Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: vaccines, meningococcal vaccines, ATC code: J07AH08 
Mechanism of action

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

Immunogenicity in infants

In Study MenACWY-TT-083, the first dose was administered at 6 to 12 weeks of age, the second after an 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 elicited rSBA and hSBA titres against the four meningococcal groups as shown in Table 2. The response against group C was non-inferior to the one elicited by licensed MenC-CRM and MenC-TT vaccines in 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 infants from 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 and following a booster at 12 months of age (Study MenACWY-TT-083) rSBA*                                 hSBA**
Meningo-
Vaccine     Time coccal group      point                  ≥8              GMT                    ≥8           GMT group                               N                                        N (95% CI)       (95% CI)             (95% CI)        (95% CI)
Post-                 97.4%            203                96.5%            157 456                                    202 dose 2(1)            (95.4; 98.6)    (182; 227)          (93.0; 98.6)    (131; 188) A      Nimenrix
Post-                 99.6%           1561                99.5%           1007 462                                    214 booster(1)           (98.4; 99.9)  (1412; 1725)           (97.4;100)     (836;1214) Post-                 98.7%            612                98.6%           1308 456                                    218 dose 2(1)            (97.2; 99.5)    (540; 693)          (96.0; 99.7)   (1052; 1627) Nimenrix
Post-                 99.8%           1177                99.5%           4992 463                                    221 booster(1)           (98.8; 100)   (1059; 1308)          (97.5; 100)    (4086; 6100) Post-                 99.6%            958                100%            3188 MenC-                  455                                    202 dose 2(1)            (98.4; 99.9)   (850; 1079)          (98.2; 100)    (2646; 3841) C         CRM
Post-                 98.4%           1051                100%            5438 vaccine                 446                                    216 booster(1)           (96.8; 99.4)   (920; 1202)          (98.3; 100)    (4412; 6702) Post-                 100%            1188                100%            2626 MenC-                  457                                    226 dose 2(1)            (99.2; 100)   (1080; 1307)          (98.4; 100)    (2219; 3109) TT
Post-                 100%            1960                100%            5542 vaccine                 459                                    219 booster(1)           (99.2; 100)   (1776; 2163)          (98.3; 100)    (4765; 6446) Post-                 99.1%           1605                100%             753 455                                    217 dose 2(1)            (97.8; 99.8)  (1383; 1862)          (98.3; 100)     (644; 882) W      Nimenrix
Post-                 99.8%           2777                100%            5123 462                                    218 booster(1)           (98.8; 100)   (2485; 3104)          (98.3; 100)    (4504; 5826) Post-                 98.2%            483                97.7%            328 456                                    214 dose 2(1)            (96.6; 99.2)    (419; 558)          (94.6; 99.2)    (276; 390) Y      Nimenrix
Post-                 99.4%            881                100%            2954 462                                    217 booster(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 a booster dose at 15-18 months (DTaP-IPV/Hib and 10-valent pneumococcal conjugate vaccine was co-administered at both vaccination time points) or three primary doses at 2, 4, and 6 months followed by a booster dose at 15-18 months. A single primary dose administered at 6 months of age elicited robust rSBA titres to the four meningococcal groups, as measured by the percentage of subjects with rSBA titres ≥8, that were comparable to responses after the last dose of a three-dose primary series. A booster dose produced robust responses, comparable between the two dosing groups, against all four meningococcal 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 age and pre-and post-booster at 15-18 months of age (Study MenACWY-TT-087) 
Meningo-                                     rSBA*                                hSBA** Time coccal point                ≥8                  GMT                 ≥8                GMT group                    N                                         N
(95% CI)             (95% CI)           (95% CI)           (95% CI)

