Leaflet NIMENRIX powder+solvent for solution for injection in pre-filled syringe

Nimenrix powder and solvent for solution for injection in pre-filled syringe

Meningococcal groups A, C, W-135 and Y conjugate vaccine

After reconstitution, 1 dose (0.5 ml) contains:

Neisseria meningitidis group A polysaccharide1 5 micrograms

Neisseria meningitidis group C polysaccharide1 5 micrograms

Neisseria meningitidis group W-135 polysaccharide1 5 micrograms

Neisseria meningitidis group Y polysaccharide1 5 micrograms1conjugated to tetanus toxoid carrier protein 44 micrograms

For the full list of excipients, see section 6.1.

Powder and solvent for solution for injection.

The powder or cake is white.

The solvent is clear and colourless.

Nimenrix is indicated for active immunisation of individuals from the age of 6 weeks against invasivemeningococcal disease caused by Neisseria meningitidis groups A, C, W-135, and Y.

Nimenrix should be used in accordance with available official recommendations.

Infants from 6 weeks to less than 6 months of age: two doses, each of 0.5 ml, should be administeredwith an interval of 2 months between doses.

Infants from 6 months of age, children, adolescents and adults: a single 0.5 mL dose should beadministered.

An additional primary dose of Nimenrix may be considered appropriate for some individuals (seesection 4.4).

Long-term antibody persistence data following vaccination with Nimenrix are available up to 10 yearsafter vaccination (see sections 4.4 and 5.1).

After completion of the primary immunisation course in infants 6 weeks to less than 12 months of age,a booster dose should be given at 12 months of age with an interval of at least 2 months after the last

Nimenrix vaccination (see section 5.1).

In previously vaccinated individuals 12 months of age and older, Nimenrix may be given as a boosterdose if they have received primary vaccination with a conjugated or plain polysaccharidemeningococcal vaccine (see sections 4.4 and 5.1).

Immunisation should be carried out by intramuscular injection only.

In infants, the recommended injection site is the anterolateral aspect of the thigh. In individuals from1 year of age, the recommended injection site is the anterolateral aspect of the thigh or the deltoidmuscle (see sections 4.4 and 4.5).

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

Nimenrix should under no circumstances be administered intravascularly, intradermally orsubcutaneously.

It is good clinical practice to precede vaccination by a review of the medical history (especially withregard to previous vaccination and possible occurrence of undesirable effects) and a clinicalexamination.

Appropriate medical treatment and supervision should always be readily available in case of a rareanaphylactic event following the administration of the vaccine.

Vaccination with Nimenrix should be postponed in subjects suffering from an acute severe febrileillness. The presence of a minor infection, such as a cold, should not result in the deferral ofvaccination.

Syncope (fainting) can occur following, or even before, any vaccination especially in adolescents asa psychogenic response to the needle injection. This can be accompanied by several neurologicalsigns such as transient visual disturbance, paraesthesia and tonic-clonic limb movements duringrecovery. It is important that procedures are in place to avoid injury from faints.

Nimenrix should be given with caution to individuals with thrombocytopenia or any coagulationdisorder since bleeding may occur following an intramuscular administration to these subjects.

Immunodeficiency

It may be expected that in patients receiving immunosuppressive treatment or patients withimmunodeficiency, an adequate immune response may not be elicited.

Persons with familial complement deficiencies (for example, C5 or C3 deficiencies) and personsreceiving treatments that inhibit terminal complement activation (for example, eculizumab) are atincreased risk for invasive disease caused by Neisseria meningitidis groups A, C, W-135 and Y, evenif they develop antibodies following vaccination with Nimenrix.

Nimenrix will only confer protection against Neisseria meningitidis groups A, C, W-135 and Y. Thevaccine will not protect against any other Neisseria meningitidis groups.

A protective immune response may not be elicited in all vaccinees.

Subjects previously vaccinated with a plain polysaccharide meningococcal vaccine and vaccinatedwith Nimenrix 30 to 42 months later had lower Geometric Mean Titres (GMTs) measured with aserum bactericidal assay using rabbit complement (rSBA) than subjects who had not been vaccinatedwith any meningococcal vaccine in the preceding 10 years (see section 5.1). The clinical relevance ofthis observation is unknown.

The safety and immunogenicity of Nimenrix was evaluated when it was sequentially administered orco-administered with a vaccine containing, diphtheria and tetanus toxoids, acellular pertussis,inactivated polioviruses (1, 2 and 3), hepatitis B surface antigen and Haemophilus influenzae type bpolyribosyl ribose phosphate conjugated to tetanus toxoid (DTaP-HBV-IPV/Hib) in the second year oflife. The administration of Nimenrix one month after the DTaP-HBV-IPV/Hib vaccine resulted inlower rSBA GMTs against groups A, C and W-135 compared with co-administration (see section 4.5).

The clinical relevance of this observation is unknown.

A single dose administered at 6 months was associated with lower human complement serumbactericidal assay (hSBA) titres to groups W-135 and Y compared with three doses administered at 2,4, and 6 months (see section 5.1). The clinical relevance of this observation is unknown. If an infantaged 6 months to less than 12 months is expected to be at particular risk of invasive meningococcaldisease due to exposure to groups W-135 and/or Y, consideration may be given to administering asecond primary dose of Nimenrix after an interval of 2 months.

Toddlers aged 12-14 months had similar rSBA titres to groups A, C, W-135 and Y at one month afterone dose of Nimenrix or at one month after two doses of Nimenrix given two months apart.

A single dose was associated with lower hSBA titres to groups W-135 and Y compared with twodoses given two months apart. Similar responses to groups A and C were observed after one or twodoses (see section 5.1). The clinical relevance of this observation is unknown. If a toddler is expectedto be at particular risk of invasive meningococcal disease due to exposure to groups W-135 and/or Y,consideration may be given to administering a second dose of Nimenrix after an interval of 2 months.

Regarding waning of antibody against group A or group C after a first dose of Nimenrix in childrenaged 12-23 months, see under Persistence of serum bactericidal antibody titres.

Following administration of Nimenrix there is a waning of serum bactericidal antibody titres againstgroup A when using hSBA (see section 5.1). The clinical relevance of this observation is unknown.

However, if an individual is expected to be at particular risk of exposure to group A and received adose of Nimenrix more than approximately one year previously, consideration may be given toadministering a booster dose.

A decline in antibody titres over time has been observed for groups A, C, W-135 and Y. The clinicalrelevance of this observation is unknown. A booster dose might be considered in individualsvaccinated at toddler age remaining at high risk of exposure to meningococcal disease caused bygroups A, C, W-135 or Y (see section 5.1).

Although an increase of the anti-tetanus toxoid (TT) antibody concentrations was observed followingvaccination with Nimenrix, Nimenrix does not substitute for tetanus immunisation.

Giving Nimenrix with or one month before a TT-containing vaccine in the second year of life does notimpair the response to TT or significantly affect safety. No data are available beyond the age of2 years.

This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially‘sodium-free’.

In infants, Nimenrix can be given concomitantly with combined DTaP-HBV-IPV/Hib vaccines andwith 10-valent pneumococcal conjugate vaccine.

From age 1 year and above, Nimenrix can be given concomitantly with any of the following vaccines:hepatitis A (HAV) and hepatitis B (HBV) vaccines, measles - mumps - rubella (MMR) vaccine,measles - mumps - rubella - varicella (MMRV) vaccine, 10-valent pneumococcal conjugate vaccine orunadjuvanted seasonal influenza vaccine.

In the second year of life, Nimenrix can also be given concomitantly with combined diphtheria -tetanus - acellular pertussis (DTaP) vaccines, including combination DTaP vaccines with hepatitis B,inactivated poliovirus or Haemophilus influenzae type b (HBV, IPV or Hib) such as DTaP-HBV-

IPV/Hib vaccine, and 13-valent pneumococcal conjugate vaccine.

In individuals aged 9 to 25 years, Nimenrix can be given concomitantly with human papillomavirusbivalent [Type 16 and 18] vaccine, recombinant (HPV2).

Whenever possible, Nimenrix and a TT-containing vaccine, such as DTaP-HBV-IPV/Hib vaccine,should be co-administered or Nimenrix should be administered at least one month before the TT-containing vaccine.

One month after co-administration with a 10-valent pneumococcal conjugate vaccine, lower

Geometric Mean antibody Concentrations (GMCs) and opsonophagocytic assay (OPA) antibody

GMTs were observed for one pneumococcal serotype (18C conjugated to tetanus toxoid carrierprotein). The clinical relevance of this observation is unknown. There was no impact ofco-administration on immune responses to the other nine pneumococcal serotypes.

One month after co-administration with a combined tetanus toxoid, reduced diphtheria toxoid andacellular pertussis vaccine, adsorbed (Tdap) in subjects aged 9 to 25 years, lower GMCs wereobserved to each pertussis antigen (pertussis toxoid [PT], filamentous haemagglutinin [FHA] andpertactin [PRN]). More than 98% of subjects had anti-PT, FHA or PRN concentrations above theassay cut-off thresholds. The clinical relevance of these observations is unknown. There was noimpact of co-administration on immune responses to Nimenrix or the tetanus or diphtheria antigensincluded in Tdap.

If Nimenrix is to be given at the same time as another injectable vaccine, the vaccines should alwaysbe administered at different injection sites.

It may be expected that in patients receiving immunosuppressive treatment, an adequate response maynot be elicited.

There is limited experience with use of Nimenrix in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,embryo/foetal development, parturition or post-natal development (see section 5.3).

Nimenrix should be used during pregnancy only when clearly needed, and the possible advantagesoutweigh the potential risks for the foetus.

It is unknown whether Nimenrix is excreted in human milk.

Nimenrix should only be used during breast-feeding when the possible advantages outweigh thepotential risks.

Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

No studies on the effects of Nimenrix on the ability to drive and use machines have been performed.

