Vaccine Information: Prevnar 20 (Page 4 of 6)
14.2 Prevnar 20 Clinical Trials in Individuals 6 Weeks Through 15 Months of Age
Immunogenicity of Prevnar 20 in Individuals 6 Weeks Through 15 Months of Age
Prevnar 20 effectiveness against invasive pneumococcal disease in individuals 6 weeks through 15 months of age was demonstrated based on comparisons of serotype-specific antibody responses at 1 month after Dose 3 and 1 month after Dose 4 of Prevnar 20 to the antibody responses after vaccination with Prevnar 13.
Antibody responses elicited by Prevnar 20 and Prevnar 13 in these age groups were measured using a serotype-specific multiplex direct-binding Luminex® immunoassay (dLIA), designed to determine the concentration of serotype-specific polysaccharide-binding IgG antibodies, and OPA assays to measure serotype-specific functional OPA titers for the 20 pneumococcal serotypes of Prevnar 20. A serotype-specific IgG antibody concentration corresponding to ≥0.35 µg/mL using the World Health Organization (WHO) enzyme linked immunosorbent assay (ELISA) has been used as the threshold value for the clinical evaluation of pneumococcal conjugate vaccines when measured one month after Dose 3 of the 4-dose immunization series. The dLIA, used to measure the IgG antibody concentration, was bridged to the WHO ELISA to establish dLIA specific threshold values for each vaccine serotype that correspond to the established ≥0.35 µg/mL WHO ELISA threshold value.
In Study 8, a multicenter, randomized, active-controlled, double-blind trial, participants were randomized in a 1:1 ratio to receive Prevnar 20 (N=1004) or Prevnar 13 (N=993) in a 4-dose schedule; vaccine was administered at 2, 4, 6, and 12 through 15 months of age. Pediarix and Hiberix were administered concomitantly with each of the 3 infant doses. M-M-R II and VARIVAX were administered with the fourth dose [see Adverse Reactions (6.1) and Clinical Studies (14.3)].
Study 8 assessed serotype-specific IgG response rates, IgG geometric mean concentrations (GMCs) and OPA GMTs measured at one month after Dose 3 and one month after Dose 4 for all 20 serotypes contained in Prevnar 20. For each of the 13 matched serotypes, IgG response in the Prevnar 20 group were compared with the corresponding response in the Prevnar 13 group. For the 7 additional serotypes (serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F), IgG response in the Prevnar 20 group were compared with the lowest response among the 13 matched vaccine serotypes excluding serotype 3 in the Prevnar 13 group.
Pneumococcal IgG Antibody Responses Following 3 Doses of Prevnar 20
IgG antibody responses following Prevnar 20 were noninferior to those following Prevnar 13 for 8 of the 13 matched serotypes and 6 of the 7 additional serotypes, as assessed by the percentage of participants meeting the predefined serotype-specific IgG concentration one month after Dose 3, using a 10% noninferiority criterion (the lower bound of the 2-sided 95% CI for the difference in percentages [Prevnar 20 minus Prevnar 13] greater than -10%). Five of the 13 matched serotypes (serotypes 1, 3, 4, 9V and 23F) did not meet the pre-specified noninferiority criterion, as the lower bounds of the 2-sided 95% CIs for the difference in percentages (Prevnar 20 minus Prevnar 13) were -12.1%, -20.1%, -12.0%, -11.3%, and -11.4% respectively. One additional serotype (serotype 12F) also did not meet the NI criterion when compared to serotype 23F (the Prevnar 13 serotype with the lowest percentage excluding serotype 3) in the Prevnar 13 group, the lower bound of the 2-sided 95% CI for the difference in percentage (Prevnar 20 minus lowest Prevnar 13) was -41.6% (Table 9).
Additional IgG GMC data at one month after Dose 3 and OPA data at one month after Dose 3, presented in Tables 10 and 12 respectively, support the effectiveness of Prevnar 20 for each of the 6 serotypes that failed to meet the pre-specified non-inferiority criterion.
