Analysis of safety The analysis was performed on the Total Vaccinated cohort.

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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.: (10PN-PD-DIT-066) Title: Primary vaccination course with the pneumococcal vaccine GSK A, in healthy infants in Vietnam when coadministered with GSK Biologicals Infanrix hexa (DTPa-HBV-IPV/Hib) vaccine. Synflorix GSK A (10Pn): GlaxoSmithKline (GSK) Biologicals 10-valent pneumococcal conjugate vaccine. Infanrix hexa (DTPa-HBV-IPV/Hib): GSK Biologicals combined diphtheria-tetanus-acellular pertussis-hepatitis B virusinactivated poliovirus and Haemophilus influenzae type b vaccine. Rationale: The aim of this study was to evaluate the safety of 10Pn vaccine given as a 3-dose primary immunization course when co-administered with DTPa-HBV-IPV/Hib vaccine at 2, 3 and 4 months of age in infants in Vietnam. Phase: III Study Period: 17 February 2011 to 26 July Study Design: open, randomised (2:1) study with 2 parallel groups. Centres: 1 centre in Vietnam Indication: Primary vaccination against Streptococcus pneumoniae in healthy infants between 6 to 12 weeks of age at the time of the first vaccination. Treatment: The study groups were as follows: : subjects received 10Pn vaccine co-administered along with DTPa-HBV-IPV/Hib vaccine. : subjects received DTPa-HBV-IPV/Hib vaccine alone. All vaccines were administered according to a 3-dose schedule at 2, 3 and 4 months of age. The 10Pn and DTPa-HBV- IPV/Hib vaccines were administered by intramuscular injection, 10Pn in the right thigh, DTPa-HBV-IPV/Hib in the left thigh. Objectives: To evaluate the safety of 10Pn vaccine when co-administered with DTPa-HBV-IPV/Hib vaccine as a 3-dose primary vaccination course at 2, 3 and 4 months of age, in terms of grade 3 solicited and unsolicited adverse events (AEs). Primary Outcome Variable: Occurrence of grade 3 AEs for solicited (Day 0 - Day 3) and unsolicited within 31 days (Day 0 - Day 30) after primary vaccination with 10Pn vaccine when co-administered with DTPa-HBV-IPV/Hib vaccine. Secondary Outcome Variables: Occurrence of each solicited AEs within 4 days after each vaccination. Local (any, grade 3) AEs. General (any, grade 3, related) AEs. Occurrence of unsolicited AEs within 31 days after each vaccination. Occurrence of serious adverse events (SAEs) after the first vaccination up to study end. Statistical Methods: The analysis was performed on the Total Vaccinated cohort. The Total Vaccinated cohort included all vaccinated subjects with at least one vaccine administration documented. Analysis of safety The analysis was performed on the Total Vaccinated cohort. The percentage of grade 3 AEs (solicited and unsolicited) during the 31-day (Days 0-30) after primary vaccination was tabulated in the. The percentage of subjects reporting each individual solicited local and general symptom during the 4-day (Days 0-3) postvaccination follow-up period was calculated with exact 95 % confidence interval (CI) for both groups after each dose and across doses. The same tabulation was performed for Grade 3 solicited symptoms and for solicited general symptoms assessed by the investigators as causally related to the vaccination. All local symptoms were considered as causally related to the vaccination. The proportion of subjects with at least one unsolicited AE within the 31-day (Day 0-30) post-vaccination follow-up period was tabulated according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. SAEs occurring during the entire study period were also tabulated according to MedDRA preferred terms. Study Population: Healthy male or female subjects between, and including 6-12 weeks (42-90 days) of age at the time of

2 the first vaccination. Subjects who received previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenza type b and/or Streptococcus pneumoniae were excluded from the study. Written informed consent was obtained from the parent(s)/legally acceptable representative(s) of the subjects prior to the study entry. Number of subjects Planned, N Randomized, N (Total Vaccinated cohort) Completed, n (%) 193 (97.0) 99 (100) Total Number Subjects Withdrawn, n (%) 6 (3.0) 0 (0.0) Withdrawn due to Adverse Events n (%) 1 (0.5) 0 (0.0) Withdrawn due to Lack of Efficacy n (%) Not applicable Not applicable Withdrawn for other reasons n (%) 5 (2.5) 0 (0.0) Demographics N (Total Vaccinated cohort) Females: Males 93:106 37:62 Mean Age, weeks (SD) 8.8 (1.24) 8.7 (1.11) Asian - South East Asian Heritage, n (%) 199 (100) 99 (100) Primary Efficacy Results: Incidence and nature of grade 3 symptoms (solicited and unsolicited) reported during the 31-day (Days 0-30) post-vaccination period following each dose and across doses (Total Vaccinated cohort) Any symptom* General symptoms Local symptoms 95% CI 95% CI 95% CI Group N n % LL UL N n % LL UL N n % LL UL 10Pn Hexa Pn Hexa Pn Hexa Pn Hexa N= number of subjects with at least one documented dose n/%= number/percentage of subjects presenting at least one type of symptom whatever the study vaccine administered 95% CI = exact 95% confidence interval, LL = Lower Limit, UL = Upper Limit Grade 3 symptom: symptom that prevented normal activity *Primary outcome variable Secondary Outcome Variable(s): Number (%) of subjects reporting solicited local symptoms reported during the 4-day (Days 0-3) post-vaccination period following each dose and across doses (Total Vaccinated cohort) Symptom Intensity N n % LL UL Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Pain Any