Post-dose            98.8%                  1333              98.3%               271 163                                       59
1(1)            (95.6; 99.9)         (1035; 1716)        (90.9; 100)        (206; 355) 
Pre-                81.7%                 125               66.2%                20.8 A                     131                                       71 booster            (74; 87.9)          (84.4; 186)          (54; 77)          (13.5; 32.2) 
Post-              99.3%                  2762              100%                1416 139                                       83 booster(1)         (96.1; 100)          (2310; 3303)        (95.7; 100)       (1140; 1758) 
Post-dose            99.4%                  592               100%                523 163                                       66
1(1)            (96.6; 100)           (482; 726)         (94.6;100)         (382; 717) Pre-               65.6%                 27.4               96.2%               151 C                     131                                       78 booster           (56.9; 73.7)         (20.6; 36.6)        (89.2; 99.2)       (109; 210) Post-              99.3%                  2525              100%             13360 139                                       92 booster(1)         (96.1; 100)          (2102; 3033)        (96.1; 100)    (10953; 16296) 
Post-dose             93.9%                1256               87.2%               137 163                                       47
1(1)              (89; 97)           (917; 1720)         (74.3; 95.2)       (78.4; 238) 
W          Pre-               77.9%                 63.3               100%                429 131                                       53 booster           (69.8; 84.6)         (45.6; 87.9)        (93.3; 100)        (328; 559) Post-              100%                   3145              100%                9016 139                                       59 booster(1)         (97.4; 100)          (2637; 3750)        (93.9; 100)       (7045; 11537) Post-dose            98.8%                  1470              92.3%               195 163                                       52
1(1)            (95.6; 99.9)         (1187; 1821)        (81.5; 97.9)       (118; 323) Pre-               88.5%                  106               98.4%               389 Y                     131                                       61 booster           (81.8; 93.4)         (76.4; 148)         (91.2; 100)        (292; 518) Post-              100%                   2749              100%                5978 139                                       69 booster(1)         (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. Although similar responses to groups A and C were observed with both dosing schedules, a single primary dose in infants at 6 months was associated with lower hSBA titres to groups W-135 and Y as measured by the 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.


   Immunogenicity in toddlers aged 12-23 months
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 to those elicited by a licensed MenC-CRM vaccine in terms of the percentage of subjects with rSBA titres ≥8. In Study MenACWY-TT-039, hSBA was also measured as a secondary endpoint. Results are shown in Table 4.

Table 4: SBA* titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged 12-23 months (Studies MenACWY-TT-039/040)
Study MenACWY-TT-039(1)                           Study MenACWY-TT-040(2) Meningo
Vaccine                   rSBA*                           hSBA*                             rSBA* -coccal group                 ≥8          GMT                 ≥8          GMT                   ≥8          GMT group                      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%          691 121                               116                              114 vaccine          (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 the response up to 5 years following 1 or 2 doses (given 2 months apart) of Nimenrix in toddlers aged 12 to 14 months. One month following one or two doses Nimenrix elicited rSBA titres against all four meningococcal 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 percentage of 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 of subjects with hSBA titre ≥8 when two doses were given compared with one. At Year 5 only a small difference in antibody persistence between one and two doses was observed, in terms of percentages of subjects with hSBA titres ≥8 against all groups. Antibody persistence was observed at Year 5 against 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 were 61.5% and 54.2%, respectively. For group A, 27.9% and 17.9% of subjects receiving one or two doses, 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 dose administered to toddlers aged 12-14 months and persistence up to 5 years (Study MenACWY-TT-104)
Meningo-      Nimenrix                              rSBA*                               hSBA** Time coccal         dose                             ≥8             GMT                  ≥8          GMT point(1)     N                                     N group         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 dose
46.9%           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
A                                          (49.8; 67.1)   (30.7; 71.5)         (17.1; 40.8)    (3.1; 6.2) 
96.8%           1275                97.0%           133
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)
2 doses                          70.6%            76.6                35.5%            6.4
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 dose
35.4%             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                                   69
(95.3; 99.8)    (522; 783)          (94.8; 100)    (1278; 2404)
2 doses                          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)
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)

Meningo-      Nimenrix                                 rSBA*                                 hSBA** Time coccal         dose                                ≥8               GMT                  ≥8          GMT point(1)     N                                         N group         group                             (95% CI)          (95% CI)            (95% CI)     (95% CI) 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)

