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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.: (MenACWY-TT-021 BST: Mencevax ACWY-004) Title: Immunogenicity and safety study of GSK Biologicals meningococcal vaccine GSK administered in healthy subjects either previously primed with Mencevax ACWY or naïve to meningococcal vaccination. Nimenrix - GSK (MenACWY-TT): GlaxoSmithKline (GSK) Biologicals meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine Mencevax ACWY (MenPS): GSK Biologicals meningococcal serogroups A, C, W-135 and Y plain polysaccharide vaccine Rationale: The aim of the study was to evaluate the immunogenicity and safety of MenACWY-TT vaccine when administered to subjects 4.5 through 34 years of age either previously primed with MenPS vaccine in study (Mencevax ACWY-004) or not previously vaccinated with a meningococcal serogroup A,C,W-135, and/or Y vaccine. Phase: II Study Period: 19 May 2008 to 21 May 2009 [end of extended safety follow-up (ESFU) phase] Study Design: Open, controlled, non-randomized (3:1), single-centre study with 2 parallel groups. Centre: 1 centre in Lebanon. Indication: Booster immunization against Neisseria meningitidis serogroups A, C, W-135 and Y in healthy subjects 4.5 through 34 years previously vaccinated against serogroups A, C, W-135 and Y with a meningococcal polysaccharide vaccine or one dose immunization against Neisseria meningitidis serogroups A, C, W-135 and Y in healthy subjects 4.5 through 34 years naïve to meningococcal vaccination. Treatment: The study groups were as follows: : subjects previously primed with MenPS vaccine in study no: subjects not previously (or not in the preceding 10 years) vaccinated with a meningococcal plain polysaccharide vaccine or never vaccinated with a meningococcal conjugate vaccine During this study, all subjects received 1 dose of MenACWY-TT vaccine administered intramuscularly in the deltoid muscle of the non-dominant arm. Objectives: One month after MenACWY-TT vaccination: To evaluate the immunogenicity of the MenACWY-TT vaccine when given between 30 and 42 months after a priming dose of MenPS vaccine (previously administered to healthy subjects at ages 2 30 years) compared to the immunogenicity of the MenACWY-TT vaccine in age-strata matched subjects who have not previously received (or not received within the preceding 10 years) any meningococcal vaccine. Primary Outcome/Efficacy Variable: Immunogenicity: In all subjects, one month post-vaccination Meningococcal serum bactericidal assay using baby rabbit complement (rsba) titers Secondary Outcome/Efficacy Variable(s): Immunogenicity: In all subjects, prior to and one month post-vaccination, unless previously defined as primary outcome variable: meningococcal rsba titers anti-meningococcal polysaccharide (anti-ps) antibody concentrations anti-tetanus toxoid (anti-tt) antibody concentrations vaccine response to meningococcal antigens* * Vaccine response for meningococcal antigens was defined as: For initially seronegative subjects (antibody titer <1:8): post-vaccination antibody titer 1:32 For initially seropositive subjects (antibody titer 1:8): post-vaccination antibody titer 4-fold the pre-vaccination antibody titer Safety For all subjects after MenACWY-TT vaccination: Occurrence of solicited local and general symptoms during the 4-day (Day 0 - Day 3) period after vaccination. Occurrence of unsolicited symptoms up to one month after vaccination. Occurrence throughout the entire study (Day 0 Study Month 6) of serious adverse events (SAEs) and/or specific adverse events included rash (e.g. hives, idiopathic thrombocytopenia purpura, petechiae), new onset of chronic

