Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02 
Mechanism of action

Prevenar 20 contains 20 pneumococcal capsular polysaccharides all conjugated to a CRM197 carrier protein, which modifies the immune response to the polysaccharide from a T-cell independent response to a T-cell dependent response. The T-cell dependent response leads to both an enhanced antibody response and generation of memory B-cells, allowing for an anamnestic (booster) response on re-exposure to the bacteria.

Vaccination with Prevenar 20 induces serum antibody production and immunologic memory against the serotypes contained within the vaccine. In adults, the levels of circulating antibodies, and in paediatric populations the serotype-specific levels, that correlate with protection against pneumococcal disease have not been clearly defined.


Prevenar 20 effectiveness
No efficacy studies have been performed with Prevenar 20.

Approval of Prevenar 20 for the paediatric population is based on comparing the totality of the immune responses in infants after receiving Prevenar 20 to the immune responses after receiving Prevenar 13. The comparison, following the World Health Organization (WHO) guideline, included the percentage of participants with predefined IgG (immunoglobulin G) concentrations and IgG geometric mean concentrations (GMCs). This approach is largely based upon the observed relationship between immunogenicity and invasive pneumococcal disease (IPD) efficacy from 3 placebo-controlled trials with either Prevenar (7-valent pneumococcal conjugate vaccine) or the investigational 9-valent CRM197 conjugate polysaccharide vaccine conducted in Navajo and White Mountain Apache Indian infants (cluster randomised trial), infants in Soweto, South Africa, and infants in the Northern California Kaiser Permanente (NCKP) health organization in the United States (see Prevenar Efficacy and Prevenar 13 Effectiveness in Children below). The predefined IgG concentration corresponding to 0.35 µg/mL in the WHO enzyme-linked immunosorbent assay (ELISA) is only applicable at the population level and cannot be used to predict individual or serotype-specific protection against IPD.


Immunogenicity data
Prevenar 20 clinical trials in infants, children and adolescents
Two Phase 3 clinical trials (Study 1012, Study 1011) and one Phase 2 clinical trial (Study 1003) evaluated the immunogenicity of Prevenar 20 in a 3-dose and 4-dose series in infants. One Phase 3 
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trial (Study 1014) of children 15 months to less than 18 years of age evaluated a single dose of Prevenar 20.
Pneumococcal IgG immune responses following 3 doses of 3-dose vaccination series In Study 1012, the immunogenicity of Prevenar 20 was evaluated in infants when administered in a series of 2 infant doses and 1 toddler dose in infants enrolled from Europe and Australia. The study enrolled infants 2 months (≥42 to ≤112 days) of age and born at >36 weeks of gestation. Participants were randomised (1:1) to receive either Prevenar 20 or Prevenar 13 with the first dose given at 42 to 112 days of age, a second dose given approximately 2 months later, and the third dose given at approximately 11 to 12 months of age. Participants received concomitant vaccines at these visits.
Prevenar 20 elicited immune responses, as assessed by the percentage of participants with predefined IgG concentrations, IgG GMCs and OPA GMTs for all 20 serotypes contained in the vaccine. The observed IgG GMCs and percentage of participants with predefined IgG concentrations 1 month after the third (last) dose of Prevenar 20 were generally comparable to the Prevenar 13 group for the 13 matched serotypes and higher for the 7 additional serotypes (Table 3).
One month after the 2 infant doses the observed IgG GMCs were generally comparable for most serotypes to the Prevenar 13 group and the percentages of participants with predefined IgG concentrations for the 13 matched serotypes were generally lower in the Prevenar 20 group than the Prevenar 13 group (Table 4). The immune responses to the additional 7 serotypes were higher in the Prevenar 20 group than the Prevenar 13 group after the second dose.