65.3%              57.2                95.8%            209.0
Year 1       167                                       72
(57.5; 72.5)      (39.9; 82.0)         (88.3; 99.1)   (149.9; 291.4)
1 dose
59.2%              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)
2 doses                                                                   98.5%
77.6%               123                                 232.6
Year 1       143                                       65      (91.7; (69.9; 84.2)      (82.7; 183)                         (168.3; 321.4)
100.0)
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 dose
61.9%              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 doses                               79.7%            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)
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 laboratories
 rSBA and hSBA titres were determined over a period of 10 years in children initially vaccinated with one 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 a single booster dose of Nimenrix administered 10 years following the initial vaccination with Nimenrix or 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 aged 12-23 months, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-027/032/100)
Meningo                                                   rSBA*                                hSBA** Vaccine     Time point coccal                                               ≥8             GMT                   ≥8              GMT group                         N                                  N group                                            (95% CI)         (95% CI)            (95% CI)         (95% CI) 100%              3707               91.2%              59.0
Month 1(1)           222                                217
(98.4; 100)     (3327; 4129)        (86.7; 94.6)      (49.3; 70.6)
64.4%             35.1               52.3%               8.8
Year 4(2)             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%               4.2 62                                 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)
97.8%              110               97.8%              370
Year 4(2)             45                                 45
(88.2; 99.9)     (62.7; 192)        (88.2; 99.9)       (214; 640)
77.6%             48.9               91.7%              216
Nimenrix Year 5(2)               49                                 48 (63.4; 88.2)     (28.5; 84.0)       (80.0; 97.7)       (124; 379)
Year 10(3)                   82.3%              128               91.7%              349 62                                 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
98.5%              415               72.1%              21.2
Month 1(1)           68                                  68
(92.1; 100)       (297; 580)        (59.9; 82.3)      (13.9; 32.3)
80.0%              137               70.0%              91.9
Year 4(2)             10                                 10
(44.4; 97.5)     (22.6; 832)        (34.8; 93.3)       (9.8; 859)
MenC-
63.6%             26.5               90.9%              109
CRM      Year 5(2)             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%              117 16                                 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
Month 1(1)           222                                177
(98.4; 100)     (4870; 5976)        (73.0; 85.3)      (29.7; 50.6)
60.0%             50.8               84.4%              76.9
Year 4(2)             45                                 45
(44.3; 74.3)     (24.0; 108)        (70.5; 93.5)      (44.0; 134)
34.7%             18.2               82.6%              59.7
W-135 Nimenrix Year 5(2)                    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%               7.7 62                                 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)
100%              2824               66.7%              24.4
Month 1(1)           222                                201
(98.4; 100)     (2529; 3153)        (59.7; 73.1)      (18.6; 32.1)
62.2%             44.9               87.8%              74.6
Year 4(2)             45                                 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%               9.1 62                                 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 vaccination and the booster ATP cohort. Subjects with a suboptimal response to meningococcal group C (defined as SBA titre 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 PHE laboratories 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.

Persistence of booster response
Study MenACWY-TT-102 evaluated the persistence of SBA titres up to 6 years after a booster dose of Nimenrix or MenC-CRM 197 administered in Study MenACWY-TT-048 to children who initially received the same vaccine at 12 to 23 months of age in Study MenACWY-TT-039. A single booster dose 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 aged 12-23 months, persistence at 4 years and response following a booster 4 years after initial vaccination, 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            GMT group                           N                                     N group                                             (95% CI)       (95% CI)               (95% CI)        (95% CI) 99.7%          2205                   77.2%            19.0
Month 1(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) booster)
A       Nimenrix                                  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%              13.2 137                                   135 booster dose(4)             (83.4; 94.3)     (163; 322)           (44.6; 62.0)      (9.6; 18.3) 6 years after                 92.5%              297                58.5%              14.4 134                                   130 booster 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%              337 137                                   136 booster dose(4)             (72.6; 86.6)     (48.1; 90.5)         (96.0; 100)       (261; 435) 6 years after                 71.6%              39.6               97.7%              259 134                                   130 booster dose(4)             (63.2; 79.1)     (28.6; 54.6)         (93.4; 99.5)      (195; 345) C
97.5%               212               81.9%              40.3
Month 1(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-      CRM 197 booster)
CRM                                      100%             3718                 100%             8646 (Post-booster)(2,3)   43                                    33 vaccine                                (91.8; 100)     (2596; 5326)          (89.4; 100)    (5887; 12699) 5 years after                 78.3%              47.3                100%              241 23                                    23 booster dose(4)             (56.3; 92.5)     (19.0; 118)          (85.2; 100)      (139; 420) 6 years after                 65.2%              33.0               95.7%              169 23                                    23 booster dose(4)             (42.7; 83.6)     (14.7; 74.2)         (78.1; 99.9)     (94.1; 305) 100%             2682                87.5%             48.9
Month 1(1)            354                                   336
(99.0; 100)     (2453; 2932)          (83.5; 90.8)    (41.2; 58.0)
W-135     Nimenrix 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)
Table 7:    rSBA and hSBA titres following a single dose of Nimenrix (or MenC-CRM) in toddlers aged 12-23 months, persistence at 4 years and response following a booster 4 years after initial vaccination, 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            GMT group                           N                                    N group                                             (95% CI)        (95% CI)             (95% CI)        (95% CI) 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%             327 137                                  136 booster dose(4)             (81.7; 93.2)    (130; 261)           (97.3; 100)      (276; 388) 6 years after                  85.8%            172                 98.5%            314 134                                  133 booster dose(4)             (78.7; 91.2)    (118; 251)           (94.7; 99.8)     (255; 388) 100%            2729                 79.3%            30.9
Month 1(1)            354                                  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                                  100%             4585                100%              6776 (Post-booster)(2,3)   215                                  173
(98.3; 100)     (4129; 5093)         (97.9; 100)      (5961; 7701)
5 years after                 92.7%              265               97.8%               399 137                                  137 booster dose(4)             (87.0; 96.4)     (191; 368)          (93.7; 99.5)      (321; 495) 6 years after                 94.0%              260               97.7%               316 134                                  131 booster 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 PHE laboratories 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.