However, some of the effects mentioned under section 4.8 “Undesirable effects” may affect the abilityto drive or use machines.

The safety of Nimenrix presented in the table below is based on two clinical study datasets as follows:

- A pooled analysis of data from 9,621 subjects administered a single dose of Nimenrix. This totalincluded 3,079 toddlers (12 months to 23 months), 909 children between 2 and 5 years of age,990 children between 6 and 10 years of age, 2,317 adolescents (11 to 17 years) and 2,326 adults(18 to 55 years).

- Data from a study in infants aged 6 to 12 weeks at the time of the first dose (Study

MenACWY-TT-083), 1,052 subjects received at least one dose of a primary series of 2 or 3doses of Nimenrix and 1,008 received a booster dose at approximately 12 months of age.

Safety data have also been evaluated in a separate study, in which a single dose of Nimenrix wasadministered to 274 individuals aged 56 years and older.

In the 6-12 weeks and in the 12-14 months age groups who received 2 doses of Nimenrix given2 months apart, the first and second doses were associated with similar local and systemicreactogenicity.

The local and general adverse reaction profile of a booster dose of Nimenrix given to subjects from12 months through 30 years of age after primary vaccination with Nimenrix or other conjugated orplain polysaccharide meningococcal vaccines, was similar to the local and general adverse reactionprofile observed after primary vaccination with Nimenrix, except for gastrointestinal symptoms(including diarrhoea, vomiting, and nausea), which were very common among subjects 6 years of ageand older.

Adverse reactions reported are listed according to the following frequency categories:

Very common: (≥ 1/10)

Common: (≥ 1/100 to <1/10)

Uncommon: (≥ 1/1,000 to <1/100)

Rare: (≥ 1/10,000 to <1/1,000)

Very rare: (<1/10,000)

Not known (cannot be estimated from available data)

Table 1 shows the adverse reactions reported from the studies in subjects aged from 6 weeks up to55 years of age and post-marketing experience. Adverse reactions reported in subjects aged >55 yearswere similar to those observed in younger adults.

Table 1: Tabulated summary of adverse reactions by system organ class

System Organ Class Frequency Adverse reactions

Blood and lymphatic system Not known*** Lymphadenopathydisorders

Immune system disorders Uncommon Hypersensitivity***

Not known Anaphylaxis***

Metabolism and nutrition Very common Appetite lostdisorders

Psychiatric disorders Very common Irritability

Uncommon Insomnia

Crying

Nervous system disorders Very common Drowsiness

Uncommon Hypoaesthesia

Dizziness

Rare Febrile convulsion

Gastrointestinal disorders Common Diarrhoea

Nausea*

Skin and subcutaneous tissue Uncommon Pruritusdisorders Urticaria

Rash**

Musculoskeletal and Uncommon Myalgiaconnective tissue disorders Pain in extremity

General disorders and Very common Feveradministration site conditions Swelling at injection site

Pain at injection site

Redness at injection site

Common Injection site haematoma*

Uncommon Malaise

Injection site induration

Injection site pruritus

Injection site warmth

Injection site anaesthesia

Not known*** Extensive limb swelling at the injection site,frequently associated with erythema,sometimes involving the adjacent joint orswelling of the entire injected limb

*Nausea and Injection site haematoma occurred at a frequency of Uncommon in infants

**Rash occurred at a frequency of Common in infants

***ADR identified post-marketing

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

No case of overdose has been reported.

Pharmacotherapeutic group: vaccines, meningococcal vaccines, ATC code: J07AH08

Anti-capsular meningococcal antibodies protect against meningococcal disease via complementmediated bactericidal activity. Nimenrix induces the production of bactericidal antibodies againstcapsular polysaccharides of Neisseria meningitidis groups A, C, W-135 and Y when measured byassays using either rSBA or hSBA.

In Study MenACWY-TT-083, the first dose was administered at 6 to 12 weeks of age, the second afteran interval of 2 months, and a third (booster) dose administered at approximately 12 months of age.

DTaP-HBV-IPV/Hib and a 10-valent pneumococcal vaccine were co-administered. Nimenrix elicitedrSBA and hSBA titres against the four meningococcal groups as shown in Table 2. The responseagainst group C was non-inferior to the one elicited by licensed MenC-CRM and MenC-TT vaccinesin terms of percentages with rSBA titres ≥ 8 at 1 month after the second dose.

Data from this study support the extrapolation of the immunogenicity data and posology to infantsfrom 12 weeks to less than 6 months of age.

Table 2: rSBA and hSBA titres following two doses of Nimenrix (or MenC-CRM or MenC-TT)given 2 months apart with the first dose administered to infants 6-12 weeks of age andfollowing a booster at 12 months of age (Study MenACWY-TT-083)rSBA* hSBA**

Meningo-

Vaccine Timecoccalgroup pointgroup ≥ 8 GMT ≥ 8 GMT

N N(95% CI) (95% CI) (95% CI) (95% CI)

Post- 97.4% 203 96.5% 157456 202dose 2(1) (95.4; 98.6) (182; 227) (93.0; 98.6) (131; 188)

A Nimenrix

Post- 99.6% 1561 99.5% 1007(1) 462 214booster (98.4; 99.9) (1412; 1725) (97.4;100) (836;1214)

Post- 98.7% 612 98.6% 1308456 218dose 2(1) (97.2; 99.5) (540; 693) (96.0; 99.7) (1052; 1627)

Nimenrix

Post- 99.8% 1177 99.5% 4992(1) 463 221booster (98.8; 100) (1059; 1308) (97.5; 100) (4086; 6100)

Post- 99.6% 958 100% 3188

MenC- (1) 455 202dose 2 (98.4; 99.9) (850; 1079) (98.2; 100) (2646; 3841)

C CRM

Post- 98.4% 1051 100% 5438vaccine 446 216booster(1) (96.8; 99.4) (920; 1202) (98.3; 100) (4412; 6702)

Post- 100% 1188 100% 2626

MenC- (1) 457 226dose 2 (99.2; 100) (1080; 1307) (98.4; 100) (2219; 3109)

TT

Post- 100% 1960 100% 5542vaccine 459 219booster(1) (99.2; 100) (1776; 2163) (98.3; 100) (4765; 6446)

Post- 99.1% 1605 100% 753(1) 455 217dose 2 (97.8; 99.8) (1383; 1862) (98.3; 100) (644; 882)

W Nimenrix

Post- 99.8% 2777 100% 5123(1) 462 218booster (98.8; 100) (2485; 3104) (98.3; 100) (4504; 5826)

Post- 98.2% 483 97.7% 328456 214dose 2(1) (96.6; 99.2) (419; 558) (94.6; 99.2) (276; 390)

Y Nimenrix

Post- 99.4% 881 100% 2954462 217booster(1) (99.1; 99.9) (787; 986) (98.3; 100) (2498; 3493)

The analysis of immunogenicity was conducted on the primary according-to-protocol (ATP) cohort.

*rSBA analysis performed at Public Health England (PHE) laboratories in UK

**hSBA analysis performed at GSK laboratories(1) blood sampling performed 21 to 48 days post vaccination

In Study MenACWY-TT-087, infants received either a single primary dose at 6 months followed by abooster dose at 15-18 months (DTaP-IPV/Hib and 10-valent pneumococcal conjugate vaccine wasco-administered at both vaccination time points) or three primary doses at 2, 4, and 6 months followedby a booster dose at 15-18 months. A single primary dose administered at 6 months of age elicitedrobust rSBA titres to the four meningococcal groups, as measured by the percentage of subjects withrSBA titres ≥ 8, that were comparable to responses after the last dose of a three-dose primary series. Abooster dose produced robust responses, comparable between the two dosing groups, against all fourmeningococcal groups. Results are shown in Table 3.

Table 3: rSBA and hSBA titres following a single dose of Nimenrix in infants at 6 months of ageand pre-and post-booster at 15-18 months of age (Study MenACWY-TT-087)

Meningo- rSBA* hSBA**

Timecoccalpointgroup ≥ 8 GMT ≥ 8 GMT

N N(95% CI) (95% CI) (95% CI) (95% CI)

Post-dose 98.8% 1333 98.3% 271(1) 163 591 (95.6; 99.9) (1035; 1716) (90.9; 100) (206; 355)

Pre- 81.7% 125 66.2% 20.8

A 131 71booster (74; 87.9) (84.4; 186) (54; 77) (13.5; 32.2)

Post- 99.3% 2762 100% 1416139 83booster (1) (96.1; 100) (2310; 3303) (95.7; 100) (1140; 1758)

Post-dose 99.4% 592 100% 5231(1) 163 66(96.6; 100) (482; 726) (94.6;100) (382; 717)

Pre- 65.6% 27.4 96.2% 151

C 131 78booster (56.9; 73.7) (20.6; 36.6) (89.2; 99.2) (109; 210)

Post- 99.3% 2525 100% 13360139 92booster (1) (96.1; 100) (2102; 3033) (96.1; 100) (10953; 16296)

Post-dose 93.9% 1256 87.2% 1371(1) 163 47(89; 97) (917; 1720) (74.3; 95.2) (78.4; 238)

W Pre- 77.9% 63.3 100% 429131 53booster (69.8; 84.6) (45.6; 87.9) (93.3; 100) (328; 559)

Post- 100% 3145 100% 9016(1) 139 59booster (97.4; 100) (2637; 3750) (93.9; 100) (7045; 11537)

Post-dose 98.8% 1470 92.3% 1951(1) 163 52(95.6; 99.9) (1187; 1821) (81.5; 97.9) (118; 323)

Pre- 88.5% 106 98.4% 389

Y 131 61booster (81.8; 93.4) (76.4; 148) (91.2; 100) (292; 518)

Post- 100% 2749 100% 5978(1) 139 69booster (97.4; 100) (2301; 3283) (94.8; 100) (4747; 7528)

The analysis of immunogenicity was conducted on the primary ATP cohort.

