 9 (2.6) Ear infection 6 (1.8) 7 (2.0) Safety Results: Number (%) of subjects with Serious Adverse Events since the end of the primary phase until the start of the booster vaccination (Primary Total Vaccinated Cohort) All SAEs N = 355* N = 354* Subjects with any SAE(s), n (%) [n related] 10 (2.8) [0] 10 (2.8) [0] Gastroenteritis 6 (1.7) [0] 2 (0.6) [0] Bronchitis chronic 0 (0.0) [0] 3 (0.8) [0] Arthritis reactive 1 (0.3) [0] 0 (0.0) [0] Bronchitis 1 (0.3) [0] 0 (0.0) [0] Fatigue 0 (0.0) [0] 1 (0.3) [0] Foreign body trauma 1 (0.3) [0] 0 (0.0) [0] Gastroenteritis rotavirus 0 (0.0) [0] 1 (0.3) [0] Poisoning 1 (0.3) [0] 0 (0.0) [0] Pyelonephritis 1 (0.3) [0] 0 (0.0) [0] Pyelonephritis acute 0 (0.0) [0] 1 (0.3) [0] Tibia fracture 0 (0.0) [0] 1 (0.3) [0] Viral tonsillitis 0 (0.0) [0] 1 (0.3) [0] Fatal SAEs HibMenC N = 355 MenC N = 354 Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] *8 subjects had their last study visit/last study contact days after the last vaccination of the primary phase Safety Results: Number (%) of subjects with Serious Adverse Events from the start of the booster vaccination until the end of the booster study (Booster Total Vaccinated Cohort) All SAEs N = 340 N = 350 Subjects with any SAE(s), n (%) [n related] 5 (1.5) [0] 8 (2.3) [0] Gastroenteritis 3 (0.9) [0] 1 (0.3) [0] Asthma 0 (0.0) [0] 2 (0.6) [0] Gastroenteritis rotavirus 1 (0.3) [0] 1 (0.3) [0] Pneumonia 1 (0.3) [0] 1 (0.3) [0] Bronchitis 1 (0.3) [0] 0 (0.0) [0] Bronchitis chronic 0 (0.0) [0] 1 (0.3) [0] Febrile convulsion 0 (0.0) [0] 1 (0.3) [0] Laryngitis 0 (0.0) [0] 1 (0.3) [0] Fatal SAEs HibMenC MenC N = 340 N = 350 Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] Conclusion: One month after the second vaccination, 99.1% and 100% of the subjects from the and the, respectively, had rsba-menc antibody titers 1:8. At the same time point, 96.9% and 95.5% of the subjects from the and the, respectively, had anti-prp antibody concentrations 0.15 μg/ml. Prior to the booster dose, at least 94.5% and 86.1% of subjects had rsba-menc antibody titers 1:8 and anti-prp antibody concentrations 0.15 μg/ml, respectively. One month after booster vaccination, all subjects had rsba-menc antibody titers 1:8 and anti-prp antibody concentrations 0.15 μg/ml. During the primary study phase, unsolicited AEs were reported for 149 (42.0%) subjects from the and 149 (42.1%) of the ; after booster vaccination, unsolicited AEs were reported for 143 (42.1%) subjects from the and 141 (40.3%) of the MenC Group. During the primary study phase, SAEs were reported for 10 (2.8%) and 4 (1.1%) of the subjects from the HibMenC Group and the, respectively; between the primary and the booster phase, SAEs were reported for 20 (2.8%) subjects, 10 in each group; after booster vaccination, SAEs were reported for 5 (1.5%) and 8 (2.3%) subjects from the and the, respectively. None of the SAEs reported during any study phase was considered by

12 the investigators to be related to the study vaccination. No fatal SAEs were reported during the whole course of the study. Date updated: 12-September-2014