Abbreviation: IgG = immunoglobulin G. | |||
Note: The predefined IgG concentration was ≥0.35 µg/mL for all serotypes except for serotypes 5, 6B, 12F, and 19A which were ≥0.23 µg/mL, ≥0.10 µg/mL, ≥0.69 µg/mL and ≥0.12 µg/mL respectively. | |||
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Prevnar 20 N † =831-833 | Prevnar 13 N † =801-802 | Prevnar 20 minus Prevnar 13 | |
% (95% CI ‡ ) | % (95% CI ‡ ) | ||
Serotypes | |||
1 | 79.8 (76.9, 82.5) | 88.4 (86.0, 90.5) | -8.6 (-12.1, -5.1) |
3 | 52.1 (48.6, 55.5) | 67.6 (64.2, 70.8) | -15.5 (-20.1, -10.8) |
4 | 79.7 (76.8, 82.4) | 88.2 (85.7, 90.3) | -8.4 (-12.0, -4.9) |
5 | 82.5 (79.7, 85.0) | 86.8 (84.2, 89.1) | -4.3 (-7.8, -0.8) |
6A | 93.5 (91.6, 95.1) | 95.9 (94.3, 97.2) | -2.4 (-4.6, -0.2) |
6B | 88.3 (85.9, 90.4) | 92.4 (90.3, 94.1) | -4.1 (-7.0, -1.2) |
7F | 96.6 (95.2, 97.8) | 97.6 (96.3, 98.6) | -1.0 (-2.7, 0.7) |
9V | 81.9 (79.1, 84.4) | 89.8 (87.5, 91.8) | -7.9 (-11.3, -4.6) |
14 | 93.4 (91.5, 95.0) | 94.1 (92.3, 95.7) | -0.8 (-3.1, 1.6) |
18C | 92.6 (90.6, 94.2) | 93.1 (91.2, 94.8) | -0.6 (-3.1, 1.9) |
19A | 97.1 (95.7, 98.1) | 98.1 (96.9, 98.9) | -1.0 (-2.6, 0.5) |
19F | 96.9 (95.5, 98.0) | 96.6 (95.1, 97.8) | 0.2 (-1.5, 2.0) |
23F | 77.9 (74.9, 80.7) | 85.5 (82.9, 87.9) | -7.6 (-11.4, -3.9) |
Additional Serotypes # | |||
8 | 96.8 (95.3, 97.9) | 11.2 (8.6, 14.0) | |
10A | 82.2 (79.5, 84.8) | -3.3 (-6.9, 0.3) | |
11A | 92.7 (90.7, 94.4) | 7.1 (4.2, 10.2) | |
12F | 48.0 (44.6, 51.5) | -37.5 (-41.6, -33.3) | |
15B | 98.2 (97.0, 99.0) | 12.7 (10.2, 15.4) | |
22F | 98.3 (97.2, 99.1) | 12.8 (10.3, 15.5) | |
33F | 86.7 (84.2, 88.9) | 1.1 (-2.2, 4.5) |
At 1 month after Dose 3, IgG GMCs in the Prevnar 20 group were noninferior to the corresponding IgG GMCs in the Prevnar 13 group for all 20 vaccine serotypes, including the 6 serotypes that missed the noninferiority criterion based on the percentage of participants meeting pre-defined IgG concentrations at one month after Dose 3. For each of the 13 matched serotypes, IgG GMCs in the Prevnar 20 group were noninferior to the corresponding IgG GMCs in the Prevnar 13 group. For each of the 7 additional serotypes, IgG GMCs in the Prevnar 20 group were noninferior to the IgG GMC for serotype 19A (the lowest result among the 13 matched vaccine serotypes excluding serotype 3) in the Prevnar 13 group (Table 10).