*rSBA analysis performed at PHE laboratories in UK

**hSBA analysis performed at Neomed in Canada(1) blood sampling performed 1 month post vaccination

Measurement of hSBA titres was a secondary endpoint in Study MenACWY-TT-087. Althoughsimilar responses to groups A and C were observed with both dosing schedules, a single primary dosein infants at 6 months was associated with lower hSBA titres to groups W-135 and Y as measured bythe percentage of subjects with hSBA titres ≥ 8 [87.2% (95% CI: 74.3, 95.2) and 92.3% (95% CI:81.5, 97.9), respectively] compared with three primary doses at 2, 4, and 6 months of age [100% (95%

CI: 96.6, 100) and 100% (95% CI: 97.1, 100), respectively] (see section 4.4). After a booster dose,hSBA titres to all four meningococcal groups were comparable between the two dosing schedules.

Results are shown in Table 3.

In clinical studies MenACWY-TT-039 and MenACWY-TT-040, a single dose of Nimenrix elicited

SBA titres against the four meningococcal groups, with group C rSBA titres that were comparable tothose elicited by a licensed MenC-CRM vaccine in terms of the percentage of subjects with rSBAtitres ≥ 8. In Study MenACWY-TT-039, hSBA was also measured as a secondary endpoint. Resultsare shown in Table 4.

Table 4: SBA* titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged12-23 months (Studies MenACWY-TT-039/040)

Study MenACWY-TT-039(1) Study MenACWY-TT-040(2)

Meningo

Vaccine rSBA* hSBA* rSBA*

- coccalgroup ≥ 8 GMT ≥ 8 GMT ≥ 8 GMTgroup N N N(95% CI) (95% CI) (95% CI) (95% CI) (95% CI) (95% CI)99.7% 2205 77.2% 19.0 98.4% 3170

A Nimenrix 354 338 183(98.4; 100) (2008; 2422) (72.4; 81.6) (16.4; 22.1) (95.3; 99.7) (2577; 3899)99.7% 478 98.5% 196 97.3% 829

Nimenrix 354 341 183(98.4; 100) (437; 522) (96.6; 99.5) (175; 219) (93.7; 99.1) (672; 1021)

C

MenC-CRM 97.5% 212 81.9% 40.3 98.2% 691121 116 114vaccine (92.9; 99.5) (170; 265) (73.7; 88.4) (29.5; 55.1) (93.8; 99.8) (521; 918)100% 2682 87.5% 48.9 98.4% 4022

W-135 Nimenrix 354 336 186(99.0; 100) (2453; 2932) (83.5 ; 90.8) (41.2; 58.0) (95.4; 99.7) (3269; 4949)100% 2729 79.3% 30.9 97.3% 3168

Y Nimenrix 354 329 185(99.0; 100) (2473; 3013) (74.5; 83.6) (25.8; 37.1) (93.8; 99.1) (2522; 3979)

The analysis of immunogenicity was conducted on the ATP cohorts.(1) blood sampling performed 42 to 56 days post vaccination(2) blood sampling performed 30 to 42 days post vaccination

*SBA analyses performed at GSK laboratories

Long-term immunogenicity in toddlers

Study MenACWY-TT-104 evaluated the immunogenicity after 1 month and the persistence of theresponse up to 5 years following 1 or 2 doses (given 2 months apart) of Nimenrix in toddlers aged12 to 14 months. One month following one or two doses Nimenrix elicited rSBA titres against all fourmeningococcal groups that were similar in terms of the percentage of subjects with rSBA titre ≥ 8 and

GMT. As a secondary endpoint hSBA titres were measured. One month post dose one or two

Nimenrix elicited hSBA titres against groups W-135 and Y that were higher in terms of the percentageof subjects with hSBA titre ≥ 8 when two doses were given compared with one (see section 4.4).

Nimenrix elicited hSBA titres against groups A and C that were similar in terms of the percentage ofsubjects with hSBA titre ≥ 8 when two doses were given compared with one. At Year 5 only a smalldifference in antibody persistence between one and two doses was observed, in terms of percentagesof subjects with hSBA titres ≥ 8 against all groups. Antibody persistence was observed at Year 5against groups C, W-135 and Y. After one and two doses the percentages of subjects with hSBA titres≥ 8 for group C were 60.7% and 67.8%, group W-135 were 58.9% and 63.6% and group Y were61.5% and 54.2%, respectively. For group A, 27.9% and 17.9% of subjects receiving one or twodoses, respectively, had hSBA titres ≥ 8. Results are shown in Table 5.

Table 5: rSBA and hSBA titres following one or two doses of Nimenrix with the first doseadministered to toddlers aged 12-14 months and persistence up to 5 years (Study

MenACWY-TT-104)

Meningo- Nimenrix rSBA* hSBA**

Timecoccal dose (1) ≥ 8 GMT ≥ 8 GMTpoint N Ngroup group (95% CI) (95% CI) (95% CI) (95% CI)97.8% 1437 95.9% 118

Post dose 1 180 74(94.4; 99.4) (1118; 1847) (88.6; 99.2) (86.8; 161)63.5% 62.7 35.1% 6.1

Year 1 167 70(55.7; 70.8) (42.6; 92.2) (25.9; 49.5) (4.1; 8.9)1 dose46.9% 29.7 36.4% 5.8

Year 3 147 55(38.7; 55.3) (19.8; 44.5) (23.8; 50.4) (3.8; 8.9)58.6% 46.8 27.9% 4.4

Year 5 133 61(49.8; 67.1) (30.7; 71.5) (17.1; 40.8) (3.1; 6.2)96.8% 1275 97.0% 133

A Post dose 1 158 66(92.8; 99.0) (970; 1675) (89.5; 99.6) (98.1; 180)98.0% 1176 97.0% 170

Post dose 2 150 66(94.3; 99.6) (922; 1501) (89.5; 99.6) (126; 230)70.6% 76.6 35.5% 6.42 doses Year 1 143 62(62.4; 77.9) (50.7; 115.7) (23.7; 48.7) (4.2; 10.0)54.5% 28.5 36.0% 5.4

Year 3 121 50(45.2; 63.6) (18.7; 43.6) (22.9; 50.8) (3.6; 8.0)65.8% 69.9 17.9% 3.1

Year 5 117 56(56.5; 74.3) (44.7; 109.3) (8.9; 30.4) (2.4; 4.0)95.0% 452 98.7% 152

Post dose 1 179 78(90.7; 97.7) (346; 592) (93.1; 100) (105; 220)49.1% 16.2 81.7% 35.2

Year 1 167 71(41.3; 56.9) (12.4; 21.1) (70.7; 89.9) (22.5; 55.2)1 dose35.4% 9.8 65.6% 23.6

Year 3 147 61(27.7; 43.7) (7.6; 12.7) (52.3; 77.3) (13.9; 40.2)20.5% 6.6 60.7% 18.1

Year 5 132 61

C (13.9; 28.3) (5.3; 8.2) (47.3; 72.9) (10.9; 30.0)95.5% 369 95.7% 161

Post dose 1 157 70(91.0; 98.2) (281; 485) (88.0; 99.1) (110; 236)98.7% 639 100% 1753

Post dose 2 150 692 doses (95.3; 99.8) (522; 783) (94.8; 100) (1278; 2404)55.2% 21.2 93.7% 73.4

Year 1 143 63(46.7; 63.6) (15.6; 28.9) (84.5; 98.2) (47.5; 113.4)33.9% 11.5 67.9% 27.0

Year 3 121 56(25.5; 43.0) (8.4; 15.8) (54.0; 79.7) (15.6; 46.8)

Meningo- Nimenrix rSBA* hSBA**

Timecoccal dosepoint(1) ≥ 8 GMT ≥ 8 GMT

N Ngroup group (95% CI) (95% CI) (95% CI) (95% CI)28.4% 8.5 67.8% 29.4

Year 5 116 59(20.5; 37.6) (6.4; 11.2) (54.4; 79.4) (16.3; 52.9)95.0% 2120 62.5% 27.5

Post dose 1 180 72(90.8; 97.7) (1601; 2808) (50.3; 73.6) (16.1; 46.8)

Year 1 65.3% 57.2 95.8% 209.0167 72(57.5; 72.5) (39.9; 82.0) (88.3; 99.1) (149.9; 291.4)1 dose59.2% 42.5 71.6% 30.5

Year 3 147 67(50.8; 67.2) (29.2; 61.8) (59.3; 82.0) (18.7; 49.6)44.4% 25.0 58.9% 20.8

Year 5 133 56(35.8; 53.2) (16.7; 37.6) (45.0; 71.9) (11.6; 37.1)

W-135 94.9% 2030 68.9% 26.2

Post dose 1 158 61(90.3; 97.8) (1511; 2728) (55.7; 80.1) (16.0; 43.0)100% 3533 97.1% 757

Post dose 2 150 70(97.6; 100) (2914; 4283) (90.1; 99.7) (550; 1041)77.6% 123 98.5% 232.6

Year 1 143 652 doses (69.9; 84.2) (82.7; 183) (91.7; 100.0) (168.3; 321.4)72.7% 92.9 87.0% 55.5

Year 3 121 54(63.9; 80.4) (59.9; 144) (75.1; 94.6) (35.3; 87.1)50.4% 37.1 63.6% 19.5

Year 5 117 44(41.0; 59.8) (23.3; 59.0) (47.8; 77.6) (10.7; 35.2)92.8% 952 67.6% 41.2

Post dose 1 180 71(88.0; 96.1) (705; 1285) (55.5; 78.2) (23.7; 71.5)73.1% 76.8 91.9% 144

Year 1 167 62(65.7; 79.6) (54.2; 109.0) (82.2; 97.3) (97.2; 214.5)1 dose61.9% 58.0 53.1% 17.3