Immunogenicity in children aged 2-10 years

In Study MenACWY-TT-081, a single dose of Nimenrix was demonstrated to be non-inferior to another 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 the licensed ACWY-PS vaccine in terms of vaccine response to the four meningococcal groups as shown in Table 8.


Table 8: rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in children aged            2-10 years (Study MenACWY-TT-038)
Meningo                      Nimenrix(1)                               ACWY-PS vaccine(1) -coccal                   VR                GMT                         VR                  GMT N                                               N group                 (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 seropositive subjects (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-081 as shown in Table 9 (see section 4.4).

Table 9: rSBA and hSBA titres up to 44 months following Nimenrix (or MenC-CRM) in children aged 2-10 years at time of vaccination (Study MenACWY-TT-088)
Meningo                 Time                  rSBA*                         hSBA** Vaccine coccal                 point               ≥8           GMT               ≥8         GMT group                N                               N group               (months)          (95% CI)       (95% CI)        (95% CI)     (95% CI) 86.5%           196            25.6%         4.6
32      193                              90
(80.9; 91.0)   (144; 267)      (16.9; 35.8)  (3.3; 6.3)
A      Nimenrix
85.7%           307            25.8%         4.8
44      189                              89
(79.9; 90.4)   (224; 423)      (17.1; 36.2)  (3.4; 6.7)
64.6%           34.8           95.6%         75.9
32      192                              90
(57.4; 71.3) (26.0; 46.4)      (89.0; 98.8) (53.4; 108)
Nimenrix
37.0%           14.5           76.8%         36.4
44      189                              82
(30.1; 44.3) (10.9; 19.2)      (66.2; 85.4) (23.1; 57.2)
C
76.8%           86.5           90.9%         82.2
MenC-        32       69                              33
(65.1; 86.1)   (47.3; 158)     (75.7; 98.1) (34.6; 196)
CRM
45.5%           31.0           64.5%         38.8 vaccine      44       66                              31
(33.1; 58.2) (16.6; 58.0)      (45.4; 80.8) (13.3; 113)
77.2%           214            84.9%         69.9
32      193                              86
(70.6; 82.9)   (149; 307)      (75.5; 91.7) (48.2; 101)
W-135 Nimenrix
68.3%           103            80.5%         64.3
44      189                              87
(61.1; 74.8)   (72.5; 148)     (70.6; 88.2) (42.7; 96.8)
81.3%           227            81.3%         79.2
32      193                              91
(75.1; 86.6)   (165; 314)      (71.8; 88.7) (52.5; 119)
Y      Nimenrix
62.4%           78.9           82.9%         127
44      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 who were 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 aged 6-10 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) ococcal group                  ≥8             GMT                     ≥8              GMT group                  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%              2.5 35                                     35 vaccine            (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%              7.7 38                                     31 vaccine            (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%              3.4 35                                     31 vaccine            (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%              9.3 32                                     36 vaccine            (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 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 a single booster dose 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 aged                   2-10 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-027/032/100)
Meningo-                                                    rSBA*                                   hSBA** Vaccine coccal                  Time point                    ≥8               GMT                      ≥8           GMT group                          N                                        N group                                             (95% CI)          (95% CI)                (95% CI)       (95% CI) 100%               7301                   81.1%           57.0
Month 1(1)            225                                    111(5)
(98.4; 100)      (6586; 8093)             (72.5; 87.9)   (40.3; 80.6) 90.8%               141
Year 5(2)             98                                     n/a(6)        --             -- (83.3; 95.7)      (98.2; 203)
79.6%               107                  41.1%             6.5
Nimenrix Year 6(3)              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%             4.5 73                                      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) A
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) 15.4%                4.7
Year 5(2)               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%             6.2 17                                      17