Abbreviations: GMC = geometric mean concentration; IgG = immunoglobulin G; LLOQ = lower limit of quantitation. | |||
Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. | |||
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Pneumococcal Serotype | Prevnar 20 N † =831-833 | Prevnar 13 N † =801-802 | Prevnar 20/Prevnar 13 |
Serotype | |||
1 | 0.74 (0.70, 0.79) | 1.14 (1.06, 1.22) | 0.65 (0.59, 0.72) |
3 | 0.36 (0.33, 0.38) | 0.51 (0.48, 0.55) | 0.70 (0.64, 0.76) |
4 | 0.75 (0.70, 0.81) | 1.08 (1.00, 1.17) | 0.70 (0.63, 0.78) |
5 | 0.66 (0.61, 0.71) | 0.96 (0.88, 1.04) | 0.69 (0.61, 0.77) |
6A | 1.95 (1.81, 2.10) | 2.69 (2.48, 2.92) | 0.72 (0.65, 0.81) |
6B | 0.61 (0.55, 0.68) | 1.02 (0.91, 1.14) | 0.60 (0.51, 0.70) |
7F | 1.71 (1.62, 1.81) | 2.29 (2.16, 2.43) | 0.75 (0.69, 0.81) |
9V | 0.87 (0.81, 0.93) | 1.21 (1.12, 1.30) | 0.72 (0.65, 0.80) |
14 | 2.16 (2.01, 2.33) | 2.72 (2.51, 2.95) | 0.79 (0.71, 0.89) |
18C | 1.31 (1.23, 1.39) | 1.71 (1.59, 1.84) | 0.77 (0.70, 0.84) |
19A | 0.72 (0.67, 0.76) | 0.91 (0.85, 0.97) | 0.79 (0.72, 0.86) |
19F | 1.59 (1.50, 1.67) | 2.00 (1.88, 2.12) | 0.79 (0.73, 0.86) |
23F | 0.82 (0.75, 0.90) | 1.25 (1.14, 1.37) | 0.66 (0.58, 0.75) |
Additional Serotypes # | |||
8 | 1.80 (1.70, 1.91) | 1.98 (1.81, 2.16) | |
10A | 1.21 (1.09, 1.33) | 1.32 (1.18, 1.49) | |
11A | 1.39 (1.30, 1.48) | 1.52 (1.39, 1.67) | |
12F | 0.55 (0.50, 0.60) | 0.60 (0.54, 0.67) | |
15B | 4.40 (4.11, 4.71) | 4.82 (4.39, 5.30) | |
22F | 3.71 (3.45, 3.99) | 4.06 (3.68, 4.48) | |
33F | 1.49 (1.36, 1.64) | 1.64 (1.46, 1.83) |
Pneumococcal IgG Antibody Responses Following 4 Doses of Prevnar 20
For each of the 13 matched serotypes, IgG GMCs in the Prevnar 20 group were noninferior to the corresponding IgG GMCs in the Prevnar 13 group. For each of the 7 additional serotypes, IgG GMCs in the Prevnar 20 group were noninferior to the IgG GMC for serotype 1 (the lowest result among the 13 matched vaccine serotypes excluding serotype 3) in the Prevnar 13 group (Table 11).
Prevnar 20 N † =753-755 | Prevnar 13 N † =744-745 | Prevnar 20/Prevnar 13 | |
---|---|---|---|
GMC ‡ (95% CI ‡ ) | GMC ‡ (95% CI ‡ ) | GMC Ratio § (95% CI § ¶ ) | |
Abbreviations: GMC = geometric mean concentration; IgG = immunoglobulin G; LLOQ = lower limit of quantitation.Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. | |||
| |||
Serotypes | |||
1 | 1.47 (1.37, 1.57) | 2.12 (1.97, 2.27) | 0.69 (0.63, 0.76) |
3 | 0.56 (0.53, 0.60) | 0.85 (0.80, 0.90) | 0.66 (0.61, 0.73) |
4 | 3.77 (3.52, 4.04) | 4.84 (4.50, 5.22) | 0.78 (0.70, 0.86) |
5 | 1.87 (1.74, 2.00) | 2.51 (2.33, 2.70) | 0.74 (0.67, 0.82) |
6A | 9.01 (8.45, 9.61) | 11.69 (10.91, 12.53) | 0.77 (0.70, 0.85) |
6B | 4.01 (3.70, 4.35) | 5.74 (5.27, 6.24) | 0.70 (0.62, 0.79) |
7F | 3.91 (3.70, 4.14) | 5.18 (4.88, 5.49) | 0.76 (0.70, 0.82) |
9V | 3.44 (3.23, 3.67) | 4.30 (4.02, 4.59) | 0.80 (0.73, 0.88) |
14 | 5.68 (5.27, 6.12) | 6.34 (5.88, 6.83) | 0.90 (0.81, 1.00) |
18C | 3.46 (3.24, 3.70) | 4.69 (4.34, 5.05) | 0.74 (0.67, 0.82) |
19A | 3.53 (3.30, 3.77) | 4.13 (3.84, 4.45) | 0.85 (0.77, 0.94) |
19F | 5.01 (4.68, 5.36) | 5.79 (5.36, 6.25) | 0.86 (0.78, 0.96) |