Year 3 147 64(53.5; 69.8) (39.1; 86.0) (40.2; 65.7) (10.1; 29.6)47.4% 36.5 61.5% 24.3

Year 5 133 65

Y (38.7; 56.2) (23.6; 56.2) (48.6; 73.3) (14.3; 41.1)93.6% 933 64.3% 31.9

Post dose 1 157 56(88.6; 96.9) (692; 1258) (50.4; 76.6) (17.6; 57.9)99.3% 1134 95.3% 513

Post dose 2 150 64(96.3; 100) (944; 1360) (86.9; 99.0) (339; 775)2 doses79.7% 112.3 87.9% 143.9

Year 1 143 58(72.2; 86.0) (77.5; 162.8) (76.7; 95.0) (88.5; 233.8)68.6% 75.1 61.5% 24.1

Year 3 121 52(59.5; 76.7) (48.7; 115.9) (47.0; 74.7) (13.3; 43.8)

Meningo- Nimenrix rSBA* hSBA**

Timecoccal dosepoint(1) ≥ 8 GMT ≥ 8 GMT

N Ngroup group (95% CI) (95% CI) (95% CI) (95% CI)58.1% 55.8 54.2% 16.8

Year 5 117 48(48.6; 67.2) (35.7; 87.5) (39.2; 68.6) (9.0; 31.3)

The analysis of immunogenicity was conducted on the ATP cohort.(1) blood sampling performed 21 to 48 days post vaccination

*rSBA analysis performed at PHE laboratories

**hSBA analysis performed at GSK laboratoriesrSBA and hSBA titres were determined over a period of 10 years in children initially vaccinated withone dose of Nimenrix or MenC-CRM at 12 to 23 months of age in Study MenACWY-TT-027.

Persistence of SBA titres was evaluated in two extension studies: MenACWY-TT-032 (up to 5 years)and MenACWY-TT-100 (up to 10 years). Study MenACWY-TT-100 also evaluated the response to asingle booster dose of Nimenrix administered 10 years following the initial vaccination with Nimenrixor MenC-CRM. Results are shown in Table 6 (see section 4.4).

Table 6: rSBA and hSBA titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged12-23 months, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-027/032/100)

Meningo rSBA* hSBA**

Vaccine Time pointcoccal ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)(1) 100% 3707 91.2% 59.0

Month 1 222 217(98.4; 100) (3327; 4129) (86.7; 94.6) (49.3; 70.6)(2) 64.4% 35.1 52.3% 8.8

Year 4 45 44(48.8; 78.1) (19.4; 63.4) (36.7; 67.5) (5.4; 14.2)73.5% 37.4 35.6% 5.2

A Nimenrix Year 5(2) 49 45(58.9; 85.1) (22.1; 63.2) (21.9: 51.2) (3.4; 7.8)

Year 10(3) 66.1% 28.9 25.4% 4.262 59(Pre-booster) (53.0; 77.7) (16.4; 51.0) (15.0; 38.4) (3.0; 5.9)98.4% 5122 100% 1534(Post-booster)(3,4) 62 62(91.3; 100) (3726; 7043) (94.2; 100) (1112; 2117)100% 879 99.1% 190

Month 1(1) 220 221(98.3; 100) (779; 991) (96.8; 99.9) (165; 219)(2) 97.8% 110 97.8% 370

Year 4 45 45(88.2; 99.9) (62.7; 192) (88.2; 99.9) (214; 640)(2) 77.6% 48.9 91.7% 216

Nimenrix Year 5 49 48(63.4; 88.2) (28.5; 84.0) (80.0; 97.7) (124; 379)

Year 10(3) 82.3% 128 91.7% 34962 60(Pre-booster) (70.5; 90.8) (71.1; 231) (81.6; 97.2) (197; 619)100% 7164 100% 33960(Post-booster)(3,4) 62 59(94.2; 100) (5478; 9368) (93.9; 100) (23890; 48274)

C(1) 98.5% 415 72.1% 21.2

Month 1 68 68(92.1; 100) (297; 580) (59.9; 82.3) (13.9; 32.3)(2) 80.0% 137 70.0% 91.9

Year 4 10 10(44.4; 97.5) (22.6; 832) (34.8; 93.3) (9.8; 859)

MenC-(2) 63.6% 26.5 90.9% 109

CRM Year 5 11 11(30.8; 89.1) (6.5; 107) (58.7; 99.8) (21.2; 557)vaccine

Year 10(3) 87.5% 86.7 93.3% 11716 15(Pre-booster) (61.7; 98.4) (29.0; 259) (68.1; 99.8) (40.0; 344)100% 5793 100% 42559(Post-booster)(3,4) 16 15(79.4; 100) (3631; 9242) (78.2; 100) (20106; 90086)100% 5395 79.7% 38.8

W-135 Nimenrix Month 1(1) 222 177(98.4; 100) (4870; 5976) (73.0; 85.3) (29.7; 50.6)

Table 6: rSBA and hSBA titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged12-23 months, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-027/032/100)

Meningo rSBA* hSBA**

Vaccine Time pointcoccal ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)

Year 4(2) 60.0% 50.8 84.4% 76.945 45(44.3; 74.3) (24.0; 108) (70.5; 93.5) (44.0; 134)(2) 34.7% 18.2 82.6% 59.7

Year 5 49 46(21.7; 49.6) (9.3; 35.3) (68.6; 92.2) (35.1; 101)

Year 10(3) 30.6% 15.8 44.2% 7.762 52(Pre-booster) (19.6; 43.7) (9.1; 27.6) (30.5; 58.7) (4.9; 12.2)100% 25911 100% 11925(Post-booster)(3,4) 62 62(94.2; 100) (19120; 35115) (94.2; 100) (8716; 16316)(1) 100% 2824 66.7% 24.4

Month 1 222 201(98.4; 100) (2529; 3153) (59.7; 73.1) (18.6; 32.1)

Year 4(2) 62.2% 44.9 87.8% 74.645 41(46.5; 76.2) (22.6; 89.3) (73.8; 95.9) (44.5; 125)42.9% 20.6 80.0% 70.6

Y Nimenrix Year 5(2) 49 45(28.8; 57.8) (10.9; 39.2) (65.4; 90.4) (38.7; 129)

Year 10(3) 45.2% 27.4 42.9% 9.162 56(Pre-booster) (32.5; 58.3) (14.7; 51.0) (29.7; 56.8) (5.5; 15.1)98.4% 7661 100% 12154(Post-booster)(3,4) 62 61(91.3; 100) (5263; 11150) (94.1; 100) (9661; 15291)

The analysis of immunogenicity was conducted on the ATP cohorts for 1 month and 5 years post vaccinationand the booster ATP cohort. Subjects with a suboptimal response to meningococcal group C (defined as SBAtitre below the pre-defined assay cut-off) were to receive an additional dose of MenC vaccine before Year 6.

These subjects were excluded from the analysis at Years 4 and 5 but included in the analysis at Year 10.

(1) Study MenACWY-TT-027(2) Study MenACWY-TT-032(3) Study MenACWY-TT-100(4) Blood sampling was performed 1 month after a booster dose at Year 10.

*rSBA analysis performed at GSK laboratories for 1 month post primary vaccination samples and at PHElaboratories in UK for subsequent sampling time points.

**hSBA analysis performed at GSK laboratories and at Neomed in Canada for time points in Study MenACWY-

TT-100.

Study MenACWY-TT-102 evaluated the persistence of SBA titres up to 6 years after a booster dose of

Nimenrix or MenC-CRM197 administered in Study MenACWY-TT-048 to children who initiallyreceived the same vaccine at 12 to 23 months of age in Study MenACWY-TT-039. A single boosterdose was administered 4 years after the initial vaccination. Results are shown in Table 7(see section 4.4).

Table 7: rSBA and hSBA titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged12-23 months, persistence at 4 years and response following a booster 4 years after initialvaccination, and persistence up to 6 years following booster vaccination (Studies MenACWY-

TT-039/048/102)

Meningo rSBA* hSBA**

Vaccine

- coccal Time point ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)(1) 99.7% 2205 77.2% 19.0

Month 1 354 338(98.4; 100) (2008; 2422) (72.4; 81.6) (16.4; 22.1)

Year 4(2) 28.9%74.5% 112 4.8(Pre-Nimenrix 212 187 (22.5; 35.9)(68.1; 80.2) (80.3; 156) (3.9; 5.9)

A Nimenrix booster)100% 7173 99.5% 1343(Post-booster)(2,3) 214 202(98.3; 100) (6389; 8054) (97.3; 100) (1119; 1612)5 years after 89.8% 229 53.3% 13.2137 135booster dose (4) (83.4; 94.3) (163; 322) (44.6; 62.0) (9.6; 18.3)

Table 7: rSBA and hSBA titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged12-23 months, persistence at 4 years and response following a booster 4 years after initialvaccination, and persistence up to 6 years following booster vaccination (Studies MenACWY-

TT-039/048/102)

Meningo rSBA* hSBA**

Vaccine

- coccal Time point ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)6 years after 92.5% 297 58.5% 14.4134 130booster dose (4) (86.7; 96.4) (214; 413) (49.5; 67.0) (10.5; 19.7)99.7% 478 98.5% 196

Month 1(1) 354 341(98.4; 100) (437; 522) (96.6; 99.5) (175; 219)

Year 4(2)39.9% 12.1 73.0% 31.2(Pre-Nimenrix 213 200(33.3; 46.8) (9.6; 15.2) (66.3; 79.0) (23.0; 42.2)booster)

Nimenrix 100% 4512 100% 15831(Post-booster)(2,3) 215 209(98.3; 100) (3936; 5172) (98.3; 100) (13626; 18394)5 years after 80.3% 66.0 99.3% 337137 136booster dose (4) (72.6; 86.6) (48.1; 90.5) (96.0; 100) (261; 435)6 years after 71.6% 39.6 97.7% 259booster dose (4) 134 130(63.2; 79.1) (28.6; 54.6) (93.4; 99.5) (195; 345)