2 illness(es) (NOCIs) (e.g. autoimmune disorders, asthma, type I diabetes and allergies), conditions prompting Emergency Room (ER) visits and any events related to lack of vaccine efficacy (i.e. meningococcal disease)*. * Events related to lack of vaccine efficacy (i.e. meningococcal disease) were recorded, but because such events were life threatening and were thus reported as SAEs, these events were not analyzed or reported separately. Statistical Methods: The analyses were done on the Total Vaccinated cohort, the According-to-protocol (ATP) cohort for persistence and the ATP cohort for immunogenicity. The Total Vaccinated cohort included all vaccinated subjects. The ATP cohort for persistence included all subjects who participated in study , who had received 1 dose of the study vaccine, for whom the administration site of the study vaccine was known, who had not received a vaccine not specified or forbidden in the protocol during the study and for whom assay results were available for antibodies against at least one study vaccine antigen component for the blood sampling taken before the administration of the MenACWY- TT dose. The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variable measures were available. This cohort included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component from the blood sample taken one month after vaccination. Analysis of immunogenicity The analysis was based on the ATP cohort for persistence and the ATP cohort for immunogenicity. For the, prior to and one month after vaccination in study , and for each vaccine group, prior to and one month after vaccination in the current study, for each antibody assessed at the corresponding time point, percentage of subjects with rsba titers above or equal to the specified cut-offs, geometric mean titers (GMTs)/geometric mean concentrations (GMCs) with 95% confidence intervals (CIs) were tabulated. Vaccine response rates to meningococcal antigens with exact 95% CIs were also calculated. Analysis of safety The analysis was based on the Total Vaccinated cohort. The percentages of subjects with at least one local/general solicited symptom during the 4-day (Days 0-3) period after vaccination were tabulated with exact 95% CI by vaccine group. The same tabulations were performed for grade 3 symptoms and for general symptoms assessed by the investigator as related to vaccination. The percentages of subjects with at least one report of unsolicited adverse event (AE) classified by Medical Dictionary for Regulatory Activities (MedDRA) preferred terms and reported up to 30 days after vaccination were tabulated. The percentages of subjects who experienced rash, NOCIs and conditions prompting ER visits from vaccination up to study end were tabulated by vaccine group. SAEs reported from vaccination up to study end were also tabulated according to MedDRA preferred terms. Study Population: Healthy males and females aged 4.5 to 34 years who previously completed routine childhood vaccinations, without history of meningococcal disease or previous vaccination with tetanus toxoid within 30 days, and who did not receive any vaccine against meningococcal disease after completion of study (Mencevax ACWY-004) (for the ) or had not previously received (or had not received within the preceding 10 years) any meningococcal vaccine (for the no). Written informed consent was obtained from each subject or subject s parents/guardians before study start (for all children of 7 years of age and above an assent was collected in addition to the consent provided by the parents/guardians). Number of Subjects no Planned, N Randomized, N (Total Vaccinated cohort) Completed (Active phase - 1 month after vaccination), n (%) 183 (95.3) 79 (100) Total Number Subjects Withdrawn, n (%) 9 (4.7) 0 (0.0) Withdrawn due to AEs, n (%) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy n (%) Not applicable Not applicable Withdrawn for other reasons n (%) 9 (4.7) 0 (0.0) Demographics no N (Total Vaccinated cohort) Females: Males 91:101 41:38 Mean Age, years (SD) 14.1 (6.79) 14.2 (7.23)

3 White - Arabic/North African heritage, n (%) 192 (100) 77 (97.5) Primary Efficacy Results: Percentage of subjects with rsba titers equal to or above the cut-off values of 1:8 and 1:128 and GMTs (ATP cohort for immunogenicity) 1:8* 1:128 GMT 95% CI 95% CI 95% CI Antibody Group Timing N n % LL UL n % LL UL value LL UL rsba- MenA rsba- MenC rsba- MenW- 135 rsba- MenY MPS Pre-ACWY-TT Post-ACWY-TT* nomps Pre-ACWY-TT Post-ACWY-TT* MPS Pre-ACWY-TT Post-ACWY-TT* nomps Pre-ACWY-TT Post-ACWY-TT* MPS Pre-ACWY-TT Post-ACWY-TT* nomps Pre-ACWY-TT Post-ACWY-TT* MPS Pre-ACWY-TT Post-ACWY-TT* nomps Pre-ACWY-TT Post-ACWY-TT* GMT = geometric mean antibody titer calculated on all subjects n/% = number/percentage of subjects with titer within the specified range Post-ACWY-TT = Post-vaccination blood sample at Month 1 *Primary outcome variable Secondary Outcome Variables: Percentage of subjects with rsba titres equal to or above the cut-off values of 1:8 and 1:128 and GMTs in the (ATP cohort for persistence) Antibody Timing N 1:8 1:128 GMT n % 95% CI n % 95% CI Value 95% CI LL UL LL UL LL UL rsba-mena Pre-MPS Post-MPS Pre-ACWY-TT rsba-menc Pre-MPS Post-MPS Pre-ACWY-TT rsba-menw-135 Pre-MPS Post-MPS Pre-ACWY-TT rsba-meny Pre-MPS Post-MPS Pre-ACWY-TT GMT = geometric mean antibody titer calculated on all subjects n/% = number/percentage of subjects with titer within the specified range Pre-MPS = Pre-vaccination blood sample in study at Month 0 Post-MPS = Post-vaccination blood sample in study at Month 1