Table 3. Percentages of Participants with Predefined Pneumococcal IgG Concentrations and Pneumococcal IgG GMCs (µg/mL) One Month after Dose 3 of a 3-Dose Series, Study 1012a IgG GMCs
Percentages of Participants with
Predefined IgG Concentrationsb
PREVENAR        Prevenar     Prevenar 20 –        Prevenar 20    Prevenar 13          Prevenar 20/ 20              13         Prevenar 13
Nc = 493-495   Nc = 501-502         Prevenar 13 c              c
N = 493-495     N = 501-
502
%             %       % (95% CId)            GMCe           GMCe            GMRe (95% CIe) 
Serotypes
1           97.2      98.2         -1.0 (-3.1, 0.9)        1.71          2.53             0.67 (0.60, 0.75) 3           82.6      93.2       -10.6 (-14.7, -6.7)       0.72          1.09             0.66 (0.59, 0.73) 4           99.2      99.2           0 (-1.4, 1.3)         4.11          5.36             0.77 (0.68, 0.87)
5           98.4      98.0          0.4 (-1.4, 2.2)        1.74          2.41             0.72 (0.64, 0.81) 6A           98.8      98.8           0 (-1.6, 1.5)         7.75          11.82            0.66 (0.57, 0.75) 6B           98.4      97.6          0.8 (-1.1, 2.7)        2.64          4.63             0.57 (0.48, 0.67) 7F           99.6      100.0        -0.4 (-1.5, 0.4)        3.61          4.93             0.73 (0.67, 0.80) 9V           99.2      98.8          0.4 (-1.0, 1.9)        3.68          5.04             0.73 (0.66, 0.81) 14           96.6      98.0         -1.5 (-3.7, 0.6)        4.52          5.66             0.80 (0.69, 0.92) 18C           99.2      98.2          1.0 (-0.5, 2.7)        2.71          3.61             0.75 (0.67, 0.84) 19A           99.6      99.6           0 (-1.1, 1.1)         4.51          5.49             0.82 (0.72, 0.93) 19F           99.6      99.4          0.2 (-0.9, 1.4)        6.19          8.08             0.77 (0.68, 0.87) 23F           96.4      97.2         -0.9 (-3.2, 1.4)        2.64          4.40             0.60 (0.52, 0.69)
Additional Serotypes
8         99.2             3.6    95.6 (93.4, 97.1)        3.57            0.03        113.37 (100.05, 128.46) 10A        97.8             1.6    96.2 (94.1, 97.6)        4.86            0.01        423.02 (372.25, 480.73) 11A        98.4             4.6    93.8 (91.3, 95.6)        3.74            0.02        229.66 (199.06, 264.96) 12F        96.6             0.2    96.4 (94.3, 97.7)        1.86            0.01        224.31 (204.73, 245.76) 15B        99.4             4.8    94.6 (92.3, 96.3)        13.09           0.02        527.47 (465.44, 597.77) 22F        99.2             1.4    97.8 (96.1, 98.8)        9.27            0.00       2193.09 (1908.27, 2520.41)

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33F           98.6           1.8        96.8 (94.8, 98.0)         6.37              0.01            530.53 (470.15, 598.66) Abbreviations: CI = confidence interval; GMC = geometric mean concentration; GMR = geometric mean ratio; IgG = immunoglobulin G; LLOQ = lower limit of quantitation.
Note: Noninferiority for a matched serotype was concluded if the lower bound of the 2-sided 95% CI for the percentage difference (Prevenar 20 - Prevenar 13) was > -10% or the lower bound of the 2-sided 95% CI for the GMR (Prevenar 20 to Prevenar 13) was >0.5 for that serotype.
Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.
a. Study 1012 was conducted in Europe and Australia.
b. The predefined IgG concentration was ≥0.35 µg/mL for all serotypes except for serotypes 5, 6B and 19A which were ≥0.23 µg/mL, ≥0.10 µg/mL and ≥0.12 µg/mL respectively.
c. N = Number of participants with valid IgG concentrations.
d. Two-sided CI based on the Miettinen and Nurminen method.
e. GMCs, GMRs and the associated 2-sided CIs were calculated by exponentiating the means and the mean differences (Prevenar 20 – Prevenar 13) of logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution).

Table 4. Percentage of Participants with Predefined Pneumococcal IgG Concentrations and Pneumococcal IgG GMCs (µg/mL) One Month after Dose 2 of a 3-Dose Series, Study 1012a Percentages of Participants With Predefined                                  IgG GMCs IgG Concentrationsb
Prevenar      Prevenar          Prevenar 20 –          Prevenar       Prevenar      Prevenar20/ Prevenar 13 20            13              Prevenar 13              20             13
Nc = 564-     Nc = 561-                                Nc = 564-      Nc = 561- 567           562                                      567            562 %             %             % (95% CId)             GMCe           GMCe              GMR (95% CIe) Serotypes
1       70.7            84.2         -13.5 (-18.3, -8.7)         0.57          0.93             0.61 (0.54, 0.69) 3       58.0            75.8        -17.9 (-23.2, -12.4)         0.41          0.58             0.71 (0.64, 0.79) 4       68.6            79.5         -11.0 (-16.0, -5.9)         0.55          0.92             0.60 (0.52, 0.69)
5       63.4            76.0         -12.6 (-17.8, -7.2)         0.34          0.56             0.60 (0.52, 0.70) 6A        59.5            73.7         -14.1 (-19.5, -8.6)         0.45          0.84             0.54 0.45, 0.65) 6B       20.7            36.5        -15.8 (-21.0, -10.6)         0.03          0.06             0.51 (0.43, 0.61) 7F       87.6            90.2           -2.6 (-6.3, 1.1)          1.02          1.41             0.72 (0.64, 0.80) 9V        60.2            74.6         -14.3 (-19.7, -8.9)         0.45          0.77             0.59 (0.50, 0.69) 14       78.6            81.9           -3.3 (-7.9, 1.4)          1.05          1.28             0.82 (0.70, 0.96) 18C       71.0            76.5          -5.5 (-10.6, -0.4)         0.69          0.87             0.79 (0.67, 0.92) 19A       92.2            94.0           -1.7 (-4.8, 1.3)          0.67          1.13             0.59 (0.51, 0.69) 19F       94.3            95.7           -1.4 (-4.0, 1.2)          2.21          3.06             0.72 (0.64, 0.82) 23F       23.5            41.8        -18.3 (-23.6, -12.9)         0.13          0.25             0.52 (0.44, 0.62)
Additional Serotypes
8       96.5             2.9          93.6 (91.2, 95.4)          1.62          0.02          91.19 (81.19, 102.43) 10A       28.9             2.7          26.3 (22.4, 30.3)          0.16          0.02            8.38 (7.20, 9.76) 11A       94.2             2.0          92.2 (89.7, 94.2)          1.62          0.02          74.53 (65.99, 84.17) 12F       30.3             0.2          30.2 (26.5, 34.1)          0.15          0.01          17.91 (15.66, 20.48) 15B       94.3             8.5          85.8 (82.5, 88.5)          3.33          0.04          83.56 (71.77, 97.28) 22F       94.4             2.0          92.4 (89.9, 94.3)          2.25          0.01         337.08 (287.86, 394.72)
33F       46.8             2.7          44.2 (39.8, 48.5)          0.31          0.03          12.19 (10.55, 14.09) 