3 Grade Redness Any >30 mm Swelling Any >30 mm Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Symptom Intensity N n % LL UL Pain Any Grade Redness Any >30 mm Swelling Any Pain Any Grade Redness Any >30 mm Swelling Any >30 mm Pain Any Redness Any Swelling Any Pain Any Grade Redness Any Swelling Any >30 mm N= number of subjects with at least one documented dose n/%= number/percentage of subjects reporting at least once the symptom 95%95% CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = incidence of a particular symptom regardless of intensity grade

4 Grade 3 pain = cried when limb was moved / spontaneously painful Secondary Outcome Variable(s): Number (%) of subjects reporting solicited general symptoms reported during the 4-day (Days 0-3) post-vaccination period following each dose and across doses (Total Vaccinated cohort) Symptom Intensity/ relationship N n % LL UL Drowsiness Any Grade Related Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Grade Related Loss of appetite Any Grade Related Drowsiness Any Related Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Grade Related Loss of appetite Any Related Drowsiness Any Related Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Grade Related Loss of appetite Any Related Drowsiness Any Grade Related Fever (Axillary) 37.5 C >39.5 C

5 Related Irritability Any Grade Related Loss of appetite Any Grade Related Symptom Intensity/ relationship N n % LL UL Drowsiness Any Related Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Grade Related Loss of appetite Any Related Drowsiness Any Related Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Related Loss of appetite Any Related Drowsiness Any Related Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Related Loss of appetite Any Related Drowsiness Any Related

6 Fever (Axillary) 37.5 C >39.5 C Related Irritability Any Grade Related Loss of appetite Any Related N= number of subjects with at least one documented dose n/%= number/percentage of subjects reporting the symptom 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 or relationship to vaccination Grade 3 drowsiness = drowsiness which 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 = solicited symptom assessed by the investigator to have a causal relationship to study vaccination Safety Results: Number (%) of subjects with unsolicited adverse events reported during the 31-day (Days 0-30) follow-up period after each dose (Total Vaccinated cohort) Most frequent adverse events - On-Therapy (occurring within Days 0-30 following vaccination) N = 199 N = 99 Subjects with any AE(s), n (%) 57 (28.6) 37 (37.4) Upper respiratory tract infection 20 (10.1) 8 (8.1) Bronchiolitis 9 (4.5) 9 (9.1) Cough 5 (2.5) 4 (4.0) Bronchitis 3 (1.5) 3 (3.0) Diarrhoea 2 (1.0) 4 (4.0) Diarrhoea infectious 3 (1.5) 3 (3.0) Viral infection 4 (2.0) 2 (2.0) Wheezing - 5 (5.1) Vomiting - 4 (4.0) Pyrexia 3 (1.5) - Conjunctivitis - 2 (2.0) Constipation 2 (1.0) - Flatulence 2 (1.0) - Gastrooesophageal reflux disease - 2 (2.0) Nasopharyngitis 2 (1.0) - Pharyngitis - 2 (2.0) Rhinitis 2 (1.0) - Rhinorrhoea 2 (1.0) - Superinfection fungal - 2 (2.0) Counting rule applied: As there were more than 30 subjects per treatment group and 3 groups, only the 10 most frequent events in each treatment group are to be listed. -: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 10 most frequent events for that group. Safety Results: Number (%) of subjects with serious adverse events reported throughout the entire study period (Total Vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs N = 199 N = 99 Subjects with any SAE(s), n (%) [n assessed by investigator as related] 9 (4.5) [0] 6 (6.1) [0] Bronchiolitis 2 (1.0) [0] 3 (3.0) [0] Diarrhoea 1 (0.5) [0] 2 (2.0) [0] Superinfection fungal 1 (0.5) [0] 2 (2.0) [0] Gastrooesophageal reflux disease 1 (0.5) [0] 1 (1.0) [0]

7 Autoimmune thrombocytopenia 1 (0.5) [0] 0 (0.0) [0] Coagulopathy 1 (0.5) [0] 0 (0.0) [0] Convulsion 1 (0.5) [0] 0 (0.0) [0] Diarrhoea infectious 1 (0.5) [0] 0 (0.0) [0] Febrile convulsion 1 (0.5) [0] 0 (0.0) [0] Hydronephrosis 1 (0.5) [0] 0 (0.0) [0] Kawasaki s disease 1 (0.5) [0] 0 (0.0) [0] Oral candidiasis 0 (0.0) [0] 1 (1.0) [0] Upper respiratory tract infection 1 (0.5) [0] 0 (0.0) [0] Urinary tract infection 0 (0.0) [0] 1 (1.0) [0] Viral infection 0 (0.0) [0] 1 (1.0) [0] Fatal SAEs N = 199 N = 99 Subjects with fatal SAE(s), n (%) [n assessed by investigator as related] 0 (0.0) [0] 0 (0.0) [0] Conclusion: During the 31-day follow up period, across doses, 32 (16.2%) subjects in the 10Pn-Hexa group and 9 (9.1%) subjects in the Hexa group reported grade 3 symptoms (solicited and/or unsolicited). During the 31-day follow-up period after each vaccination, at least one unsolicited AE was reported for 57 (28.6%) subjects in the and for 37 (37.4%) in the. Throughout the study period, SAEs were reported for 9 (4.5%) subjects in the and for 6 (6.1%) in the. None of these SAEs were assessed by the investigators to be causally related to the study vaccination. No fatal SAEs were reported during the entire study period. Publications: Tran NH et al. Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants. Abstract presented at the ICID, Bangkok, Thailand, June 13-16, Date updated: 05-July-2012