4 Secondary Outcome Variables: Percentage of subjects with anti-ps concentrations equal to or above the cut-off values of 0.3 and 2.0 µg/ml and GMCs in the MPS group (ATP cohort for persistence) Antibody Timing N 0.3 µg/ml 2.0 µg/ml GMC (µg/ml) n % 95% CI n % 95% CI Value 95% CI LL UL LL UL LL UL Anti-PSA Pre-MPS Post-MPS Pre-ACWY-TT Anti-PSC Pre-MPS Post-MPS Pre-ACWY-TT Anti-PSW-135 Pre-MPS Post-MPS Pre-ACWY-TT Anti-PSY Pre-MPS Post-MPS Pre-ACWY-TT GMC = geometric mean antibody concentration calculated on all subjects n/% = number/percentage of subjects with concentration within the specified range Pre-MPS = Pre-vaccination blood sample in study at Month 0 Post-MPS = Post-vaccination blood sample in study at Month 1 Secondary Outcome Variables: Percentage of subjects with anti-ps concentrations equal to or above the cut-off values of 0.3 µg/ml and 2.0 µg/ml and GMCs (ATP cohort for immunogenicity) 0.3 µg/ml 2.0 µg/ml GMC (µg/ml) 95% CI 95% CI 95% CI Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-PSA MPS Pre-ACWY-TT Post-ACWY-TT nomps Pre-ACWY-TT Post-ACWY-TT Anti-PSC MPS Pre-ACWY-TT Post-ACWY-TT nomps Pre-ACWY-TT Post-ACWY-TT Anti-PSW- 135 MPS Pre-ACWY-TT Post-ACWY-TT nomps Pre-ACWY-TT Post-ACWY-TT Anti-PSY MPS Pre-ACWY-TT Post-ACWY-TT nomps Pre-ACWY-TT Post-ACWY-TT GMC = geometric mean antibody concentration calculated on all subjects n/% = number/percentage of subjects with concentration within the specified range Post-ACWY-TT = Post-vaccination blood sample at Month 1 Secondary Outcome Variables: Percentage of subjects with anti-tt concentrations equal to or above the cut-off values of 0.1 IU/mL and 1.0 IU/mL and GMCs (ATP cohort for immunogenicity) 0.1 IU/mL 1.0 IU/mL GMC (IU/mL) 95% CI 95% CI 95% CI

5 Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-TT MPS Pre-ACWY-TT Post-ACWY-TT nomps Pre-ACWY-TT Post-ACWY-TT GMC = geometric mean antibody concentration calculated on all subjects n/% = number/percentage of subjects with concentration within the specified range Post-ACWY-TT = Post-vaccination blood sample at Month 1 Secondary Outcome Variables: Vaccine response for rsba antibodies one month after vaccination (ATP cohort for immunogenicity) Vaccine Response 95% CI Antibody Group Pre-vaccination status N n % LL UL rsba-mena MPS S S Total nomps S S Total rsba-menc MPS S S Total nomps S S Total rsba-menw-135 MPS S S Total nomps S S Total rsba-meny MPS S S Total nomps S S Total S- = initially seronegative subjects (antibody titer < 1:8) prior to vaccination S+ = initially seropositive subjects (antibody titer 1:8) prior to vaccination Total = subjects either seropositive or seronegative at pre-vaccination Vaccine response defined as: For initially seronegative subjects: post-vaccination antibody titer 1:32 For initially seropositive subjects: post-vaccination antibody titer 4-fold the pre-vaccination antibody titer N = number of subjects with both pre- and post-vaccination results available n/% = number/percentage of responders 95% CI = exact 95% confidence interval; LL = lower limit; UL = upper limit Secondary Outcome Variables: Number (%) of subjects with solicited local symptoms reported during the 4-day (Days 0 3) post-vaccination period (Total Vaccinated cohort) no 95% CI 95% CI Symptom Intensity N n % LL UL N n % LL UL Pain Any