(Pre-booster)                  (6.8; 49.9)      (3.3; 19.3)             (10.3; 56.0)    (2.4; 15.7) 100%               6414                   100%             211
(Post-booster)(3,4)   17                                      17
(80.5; 100)     (3879; 10608)             (80.5; 100)     (131; 340)
Table 11:         rSBA and hSBA titres following a single dose of Nimenrix (or ACWY-PS) in children aged                   2-10 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-027/032/100)
Meningo-                                                    rSBA*                                   hSBA** Vaccine coccal                  Time point                    ≥8               GMT                      ≥8          GMT group                          N                                        N group                                             (95% CI)          (95% CI)                (95% CI)      (95% CI) 100%                2435                  89.7%          155
Month 1(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)
82.7%                193                 93.8%              427
Nimenrix Year 6(3)              98                                      97 (73.7; 89.6)       (121; 308)             (87.0; 97.7)     (261; 700) Year 10(3)                     85.1%                181                 91.8%              222 74                                      73
(Pre-booster)               (75.0; 92.3)       (106; 310)             (83.0; 96.9)     (129; 380) 100%                4020                  100%            15544
(Post-booster)(3,4)   74                                      71
(95.1; 100)      (3319; 4869)             (94.9; 100)    (11735; 20588) C
100%                 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%              99.1 17                                      17
(Pre-booster)                 (50.1; 93.2)      (28.9; 320)             (80.5; 100)       (35.8; 274) 100%               15101                   94.1            44794
(Post-booster)(3,4)   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)
73.5%                265                 81.5%              62.5
Nimenrix Year 6(3)              98                                      92 (63.6; 81.9)       (155; 454)             (72.1; 88.9)     (42.0; 93.1) Year 10(3)                     68.9%                206                 61.0%              17.5 74                                      59
(Pre-booster)               (57.1; 79.2)       (109; 392)             (47.4; 73.5)     (10.5; 29.2) 100%               27944                  100%             6965
(Post-booster)(3,4)   74                                      74
(95.1; 100)    (22214; 35153)             (95.1; 100)     (5274; 9198) W-135
100%                2186                 34.3%               5.8
Month 1(1)            75                                     35(5)
(95.2; 100)      (1723; 2774)             (19.1; 52.2)      (3.3, 9.9) 0%                 4.0
Year 5(2)             13                                     n/a(6)        --              -- (0.0; 24.7)        (4.0; 4.0)
ACWY-
12.5%                7.6                  30.4%             7.0
PS    Year 6(3)               24                                      23 (2.7; 32.4)       (3.7; 15.6)            (13.2; 52.9)     (2.9; 16.9) vaccine
Year 10(3)                       23.5%               15.4                  26.7%             4.1 17                                      15
(Pre-booster)                  (6.8; 49.9)       (4.2; 56.4)             (7.8; 55.1)      (2.0; 8.5) 94.1%              10463                  100%              200
(Post-booster)(3,4)   17                                      15
(71.3; 99.9)    (3254; 33646)             (78.2; 100)      (101; 395) 

Table 11:         rSBA and hSBA titres following a single dose of Nimenrix (or ACWY-PS) in children aged                   2-10 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-027/032/100)
Meningo-                                                  rSBA*                                    hSBA** Vaccine coccal                  Time point                   ≥8             GMT                       ≥8              GMT group                          N                                      N group                                            (95% CI)         (95% CI)                (95% CI)          (95% CI) 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%              35.7 74                                    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
100%             1410                    43.8%              12.5
Month 1(1)           75                                   32(5)
(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%               7.8 17                                    14
(Pre-booster)             (3.8; 43.4)      (3.5; 30.2)             (12.8; 64.9)      (2.5; 24.4) 100%             6959                    100%               454
(Post-booster)(3,4) 17                                     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 a suboptimal response to meningococcal group C (defined as SBA titre 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 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 PHE laboratories 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.