C(1) 97.5% 212 81.9% 40.3

Month 1 121 116(92.9; 99.5) (170; 265) (73.7; 88.4) (29.5; 55.1)

Year 4(2)37.2% 14.3 48.4% 11.9(Pre-MenC- 43 31(23.0; 53.3) (7.7; 26.5) (30.2; 66.9) (5.1; 27.6)

MenC- CRM197 booster)

CRM (2,3) 100% 3718 100% 8646(Post-booster) 43 33vaccine (91.8; 100) (2596; 5326) (89.4; 100) (5887; 12699)5 years after 78.3% 47.3 100% 24123 23booster dose (4) (56.3; 92.5) (19.0; 118) (85.2; 100) (139; 420)6 years after 65.2% 33.0 95.7% 16923 23booster dose (4) (42.7; 83.6) (14.7; 74.2) (78.1; 99.9) (94.1; 305)

Month 1(1) 100% 2682 87.5% 48.9354 336(99.0; 100) (2453; 2932) (83.5; 90.8) (41.2; 58.0)

Year 4(2)48.8% 30.2 81.6% 48.3(Pre-Nimenrix 213 158(41.9; 55.7) (21.9; 41.5) (74.7; 87.3) (36.5; 63.9)booster)

W-135 Nimenrix 100% 10950 100% 14411(Post-booster)(2,3) 215 192(98.3; 100) (9531; 12579) (98.1; 100) (12972; 16010)5 years after 88.3% 184 100% 327(4) 137 136booster dose (81.7; 93.2) (130; 261) (97.3; 100) (276; 388)6 years after 85.8% 172 98.5% 314134 133booster dose (4) (78.7; 91.2) (118; 251) (94.7; 99.8) (255; 388)

Month 1(1) 100% 2729 79.3% 30.9354 329(99.0; 100) (2473; 3013) (74.5; 83.6) (25.8; 37.1)

Year 4(2)58.2% 37.3 65.9% 30.2(Pre-Nimenrix 213 123(51.3; 64.9) (27.6; 50.4) (56.8; 74.2) (20.2; 45.0)booster)

Y Nimenrix (2,3) 100% 4585 100% 6776(Post-booster) 215 173(98.3; 100) (4129; 5093) (97.9; 100) (5961; 7701)5 years after 92.7% 265 97.8% 399(4) 137 137booster dose (87.0; 96.4) (191; 368) (93.7; 99.5) (321; 495)6 years after 94.0% 260 97.7% 316134 131booster dose (4) (88.6; 97.4) (189; 359) (93.5; 99.5) (253; 394)

The analysis of immunogenicity was conducted on the ATP cohort for each time point.(1) Study MenACWY-TT-039(2) Study MenACWY-TT-048(3) Blood sampling was performed 1 month after a booster dose at Year 4.(4) Study MenACWY-TT-102

*rSBA analysis performed at GSK laboratories for 1 month post primary vaccination samples and at PHElaboratories in UK for the subsequent sampling time points.

**hSBA analysis performed at GSK laboratories and at Neomed in Canada for time points in Study

MenACWY-TT-102.

In Study MenACWY-TT-081, a single dose of Nimenrix was demonstrated to be non-inferior toanother licensed MenC-CRM vaccine in terms of vaccine response to group C [94.8% (95% CI: 91.4;97.1) and 95.7% (95% CI: 89.2; 98.8), respectively]. The GMT was lower for the Nimenrix group[2795 (95% CI: 2393; 3263)] versus the MenC-CRM vaccine [5292 (95% CI: 3815; 7340)].

In Study MenACWY-TT-038, a single dose of Nimenrix was demonstrated to be non-inferior to thelicensed ACWY-PS vaccine in terms of vaccine response to the four meningococcal groups as shownin Table 8.

Table 8: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in children aged2-10 years (Study MenACWY-TT-038)

Meningo Nimenrix(1) ACWY-PS vaccine(1)

- coccal VR GMT VR GMT

N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)89.1% 6343 64.6% 2283

A 594 192(86.3; 91.5) (5998; 6708) (57.4; 71.3) (2023; 2577)96.1% 4813 89.7% 1317

C 691 234(94.4; 97.4) (4342; 5335) (85.1; 93.3) (1043; 1663)97.4% 11543 82.6% 2158

W-135 691 236(95.9; 98.4) (10873; 12255) (77.2; 87.2) (1815; 2565)92.7% 10825 68.8% 2613

Y 723 240(90.5; 94.5) (10233; 11452) (62.5; 74.6) (2237; 3052)

The analysis of immunogenicity was conducted on the ATP cohort.(1) Blood sampling performed 1 month post vaccination

VR: vaccine response defined as the proportion of subjects with:

- rSBA titres ≥ 32 for initially seronegative subjects (i.e., pre-vaccination rSBA titre <8)

- at least a 4-fold increase in rSBA titres from pre- to post-vaccination for initially seropositivesubjects (i.e., pre-vaccination rSBA titre ≥ 8)

*rSBA analysis performed at GSK laboratories

Persistence of SBA titres was evaluated in children initially vaccinated in Study MenACWY-TT-081as shown in Table 9 (see section 4.4).

Table 9: rSBA and hSBA titres up to 44 months following Nimenrix (or MenC-CRM) inchildren aged 2-10 years at time of vaccination (Study MenACWY-TT-088)

Meningo Time rSBA* hSBA**

Vaccinecoccal point ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (months) (95% CI) (95% CI) (95% CI) (95% CI)86.5% 196 25.6% 4.632 193 90(80.9; 91.0) (144; 267) (16.9; 35.8) (3.3; 6.3)

A Nimenrix85.7% 307 25.8% 4.844 189 89(79.9; 90.4) (224; 423) (17.1; 36.2) (3.4; 6.7)64.6% 34.8 95.6% 75.932 192 90(57.4; 71.3) (26.0; 46.4) (89.0; 98.8) (53.4; 108)

Nimenrix37.0% 14.5 76.8% 36.444 189 82(30.1; 44.3) (10.9; 19.2) (66.2; 85.4) (23.1; 57.2)

C76.8% 86.5 90.9% 82.2

MenC- 32 69 33(65.1; 86.1) (47.3; 158) (75.7; 98.1) (34.6; 196)

CRM45.5% 31.0 64.5% 38.8vaccine 44 66 31(33.1; 58.2) (16.6; 58.0) (45.4; 80.8) (13.3; 113)

W-135 Nimenrix 32 193 77.2% 214 86 84.9% 69.9(70.6; 82.9) (149; 307) (75.5; 91.7) (48.2; 101)68.3% 103 80.5% 64.344 189 87(61.1; 74.8) (72.5; 148) (70.6; 88.2) (42.7; 96.8)81.3% 227 81.3% 79.232 193 91(75.1; 86.6) (165; 314) (71.8; 88.7) (52.5; 119)

Y Nimenrix62.4% 78.9 82.9% 12744 189 76(55.1; 69.4) (54.6; 114) (72.5; 90.6) (78.0; 206)

The analysis of immunogenicity was conducted on the ATP cohort for persistence adapted for each time point.

*rSBA analysis performed at PHE laboratories in UK

**hSBA analysis performed at GSK laboratories

Persistence of hSBA titres was evaluated 1 year after vaccination in children aged 6-10 years whowere initially vaccinated in Study MenACWY-TT-027 (Table 10) (see section 4.4).

Table 10: hSBA* titres following a single dose of Nimenrix (or ACWY-PS) in children aged6-10 years and persistence 1 year following vaccination (Studies MenACWY-TT-027/028)1 month post-vaccination 1 year persistence

Mening

Vaccine (Study MenACWY-TT-027) (Study MenACWY-TT-028)ococcalgroup ≥ 8 GMT ≥ 8 GMTgroup N N(95% CI) (95% CI) (95% CI) (95% CI)80.0 % 53.4 16.3% 3.5

Nimenrix 105 104(71.1; 87.2) (37.3; 76.2) (9.8; 24.9) (2.7; 4.4)

A

ACWY-PS 25.7% 4.1 5.7% 2.535 35vaccine (12.5; 43.3) (2.6; 6.5) (0.7; 19.2) (1.9; 3.3)89.1% 156 95.2% 129

Nimenrix 101 105(81.3; 94.4) (99.3; 244) (89.2; 98.4) (95.4; 176)

C

ACWY-PS 39.5% 13.1 32.3% 7.738 31vaccine (24.0; 56.6) (5.4; 32.0) (16.7; 51.4) (3.5; 17.3)95.1% 133 100% 257

Nimenrix 103 103(89.0; 98.4) (99.9; 178) (96.5; 100) (218; 302)

W-135

ACWY-PS 34.3% 5.8 12.9% 3.435 31vaccine (19.1; 52.2) (3.3; 9.9) (3.6; 29.8) (2.0; 5.8)83.1% 95.1 99.1% 265

Nimenrix 89 106(73.7;90.2) (62.4; 145) (94.9; 100) (213; 330)

Y

ACWY-PS 43.8% 12.5 33.3% 9.332 36vaccine (26.4; 62.3) (5.6; 27.7) (18.6; 51.0) (4.3; 19.9)

The analysis of immunogenicity was conducted on the ATP cohort for persistence at Year 1.hSBA analysis was not performed for children aged 2 to <6 years (at time of vaccination).

*hSBA analysis performed at GSK laboratories

SBA titres were determined over a period of 10 years in children initially vaccinated with one dose of

Nimenrix or ACWY-PS at 2 to 10 years of age in Study MenACWY-TT-027. Persistence of SBAtitres was evaluated in two extension studies: MenACWY-TT-032 (up to 5 years) and MenACWY-

TT-100 (up to 10 years). Study MenACWY-TT-100 also evaluated the response to a single boosterdose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or ACWY-

PS. Results are shown in Table 11 (see section 4.4).