23F | 3.95 (3.63, 4.31) | 6.18 (5.66, 6.75) | 0.64 (0.57, 0.72) |
Additional Serotypes # | |||
8 | 3.97 (3.73, 4.22) | 1.87 (1.71, 2.06) | |
10A | 6.22 (5.75, 6.72) | 2.94 (2.64, 3.26) | |
11A | 3.53 (3.31, 3.78) | 1.67 (1.51, 1.84) | |
12F | 1.85 (1.73, 1.99) | 0.88 (0.79, 0.97) | |
15B | 12.59 (11.78, 13.45) | 5.95 (5.39, 6.55) | |
22F | 10.60 (9.92, 11.33) | 5.01 (4.54, 5.52) | |
33F | 9.31 (8.71, 9.96) | 4.40 (3.99, 4.85) |
Opsonophagocytic Activity Responses After 3 and 4 doses of Prevnar 20
Serotype-specific OPA GMTs at 1 month after Dose 3 and 1 month after Dose 4 were descriptively evaluated in a subset of participants who had received Prevnar 20 and Prevnar 13 in Study 8 (Table 12). For serotypes 1, 3, 4, 9V, 23F and 12F, for which non-inferiority was not met 1 month after Dose 3 (for the percentage of participants meeting the pre-defined serotype-specific IgG concentration), OPA GMTs at 1 month after Dose 3 were numerically similar across groups for the 5 matched serotypes and an OPA antibody response was generated to additional serotype 12F.
Abbreviations: GMT = geometric mean titer; LLOQ = lower limit of quantitation; OPA = opsonophagocytic activity. | ||||
Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. | ||||
Note: OPA titers were determined on serum from randomly selected subsets of participants assuring equal representation of both vaccine groups. | ||||
Prevnar 20 N † = 85-105 After Dose 3 | Prevnar 13 N † = 84-113 After Dose 3 | Prevnar 20 N † = 80-99 After Dose 4 | Prevnar 13 N † = 77-103 After Dose 4 | |
Serotypes | ||||
1 | 26 (21, 33) | 34 (27, 42) | 36 (27, 48) | 66 (50, 87) |
3 | 51 (43, 61) | 63 (53, 76) | 62 (49, 78) | 102 (86, 120) |
4 | 339 (252, 455) | 280 (207, 378) | 621 (435, 887) | 961 (714, 1294) |
5 | 32 (27, 39) | 39 (32, 47) | 55 (45, 67) | 69 (54, 87) |
6A | 910 (763, 1084) | 936 (757, 1156) | 1384 (1092, 1753) | 1767(1329, 2348) |
6B | 318 (242, 419) | 516 (409, 651) | 666 (489, 906) | 1211 (861, 1703) |
7F | 1222 (1020, 1465) | 1149 (926, 1424) | 2022 (1673, 2444) | 2099 (1741, 2531) |
9V | 661 (482, 906) | 594 (421, 838) | 2609 (1913, 3558) | 3210 (2500, 4123) |
14 | 415 (323, 535) | 420 (330, 535) | 667 (523, 850) | 593 (462, 761) |
18C | 1153 (910, 1460) | 996 (754, 1317) | 1973 (1472, 2643) | 2425 (1914, 3072) |
19A | 108 (78, 149) | 109 (79, 151) | 844 (622, 1145) | 1357 (1007, 1829) |
19F | 84 (67, 105) | 116 (90, 149) | 246 (179, 337) | 373 (272, 513) |
23F | 255 (186, 350) | 295 (215, 406) | 827 (554, 1235) | 1532 (1118, 2100) |
Additional Serotypes | ||||
8 | 665 (503, 880) | 18 (17, 20) | 1228 (901, 1673) | 26 (21, 31) |
10A | 2558 (1869, 3501) | 37 (33, 42) | 3674 (2746, 4916) | 57 (44, 74) |
11A | 289 (212, 395) | 50 (46, 55) | 2728 (1975, 3768) | 69 (53, 89) |
12F | 7677 (5952, 9901) | 28 (24, 33) | 9320 (7037, 12343) | 31 (26, 37) |
15B | 1560 (1090, 2233) | 18 (16, 22) | 3035 (2138, 4308) | 23 (17, 30) |
22F | 6797 (5170, 8936) | 9 (9, 9) | 11077 (7956, 15422) | 15 (11, 20) |
33F | 7388 (4803, 11365) | 198 (177, 220) | 19216 (13193, 27990) | 363 (292, 451) |
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