Immunogenicity in adolescents aged 11-17 years and adults aged ≥18 years 
In two clinical studies, conducted in adolescents aged 11-17 years (Study MenACWY-TT-036) and in adults 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 of vaccine response as shown in Table 12.


Table 12:       rSBA* titres following a single dose of Nimenrix (or ACWY-PS) in adolescents aged 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) coccal group                     VR                 GMT                          VR               GMT group                        N                                              N (95% CI)             (95% CI)                    (95% CI)          (95% CI) Nimenrix                  85.4%                 5928                       80.1%             3625 553                                            743
(82.1; 88.2)        (5557; 6324)                 (77.0; 82.9)     (3372; 3897) A
ACWY-PS                    77.5%                 2947                       69.8%             2127 191                                            252 vaccine               (70.9; 83.2)        (2612; 3326)                 (63.8; 75.4)     (1909; 2370) Nimenrix                  97.4%                13110                       91.5%             8866 642                                            849
(95.8; 98.5)       (11939; 14395)                (89.4; 93.3)     (8011; 9812) C
ACWY-PS                    96.7%                 8222                       92.0%             7371 211                                            288 vaccine               (93.3; 98.7)        (6807; 9930)                 (88.3; 94.9)     (6297; 8628) Nimenrix                  96.4%                 8247                       90.2%             5136 639                                            860
(94.6; 97.7)        (7639; 8903)                 (88.1; 92.1)     (4699; 5614) W-135
ACWY-PS                    87.5%                 2633                       85.5%             2461 216                                            283 vaccine               (82.3; 91.6)        (2299; 3014)                 (80.9; 89.4)     (2081; 2911) Nimenrix                  93.8%                14086                       87.0%             7711 657                                            862
(91.6; 95.5)       (13168; 15069)                (84.6; 89.2)     (7100; 8374) Y
ACWY-PS                    78.5%                 5066                       78.8%             4314 219                                            288 vaccine               (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 laboratories
 rSBA 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 rSBA titres 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 dose of 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 aged 11-17 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-036/043/101)
Meningo-                                          Nimenrix                                  ACWY-PS vaccine Time point coccal                                        ≥8             GMT                              ≥8           GMT N                                               N group                                     (95% CI)         (95% CI)                       (95% CI)       (95% CI) 100%              5929                          99.6%          2947
Month 1(1)           674                                             224 (99.5; 100)      (5557; 6324)                   (97.5; 100)   (2612; 3326) 92.9%              448                          82.7%           206
Year 3(2)            449                                             150 (90.1; 95.1)      (381; 527)                    (75.6; 88.4)   (147; 288) 97.5%              644                          93.0%           296
A       Year 5(2)            236                                             86 (94.5; 99.1)      (531; 781)                    (85.4; 97.4)   (202; 433) Year 10(3)                       85.2%              248                          80.4%           143 162                                             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 aged 11-17 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-036/043/101)
Meningo-                                         Nimenrix                             ACWY-PS vaccine Time point coccal                                       ≥8               GMT                       ≥8              GMT N                                       N group                                    (95% CI)           (95% CI)                (95% CI)          (95% CI) 100%               13110                   100%               8222
Month 1(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) 88.6%                249                   87.1%               366
C       Year 5(2)            236                                      85 (83.8; 92.3)         (194; 318)             (78.0; 93.4)       (224; 599) Year 10(3)                     90.1%                244                   82.4%               177 162                                      51
(Pre-booster)             (84.5; 94.2)         (182; 329)             (69.1; 91.6)      (86.1; 365) 100%                8698                   100%               3879
(Post-booster)(3,4) 162                                      51
(97.7; 100)      (7391 10235)              (93.0; 100)      (2715; 5544) 99.9%               8247                   100%               2633
Month 1(1)           678                                     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%              16.4 162                                      51
(Pre-booster)             (64.0; 78.4)        (97.6; 217)             (29.3; 57.8)       (9.2; 29.4) 100%               11243                   100%               3674
(Post-booster)(3,4) 162                                      51
(97.7; 100)      (9367; 13496)             (93.0; 100)      (2354; 5734) 100%               14087                   100%               5066
Month 1(1)           677                                     224