Table 11: rSBA and hSBA titres following a single dose of Nimenrix (or ACWY-PS) in children aged2-10 years, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-027/032/100)

Meningo- rSBA* hSBA**

Vaccinecoccal Time point ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)100% 7301 81.1% 57.0

A Nimenrix Month 1(1) 225 111(5)(98.4; 100) (6586; 8093) (72.5; 87.9) (40.3; 80.6)

Table 11: rSBA and hSBA titres following a single dose of Nimenrix (or ACWY-PS) in children aged2-10 years, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-027/032/100)

Meningo- rSBA* hSBA**

Vaccinecoccal Time point ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)90.8% 141

Year 5(2) 98 n/a(6) -- --(83.3; 95.7) (98.2; 203)(3) 79.6% 107 41.1% 6.5

Year 6 98 90(70.3; 87.1) (66.0; 174) (30.8; 52.0) (4.8; 8.8)

Year 10(3) 89.0% 96.3 33.9% 4.573 62(Pre-booster) (79.5; 95.1) (57.1; 163) (22.3; 47.0) (3.3; 6.2)95.9% 4626 100% 1213(Post-booster)(3,4) 74 73(88.6; 99.2) (3041; 7039) (95.1; 100) (994; 1481)100% 2033 25.7% 4.1

Month 1(1) 75 35(5)(95.2; 100) (1667; 2480) (12.5; 43.3) (2.6; 6.5)(2) 15.4% 4.7

Year 5 13 n/a(6) -- --(1.9; 45.4) (3.7; 6.0)

ACWY-12.5% 5.8 33.3% 5.9

PS Year 6(3) 24 21(2.7; 32.4) (3.5; 9.6) (14.6; 57.0) (3.0; 11.7)vaccine

Year 10(3) 23.5% 8.0 29.4% 6.217 17(Pre-booster) (6.8; 49.9) (3.3; 19.3) (10.3; 56.0) (2.4; 15.7)(3,4) 100% 6414 100% 211(Post-booster) 17 17(80.5; 100) (3879; 10608) (80.5; 100) (131; 340)(1) 100% 2435 89.7% 155

Month 1 225 107(5)(98.4; 100) (2106; 2816) (82.3; 94.8) (101; 237)90.8% 79.7

Year 5(2) 98 n/a(6) -- --(83.3; 95.7) (56.0; 113)(3) 82.7% 193 93.8% 427

Nimenrix Year 6 98 97(73.7; 89.6) (121; 308) (87.0; 97.7) (261; 700)

Year 10(3) 85.1% 181 91.8% 22274 73(Pre-booster) (75.0; 92.3) (106; 310) (83.0; 96.9) (129; 380)(Post-booster)(3,4) 100% 4020 100% 1554474 71(95.1; 100) (3319; 4869) (94.9; 100) (11735; 20588)

C100% 750 39.5% 13.1

Month 1(1) 74 38(5)(95.1; 100) (555; 1014) (24.0; 56.6) (5.4; 32.0)100% 128

Year 5(2) 13 n/a(6) -- --(75.3; 100) (56.4; 291)

ACWY-79.2% 98.7 100% 235

PS Year 6(3) 24 24(57.8; 92.9) (42.2; 231) (85.8; 100) (122; 451)vaccine

Year 10(3) 76.5% 96.2 100% 99.117 17(Pre-booster) (50.1; 93.2) (28.9; 320) (80.5; 100) (35.8; 274)(3,4) 100% 15101 94.1 44794(Post-booster) 17 17(80.5; 100) (7099; 32122) (71.3; 99.9) (10112; 198440)100% 11777 95.3% 134

Month 1(1) 225 107(5)(98.4; 100) (10666; 13004) (89.4; 98.5) (101; 178)78.6% 209

Year 5(2) 98 n/a(6) -- --(69.1; 86.2) (128; 340)(3) 73.5% 265 81.5% 62.5

Nimenrix Year 6 98 92(63.6; 81.9) (155; 454) (72.1; 88.9) (42.0; 93.1)

Year 10(3) 68.9% 206 61.0% 17.574 59(Pre-booster) (57.1; 79.2) (109; 392) (47.4; 73.5) (10.5; 29.2)

W-135100% 27944 100% 6965(Post-booster)(3,4) 74 74(95.1; 100) (22214; 35153) (95.1; 100) (5274; 9198)(1) 100% 2186 34.3% 5.8

Month 1 75 35(5)(95.2; 100) (1723; 2774) (19.1; 52.2) (3.3, 9.9)

ACWY-0% 4.0

PS Year 5(2) 13 n/a(6) -- --(0.0; 24.7) (4.0; 4.0)vaccine12.5% 7.6 30.4% 7.0

Year 6(3) 24 23(2.7; 32.4) (3.7; 15.6) (13.2; 52.9) (2.9; 16.9)

Table 11: rSBA and hSBA titres following a single dose of Nimenrix (or ACWY-PS) in children aged2-10 years, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-027/032/100)

Meningo- rSBA* hSBA**

Vaccinecoccal Time point ≥ 8 GMT ≥ 8 GMTgroup N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)

Year 10(3) 23.5% 15.4 26.7% 4.117 15(Pre-booster) (6.8; 49.9) (4.2; 56.4) (7.8; 55.1) (2.0; 8.5)(3,4) 94.1% 10463 100% 200(Post-booster) 17 15(71.3; 99.9) (3254; 33646) (78.2; 100) (101; 395)100% 6641 83.0% 93.7

Month 1(1) 225 94(5)(98.4; 100) (6044; 7297) (73.8; 89.9) (62.1; 141)78.6% 143

Year 5(2) 98 n/a(6) -- --(69.1; 86.2) (88.0; 233)71.4% 136 65.2% 40.3

Nimenrix Year 6(3) 98 89(61.4; 80.1) (82.6; 225) (54.3; 75.0) (23.9; 68.1)

Year 10(3) 67.6% 98.5 72.3% 35.774 65(Pre-booster) (55.7; 78.0) (54.3; 179) (59.8; 82.7) (21.0; 60.6)100% 7530 100% 11127(Post-booster)(3,4) 74 74(95.1; 100) (5828; 9729) (95.1; 100) (8909; 13898)

Y(1) 100% 1410 (5) 43.8% 12.5

Month 1 75 32(95.2; 100) (1086; 1831) (26.4; 62.3) (5.6; 27.7)7.7% 5.5

Year 5(2) 13 n/a(6) -- --(0.2; 36.0) (2.7; 11.1)

ACWY-20.8% 11.6 25.0% 7.3

PS Year 6(3) 24 24(7.1; 42.2) (4.7; 28.7) (9.8; 46.7) (2.7; 19.8)vaccine

Year 10(3) 17.6% 10.2 35.7% 7.817 14(Pre-booster) (3.8; 43.4) (3.5; 30.2) (12.8; 64.9) (2.5; 24.4)(Post-booster)(3,4) 100% 6959 100% 45417 17(80.5; 100) (3637; 13317) (80.5; 100) (215; 960)

The analysis of immunogenicity was conducted on the ATP cohort for each time point. Subjects with asuboptimal response to meningococcal group C (defined as SBA titre below the pre-defined assay cut-off) wereto receive an additional dose of MenC vaccine before Year 6. These subjects were excluded from the analysis at

Year 5 but included in the analyses at Years 6 and 10.

(1) Study MenACWY-TT-027(2) Study MenACWY-TT-032(3) Study MenACWY-TT-100(4) Blood sampling was performed 1 month after a booster dose at Year 10.(5) Includes children aged 6 to <11 years. hSBA analysis was not performed for children aged 2 to <6 years(at time of vaccination).(6) Per the protocol for Study MenACWY-TT-032, hSBA was not measured for this age group at Year 5.

*rSBA analysis performed at GSK laboratories for 1 month post primary vaccination samples and at PHElaboratories in UK for subsequent sampling time points.

**hSBA analysis performed at GSK laboratories and at Neomed in Canada for time points in Study

MenACWY-TT-100.

In two clinical studies, conducted in adolescents aged 11-17 years (Study MenACWY-TT-036) and inadults aged 18-55 years (Study MenACWY-TT-035), either one dose of Nimenrix or one dose of the

ACWY-PS vaccine was administered.

Nimenrix was demonstrated to be immunologically non-inferior to the ACWY-PS vaccine in terms ofvaccine response as shown in Table 12.