6 Grade Redness Any > 50 mm Swelling Any > 50 mm N = number of subjects with the 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 = occurrence of any local symptoms regardless of their intensity grade Grade 3 = pain that prevented normal activity Secondary Outcome Variables: Number (%) of subjects with solicited general symptoms reported during the 4-day (Days 0 3) post-vaccination period (Total Vaccinated cohort) no 95% CI 95% CI Symptom Intensity/ N n % LL UL N n % LL UL Relationship Fatigue Any Grade Related Fever (oral temperature) Gastrointestinal Symptoms 37.5 C > 39.5 C Related Any Grade Related Headache Any Grade Related N = number of subjects with the documented dose n/% = number/percentage of subjects reporting the symptom at least once 95%CI = Exact 95% confidence interval; LL = lower limit Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination Grade 3 = general symptoms that prevented normal activities Related = general symptoms assessed by the investigator as causally related to the study vaccination Secondary Outcome Variables: Number (%) of subjects reporting rash from the day of the vaccination up to study end (Total Vaccinated cohort) Rash no Subjects with any rash, n (%) 0 (0.0) 0 (0.0) Secondary Outcome Variables: Number (%) of subjects reporting NOCIs from the day of the vaccination up to study end (Total Vaccinated cohort) New Onset of Chronic Illness(es) no Subjects with any NOCI(s), n (%) 0 (0.0) 2 (2.5) Seasonal allergy - 1 (1.3) Rhinitis - 1 (1.3) -: NOCI absent Secondary Outcome Variables Number (%) of subjects reporting AEs resulting in ER visits from the day of the vaccination up to study end (Total Vaccinated cohort) Emergency Room Visit no Subjects with any ER visit(s), n (%) 0 (0.0) 1 (1.3) Road traffic accident - 1 (1.3) -: ER visit absent Safety results: Number (%) of subjects with unsolicited AEs during the 31-day post-vaccination period (Total Vaccinated

7 cohort) Most frequent adverse events - On-Therapy (occurring within Days 0-30 following vaccination) no Subjects with any AE(s), n (%) 19 (9.9) 11 (13.9) Tonsillitis 4 (2.1) 4 (5.1) Dizziness 6 (3.1) - Urinary tract infection 1 (0.5) 1 (1.3) Abdominal pain - 1 (1.3) Back pain 1 (0.5) - Cough - 1 (1.3) Decreased appetite 1 (0.5) - Ear pain 1 (0.5) - Excoriation 1 (0.5) - Headache 1 (0.5) - Influenza - 1 (1.3) Local swelling 1 (0.5) - Nasopharyngitis 1 (0.5) - Neck pain 1 (0.5) - Ocular hyperaemia - 1 (1.3) Oropharyngeal pain - 1 (1.3) Pain 1 (0.5) - Pallor 1 (0.5) - Pyrexia 1 (0.5) - Rhinitis - 1 (1.3) Rhinorrhoea 1 (0.5) - Road traffic accident - 1 (1.3) Seasonal allergy - 1 (1.3) Tendon rupture 1 (0.5) - - : Adverse Event absent. Safety results: Number (%) of subjects with SAEs from the day of the vaccination up to study end (Total Vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs no Subjects with any SAE(s), n (%) [n assessed by investigator as 1 (0.5) [0] 0 (0.0) [0] related] Tendon rupture 1 (0.5) [0] 0 (0.0) [0] Fatal SAEs no Subjects with fatal SAE(s), n (%) [n assessed by investigator as related] 0 (0.0) [0] 0 (0.0) [0] Conclusion: One month after the vaccination, all subjects in both MPS and nomps groups had rsba titers 1:8 for the 4 meningococcal serogroups. During the 31-day post-vaccination period, 19 (9.9%) subjects in the and 11 (13.9%) subjects in the NoMPS Group reported at least one unsolicited adverse event. During the entire study period, 1 non-fatal SAE of tendon rupture was reported in 1 subject from the ; it was assessed by the investigator as not related to the study vaccination. Publications: Dbaibo G et al. One dose of the meningococcal tetravalent tetanus toxoid conjugated vaccine (MenACWY-TT) is immunogenic with an acceptable safety profile in unvaccinated subjects and those previously vaccinated with a MenACWY polysaccharide vaccine. Abstract presented at the 3 rd Northern European Conference on Travel Medicine (NECTM). Hamburg, Germany, May 2010.

8 Dbaibo G et al. (2012) The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine. Int J Infect Dis. 16(8): Date updated: 16-October-2012