(99.5; 100)     (13168; 15069)             (98.4; 100)      (4463; 5751) 93.1%                740                   58.0%              69.6
Year 3(2)            449                                     150
(90.3; 95.3)         (620; 884)             (49.7; 66.0)      (44.6; 109) 96.6%               1000                   66.3%               125
Y       Year 5(2)            236                                      86 (93.4; 98.5)        (824; 1214)             (55.3; 76.1)      (71.2; 219) Year 10(3)                     90.7%                447                   49.0%              32.9 162                                      51
(Pre-booster)             (85.2; 94.7)         (333; 599)             (34.8; 63.4)      (17.1; 63.3) 100%                7585                   98.0%              3296
(Post-booster)(3,4) 162                                      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 PHE laboratories in UK for the subsequent sampling time points.
 hSBA persistence was evaluated up to 5 years after vaccination in adolescents and adults initially vaccinated 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 aged 11-25 years and persistence up to 5 years following vaccination (Studies MenACWY-TT- 052/059)
Meningococcal
Time point          N        ≥8 (95% CI)             GMT (95% CI) group
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 laboratories
 rSBA 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 rSBA titres 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 booster dose 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 and adults aged 11-55 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-015/020/099) Meningo-                                             Nimenrix                        ACWY-PS vaccine coccal        Time point                         ≥8              GMT                   ≥8          GMT N                                     N group                                        (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%          75.1 155                                       52
(Pre-booster)                    (70.7; 84.3)      (108; 219)          (56.9; 82.9)  (41.4; 136) 100%               4060               100%          3585
(Post-booster)(3,4)    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)
76.7%               126               41.2%          16.7
Year 4(2)                  43                                    17
(61.4; 88.2)      (61.6; 258)         (18.4; 67.1)  (5.7; 48.7)
72.5%              78.5               38.9%          17.3
C       Year 5(2)                  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%          212
154                                       52
(Pre-booster)                    (85.2; 94.9)      (141; 264)          (76.6; 95.6)  (110; 412) 100%              13824               98.1%         3444
(Post-booster)(3,4)    155                                       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 and adults aged 11-55 years, persistence up to 10 years, and post-booster administered 10 years following initial vaccination (Studies MenACWY-TT-015/020/099) Meningo-                                         Nimenrix                         ACWY-PS vaccine coccal        Time point                     ≥8              GMT                    ≥8           GMT N                                      N group                                    (95% CI)          (95% CI)             (95% CI)       (95% CI) 99.7%              8577                100%            2970
Month 1(1)           340                                    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%           10.9 154                                     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)
86.0%               443                47.1%           30.7
Year 4(2)             43                                     17
(72.1; 94.7)        (230; 853)         (23.0; 72.2)     (9.0; 105)
92.2%               770                63.2%           74.1
Y      Year 5(2)             51                                     19 (81.1; 97.8)       (439; 1351)         (38.4; 83.7)    (21.9; 250)
Year 10(3)                     86.4%               364                61.5%           56.0 154                                     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 vaccination and 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 PHE laboratories 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). The percentage of subjects with rSBA titres (measured at GSK’s laboratories) ≥128 before vaccination ranged from 45% (group C) to 62% (group Y). Overall, at 1 month post-vaccination the percentage of vaccines 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 from 90% (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 a quadrivalent conjugate meningococcal vaccine (MenACWY-TT) was studied in subjects from 12 months of age onwards who received a booster vaccination. Robust anamnestic responses to the antigen(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 was compared to the immunogenicity of Nimenrix administered to age-matched subjects who had not been vaccinated with any meningococcal vaccine in the preceding 10 years. An immune response (rSBA titre ≥8) was observed against all four meningococcal groups in all subjects regardless of the meningococcal vaccine history.
The rSBA GMTs were significantly lower in the subjects who had received a dose of ACWY-PS vaccine 30-42 months prior to Nimenrix, however 100% of subjects achieved rSBA titres ≥8 for all four meningococcal groups (A, C, W-135, Y) (see section 4.4).

Children (2-17 years) with anatomical or functional asplenia

Study MenACWY-TT-084 compared immune responses to two doses of Nimenrix given 2 months apart between 43 subjects aged 2-17 years with anatomic or functional asplenia subjects and 43 age-matched subjects with normal splenic function. One month after the first vaccine dose and 1 month after the second dose similar percentages of subjects in the two groups had rSBA titres ≥8 and ≥128 and hSBA titres ≥4 and ≥8.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Not applicable.