Table 12: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in adolescentsaged 11-17 years and adults aged 18-55 years (Studies MenACWY-TT-035/036)

Study MenACWY-TT-036 Study MenACWY-TT-035

Meningo-

Vaccine (11-17 years)(1) (18-55 years)(1)coccalgroup VR GMT VR GMTgroup N N(95% CI) (95% CI) (95% CI) (95% CI)

Nimenrix 85.4% 5928 80.1% 3625553 743(82.1; 88.2) (5557; 6324) (77.0; 82.9) (3372; 3897)

A

ACWY-PS 77.5% 2947 69.8% 2127191 252vaccine (70.9; 83.2) (2612; 3326) (63.8; 75.4) (1909; 2370)

Nimenrix 97.4% 13110 91.5% 8866642 849(95.8; 98.5) (11939; 14395) (89.4; 93.3) (8011; 9812)

C

ACWY-PS 96.7% 8222 92.0% 7371211 288vaccine (93.3; 98.7) (6807; 9930) (88.3; 94.9) (6297; 8628)

Nimenrix 96.4% 8247 90.2% 5136639 860(94.6; 97.7) (7639; 8903) (88.1; 92.1) (4699; 5614)

W-135

ACWY-PS 87.5% 2633 85.5% 2461216 283vaccine (82.3; 91.6) (2299; 3014) (80.9; 89.4) (2081; 2911)

Nimenrix 93.8% 14086 87.0% 7711657 862(91.6; 95.5) (13168; 15069) (84.6; 89.2) (7100; 8374)

Y

ACWY-PS 78.5% 5066 78.8% 4314219 288vaccine (72.5; 83.8) (4463; 5751) (73.6; 83.4) (3782; 4921)

The analysis of immunogenicity was conducted on the ATP cohorts.(1) Blood sampling performed 1 month post vaccination

VR: vaccine response defined as the proportion of subjects with:

- rSBA titres ≥ 32 for initially seronegative subjects (i.e., pre-vaccination rSBA titre <8)

- at least a 4-fold increase in rSBA titres from pre- to post-vaccination for initially seropositive subjects (i.e.,pre-vaccination rSBA titre ≥ 8)

*rSBA analysis performed at GSK laboratoriesrSBA titres were determined over a period of 10 years in subjects initially vaccinated with one dose of

Nimenrix or ACWY-PS at 11 to 17 years of age in Study MenACWY-TT-036. Persistence of rSBAtitres was evaluated in two extension studies: MenACWY-TT-043 (up to 5 years) and MenACWY-

TT-101 (at 10 years). Study MenACWY-TT-101 also evaluated the response to a single booster doseof Nimenrix administered 10 years following the initial vaccination with Nimenrix or ACWY-PS.

Results are shown in Table 13.

Table 13: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in adolescents aged11-17 years, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-036/043/101)

Meningo- Nimenrix ACWY-PS vaccine

Time pointcoccal ≥ 8 GMT ≥ 8 GMT

N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)

Month 1(1) 100% 5929 99.6% 2947674 224(99.5; 100) (5557; 6324) (97.5; 100) (2612; 3326)(2) 92.9% 448 82.7% 206

Year 3 449 150(90.1; 95.1) (381; 527) (75.6; 88.4) (147; 288)

A Year 5(2) 97.5% 644 93.0% 296236 86(94.5; 99.1) (531; 781) (85.4; 97.4) (202; 433)

Year 10(3) 85.2% 248 80.4% 143162 51(Pre-booster) (78.8; 90.3) (181; 340) (66.9; 90.2) (80.5; 253)100% 3760 100% 2956(Post-booster)(3,4) 162 51(97.7; 100) (3268; 4326) (93.0; 100) (2041; 4282)

Table 13: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in adolescents aged11-17 years, persistence up to 10 years, and post-booster administered 10 years followinginitial vaccination (Studies MenACWY-TT-036/043/101)

Meningo- Nimenrix ACWY-PS vaccine

Time pointcoccal ≥ 8 GMT ≥ 8 GMT

N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)(1) 100% 13110 100% 8222

Month 1 673 224(99.5; 100) (11939; 14395) (98.4; 100) (6808; 9930)91.1% 371 86.0% 390

Year 3(2) 449 150(88.1; 93.6) (309; 446) (79.4; 91.1) (262; 580)(2) 88.6% 249 87.1% 366

C Year 5 236 85(83.8; 92.3) (194; 318) (78.0; 93.4) (224; 599)

Year 10(3) 90.1% 244 82.4% 177162 51(Pre-booster) (84.5; 94.2) (182; 329) (69.1; 91.6) (86.1; 365)(Post-booster)(3,4) 100% 8698 100% 3879162 51(97.7; 100) (7391 10235) (93.0; 100) (2715; 5544)

Month 1(1) 99.9% 8247 100% 2633678 224(99.2; 100) (7639; 8903) (98.4; 100) (2299; 3014)82.0% 338 30.0% 16.0

Year 3(2) 449 150(78.1; 85.4) (268; 426) (22.8; 38.0) (10.9; 23.6)86.0% 437 34.9% 19.7

W-135 Year 5(2) 236 86(80.9; 90.2) (324; 588) (24.9; 45.9) (11.8; 32.9)

Year 10(3) 71.6% 146 43.1% 16.4162 51(Pre-booster) (64.0; 78.4) (97.6; 217) (29.3; 57.8) (9.2; 29.4)(Post-booster)(3,4) 100% 11243 100% 3674162 51(97.7; 100) (9367; 13496) (93.0; 100) (2354; 5734)(1) 100% 14087 100% 5066

Month 1 677 224(99.5; 100) (13168; 15069) (98.4; 100) (4463; 5751)

Year 3(2) 93.1% 740 58.0% 69.6449 150(90.3; 95.3) (620; 884) (49.7; 66.0) (44.6; 109)(2) 96.6% 1000 66.3% 125

Y Year 5 236 86(93.4; 98.5) (824; 1214) (55.3; 76.1) (71.2; 219)

Year 10(3) 90.7% 447 49.0% 32.9162 51(Pre-booster) (85.2; 94.7) (333; 599) (34.8; 63.4) (17.1; 63.3)(Post-booster)(3,4) 100% 7585 98.0% 3296162 51(97.7; 100) (6748; 8525) (89.6; 100) (1999; 5434)

The analysis of immunogenicity was conducted on the ATP cohort for each time point.

(1) Study MenACWY-TT-036(2) Study MenACWY-TT-043(3) Study MenACWY-TT-101(4) Blood sampling was performed 1 month after a booster dose at Year 10.

*rSBA analysis performed at GSK laboratories for 1 month post primary vaccination samples and at PHElaboratories in UK for the subsequent sampling time points.

hSBA persistence was evaluated up to 5 years after vaccination in adolescents and adults initiallyvaccinated in Study MenACWY-TT-052 as shown in Table 14 (see section 4.4).

Table 14: hSBA* titres following a single dose of Nimenrix in adolescents and adults aged11-25 years and persistence up to 5 years following vaccination (Studies MenACWY-

TT-052/059)

Meningococcal Time

N ≥ 8 (95% CI) GMT (95% CI)group point

Month 1(1) 356 82.0% (77.6; 85.9) 58.7 (48.6; 70.9)

A Year 1(2) 350 29.1% (24.4; 34.2) 5.4 (4.5; 6.4)

Year 5(2) 141 48.9% (40.4; 57.5) 8.9 (6.8; 11.8)

Month 1(1) 359 96.1% (93.5; 97.9) 532 (424; 668)

C Year 1(2) 336 94.9% (92.0; 97.0) 172 (142; 207)

Year 5(2) 140 92.9% (87.3; 96.5) 94.6 (65.9; 136)

Month 1(1) 334 91.0% (87.4; 93.9) 117 (96.8; 141)

W-135 Year 1(2) 327 98.5% (96.5; 99.5) 197 (173; 225)

Year 5(2) 138 87.0% (80.2; 92.1) 103 (76.3; 140)

Month 1(1) 364 95.1% (92.3; 97.0) 246 (208; 291)

Y Year 1(2) 356 97.8% (95.6; 99.0) 272 (237; 311)

Year 5(2) 142 94.4% (89.2; 97.5) 225 (174; 290)

The analysis of immunogenicity was conducted on the ATP cohort for persistence adapted for each time point.(1) Study MenACWY-TT-052(2) Study MenACWY-TT-059

*hSBA analysis performed at GSK laboratoriesrSBA titres were determined over a period of 10 years in subjects initially vaccinated with one dose of

Nimenrix or ACWY-PS at 11 to 55 years of age in Study MenACWY-TT-015. Persistence of rSBAtitres was evaluated in two extension studies: MenACWY-TT-020 (up to 5 years) and MenACWY-

TT-099 (up to 10 years). Study MenACWY-TT-099 also evaluated the response to a single boosterdose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or ACWY-

PS. Results are shown in Table 15.

Table 15: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in adolescents andadults aged 11-55 years, persistence up to 10 years, and post-booster administered10 years following initial vaccination (Studies MenACWY-TT-015/020/099)

Meningo- Nimenrix ACWY-PS vaccinecoccal Time point ≥ 8 GMT ≥ 8 GMT

N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)100% 4945 100% 2190

Month 1(1) 323 112(98.9; 100) (4452, 5493) (96.8, 100) (1858, 2582)95.3% 365 76.5% 104

Year 4(2) 43 17(84.2; 99.4) (226; 590) (50.1; 93.2) (31.0; 351)84.3% 190 57.9% 37.0

A Year 5(2) 51 19(71.4; 93.0) (108; 335) (33.5; 79.7) (12.6; 109)

Year 10(3) 78.1% 154 71.2% 75.1155 52(Pre-booster) (70.7; 84.3) (108; 219) (56.9; 82.9) (41.4; 136)(3,4) 100% 4060 100% 3585(Post-booster) 155 52(97.6; 100) (3384; 4870) (93.2; 100) (2751; 4672)99.7% 10074 100% 6546

Month 1(1) 341 114(98.4; 100) (8700, 11665) (96.8; 100) (5048; 8488)(2) 76.7% 126 41.2% 16.7

Year 4 43 17(61.4; 88.2) (61.6; 258) (18.4; 67.1) (5.7; 48.7)(2) 72.5% 78.5 38.9% 17.3

C Year 5 51 18(58.3; 84.1) (41.8; 147) (17.3; 64.3) (6.0; 49.7)

Year 10(3) 90.9% 193 88.5% 212154 52(Pre-booster) (85.2; 94.9) (141; 264) (76.6; 95.6) (110; 412)(Post-booster)(3,4) 100% 13824 98.1% 3444155 52(97.6; 100) (10840; 17629) (89.7; 100) (1999; 5936)

Table 15: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in adolescents andadults aged 11-55 years, persistence up to 10 years, and post-booster administered10 years following initial vaccination (Studies MenACWY-TT-015/020/099)

Meningo- Nimenrix ACWY-PS vaccinecoccal Time point ≥ 8 GMT ≥ 8 GMT

N Ngroup (95% CI) (95% CI) (95% CI) (95% CI)

Month 1(1) 99.7% 8577 100% 2970340 114(98.4; 100) (7615; 9660) (96.8; 100) (2439; 3615)90.7% 240 17.6% 8.3

Year 4(2) 43 17(77.9; 97.4) (128; 450) (3.8; 43.4) (3.6; 19.5)86.3% 282 31.6% 15.4

W-135 Year 5(2) 51 19(73.7; 94.3) (146; 543) (12.6; 56.6) (5.7; 41.9)

Year 10(3) 71.4% 166 21.2% 10.9154 52(Pre-booster) (63.6; 78.4) (107; 258) (11.1; 34.7) (6.1; 19.3)100% 23431 98.1% 5793(Post-booster)(3,4) 155 52(97.6; 100) (17351; 31641) (89.7; 100) (3586; 9357)100% 10315 100% 4574

Month 1(1) 340 114(98.9; 100) (9317; 11420) (96.8; 100) (3864; 5414)(2) 86.0% 443 47.1% 30.7

Year 4 43 17(72.1; 94.7) (230; 853) (23.0; 72.2) (9.0; 105)(2) 92.2% 770 63.2% 74.1

Y Year 5 51 19(81.1; 97.8) (439; 1351) (38.4; 83.7) (21.9; 250)

Year 10(3) 86.4% 364 61.5% 56.0154 52(Pre-booster) (79.9; 91.4) (255; 519) (47.0; 74.7) (28.8; 109)100% 8958 100% 5138(Post-booster)(3,4) 155 52(97.6; 100) (7602; 10558) (93.2; 100) (3528; 7482)

The analysis of immunogenicity was conducted on the ATP cohorts for 1 month and 5 years post vaccinationand the booster ATP cohort.

(1) Study MenACWY-TT-015(2) Study MenACWY-TT-020(3) Study MenACWY-TT-099(4) Blood sampling was performed 1 month after a booster dose at Year 10.

*rSBA analysis performed at GSK laboratories for 1 month post primary vaccination samples and at PHElaboratories in UK for the subsequent sampling time points.

In a separate study (MenACWY-TT-085), a single dose of Nimenrix was administered to 194

Lebanese adults aged 56 years and older (including 133 aged 56-65 years and 61 aged >65 years). Thepercentage of subjects with rSBA titres (measured at GSK’s laboratories) ≥ 128 before vaccinationranged from 45% (group C) to 62% (group Y). Overall, at 1 month post-vaccination the percentage ofvaccines with rSBA titres ≥ 128 ranged from 93% (group C) to 97% (group Y). In the subgroup aged>65 years the percentage of vaccines with rSBA titres ≥ 128 at 1 month post-vaccination ranged from90% (group A) to 97% (group Y).

Booster response for subjects previously vaccinated with a conjugate meningococcal vaccine against

Neisseria meningitidis

Nimenrix booster vaccination in subjects previously primed with a monovalent (MenC-CRM) or aquadrivalent conjugate meningococcal vaccine (MenACWY-TT) was studied in subjects from12 months of age onwards who received a booster vaccination. Robust anamnestic responses to theantigen(s) in the priming vaccine were observed (see Tables 6, 7, 11, 13, and 15).

Response to Nimenrix in subjects previously vaccinated with a plain polysaccharide vaccine against

Neisseria meningitidis

In Study MenACWY-TT-021 conducted in subjects aged 4.5-34 years, the immunogenicity of

Nimenrix administered between 30 and 42 months after vaccination with a ACWY-PS vaccine wascompared to the immunogenicity of Nimenrix administered to age-matched subjects who had not beenvaccinated with any meningococcal vaccine in the preceding 10 years. An immune response (rSBAtitre ≥ 8) was observed against all four meningococcal groups in all subjects regardless of themeningococcal vaccine history. The rSBA GMTs were significantly lower in the subjects who hadreceived a dose of ACWY-PS vaccine 30-42 months prior to Nimenrix, however 100% of subjectsachieved rSBA titres ≥ 8 for all four meningococcal groups (A, C, W-135, Y) (see section 4.4).

Study MenACWY-TT-084 compared immune responses to two doses of Nimenrix given 2 monthsapart between 43 subjects aged 2-17 years with anatomic or functional asplenia subjects and43 age-matched subjects with normal splenic function. One month after the first vaccine dose and1 month after the second dose similar percentages of subjects in the two groups had rSBA titres ≥ 8and ≥ 128 and hSBA titres ≥ 4 and ≥ 8.

Immunogenicity following two doses of Nimenrix at 3 and 12 months of age

In study C0921062, infants received a single primary dose at 3 months of age followed by a boosterdose at 12 months of age. A single primary dose administered at 3 months of age elicited robust rSBAtitres to the four meningococcal groups, as measured by the percentage of subjects with rSBA titres ≥8 and GMTs. A booster dose produced robust responses against all four meningococcal groups.

Results are shown in Table 16.

Table 16: rSBA titres pre- and post-vaccination with two doses at 3 and 12 months of age (Study

C0921062)rSBA*

Meningococcal

Time pointgroup ≥ 8 GMT

N(95% CI) (95% CI)0.0% 4.0

Pre-dose 1 128(0.0; 2.8) (4.0; 4.0)(1) 82.3% 54.7

Post-dose 1 124(74.4; 88.5) (41.1; 72.9)

A33.6% 9.9

Pre-booster 125(25.4; 42.6) (7.6; 13.0)100% 1818

Post-booster(1) 128(97.2; 100) (1498; 2207)4.7% 4.4

Pre-dose 1 128(1.7; 9.9) (4.0; 4.7)91.1% 108

Post-dose 1(1) 124(84.7; 95.5) (81.3; 143)

C64.8% 21.8

Pre-booster 125(55.8; 73.1) (16.1; 29.5)(1) 100% 1300

Post-booster 128(97.2; 100) (1052; 1605)0.8% 4.1

Pre-dose 1 128(0.0; 4.3) (3.9; 4.3)89.5% 202

Post-dose 1(1) 124(82.7; 94.3) (150; 274)

W67.2% 21.7

Pre-booster 125(58.2; 75.3) (16.3; 28.9)100% 2714

Post-booster (1) 128(97.2; 100) (2233; 3299)7.8% 5.0

Pre-dose 1 128(3.8; 13.9) (4.3; 5.8)

Post-dose 1(1) 90.3% 187(83.7; 94.9) (142; 248)

Y66.4% 24.5

Pre-booster 125(57.4; 74.6) (18.0; 33.4)

Post-booster (1) 100% 1667(97.2; 100) (1394; 1994)

*rSBA analysis performed at UK Health Security Agency (UKHSA) laboratories(1) blood sampling performed 1 month post vaccinationhSBA secondary endpoint data are not included in the table due to limited data.

In 2018, the Netherlands added Nimenrix to the national immunisation programme as a single dose fortoddlers at 14 months of age to replace the meningococcal C conjugate vaccine. A catch-up campaignwith a single dose of Nimenrix for adolescents 14-18 years of age also initiated in 2018, and it becameroutine in 2020 leading to a toddler and adolescent national immunisation programme. Within twoyears, the incidence of meningococcal disease caused by groups C, W, and Y was significantlyreduced by 100% (95% CI: 14, 100) in individuals 14-18 years of age, 85% (95% CI: 32, 97) in allvaccine eligible ages (direct effect), and 50% (95% CI: 28, 65) in non-vaccine eligible ages (indirecteffect). The impact of Nimenrix was primarily driven by a reduction in group W disease.

Not applicable.

Non-clinical data reveal no special hazard for humans based on local tolerance, acute toxicity,repeated dose toxicity, developmental/reproductive toxicity and fertility studies.

Sucrose

Trometamol

Sodium chloride

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.

4 years

The unopened vial is stable for 72 hours when stored at temperatures from 0 °C to 2 °C or from 8 °Cto 25 °C. At the end of this period, Nimenrix should be used or discarded. These data are intended toguide healthcare professionals in case of temporary temperature excursions only.

After reconstitution, the vaccine should be used promptly. Although delay is not recommended,stability has been demonstrated for 8 hours at 30 °C after reconstitution. If not used within 8 hours, donot administer the vaccine.

Store in a refrigerator (2 °C - 8 °C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Powder in a vial (type I glass) with a stopper (butyl rubber) and solvent in a pre-filled syringe with astopper (butyl rubber).

Pack sizes of 1 and 10 with or without needles.

Not all pack sizes may be marketed.

Instructions for reconstitution of the vaccine with the solvent presented in pre-filled syringe

Nimenrix must be reconstituted by adding the entire content of the pre-filled syringe of solvent to thevial containing the powder.

To attach the needle to the syringe, refer to the below picture. However, the syringe provided with

Nimenrix might be slightly different (without screw thread) than the syringe described in the picture.

In that case, the needle should be attached without screwing.

1. Holding the syringe barrel in one hand(avoid holding the syringe plunger),unscrew the syringe cap by twisting it anticlockwise.

Syringe plunger

Syringe barrel

Syringe cap2. To attach the needle to the syringe,twist the needle clockwise into the syringeuntil you feel it lock (See picture).

3. Remove the needle protector, which onoccasion can be a little stiff.

4. Add the solvent to the powder. After the addition Needle protectorof the solvent to the powder, the mixture shouldbe well shaken until the powder is completelydissolved in the solvent.

The reconstituted vaccine is a clear colourlesssolution.

The reconstituted vaccine should be inspected visually for any foreign particulate matter and/orvariation of physical aspect prior to administration. In the event of either being observed, discard thevaccine.

After reconstitution, the vaccine should be used promptly.

A new needle should be used to administer the vaccine.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Pfizer Europe MA EEIG

Boulevard de la Plaine 171050 Bruxelles

Belgium

EU/1/12/767/001

EU/1/12/767/002

EU/1/12/767/003

EU/1/12/767/004

Date of first authorisation: 20 April 2012

Date of latest renewal: 16 February 2017

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.