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Abbreviations: CI = confidence interval; GMC = geometric mean concentration; GMR = geometric mean ratio; IgG = immunoglobulin G; LLOQ = lower limit of quantitation.
Note: Noninferiority for a matched serotype was concluded if the lower bound of the 2-sided 95% CI for the percentage difference (Prevenar 20 – Prevenar 13) was > -10% or the lower bound of the 2-sided 95% CI for the GMR (Pevenar 20 to Prevenar 13) was >0.5 for that serotype.
Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.
a. Study 1012 was conducted in Europe and Australia.
b. The Predefined IgG concentration was ≥0.35 µg/mL for all serotypes except for serotypes 5, 6B and 19A which were ≥0.23 µg/mL, ≥0.10 µg/mL and ≥0.12 µg/mL respectively.
c. N = Number of participants with valid IgG concentrations.
d. Two-sided CI based on the Miettinen and Nurminen method.
e. GMCs, GMRs and the associated 2-sided CIs were calculated by exponentiating the means and the mean differences (Prevenar 20 – Prevenar 13) of the logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution).


OPA responses after 2 and 3 doses in a 3-dose vaccination series of Prevenar 20 The OPA geometric mean titres (GMTs) for the 13 matched serotypes at 1 month after Dose 2 and 1 month after Dose 3 in the Prevenar 20 group were generally similar to the observed OPA GMTs in the Prevenar 13 group for most serotypes. The observed OPA GMTs were lower for serotype 6B after Dose 2 and serotype 1 after Dose 3 in the Pevenar 20 group. OPA GMTs were higher after Dose 3 than after Dose 2 for all serotypes. The observed OPA GMTs for the 7 additional serotypes, including serotypes 10A and 12F, both 1 month after the second dose and 1 month after the third dose were substantially higher in the Prevenar 20 group than those in the Prevenar 13 group (Table 5).
Table 5. Pneumococcal OPA GMTs One Month after Doses 2 and 3 in a 3-dose series, Study 1012a
Prevenar 20              Prevenar 13            Prevenar 20          Prevenar 13 Nb = 96-116                  Nb = 97-118                Nb = 72-106                Nb = 92-109 After Dose 2                After Dose 2               After Dose 3               After Dose 3 GMTc (95% CIc)              GMTc (95% CIc)              GMTc (95% CIc)            GMTc (95% CIc) Serotypes
1          14 (12, 16)                      23 (19, 28)                54 (43, 69)              101 (79, 129) 3          31 (26, 36)                      40 (34, 47)                99 (84, 117)            129 (111, 150) 4         333 (270, 413)                 391 (314, 486)              904 (752, 1086)           992 (777, 1266)
5          21 (18, 23)                      27 (23, 31)                60 (50, 72)               82 (66, 101) 6A         347 (273, 441)                 409 (318, 527)             1101 (897, 1350)          1304 (1018, 1671) 6B          54 (42, 71)                    105 (76, 144)               537 (408, 706)           864 (664, 1125) 7F        858 (736, 1000)                 895 (781, 1027)           1811 (1553, 2112)          2197 (1905, 2533) 9V         233 (182, 298)                 285 (228, 358)            3254 (2596, 4079)          4544 (3681, 5610) 14         287 (215, 383)                 360 (264, 489)               738 (606, 899)           926 (751, 1142) 18C         588 (467, 741)                 719 (590, 876)            1296 (1048, 1602)          1870 (1489, 2348) 19A          57 (43, 75)                     91 (69, 121)               754 (627, 907)           707 (558, 896) 19F          97 (81, 116)                   117 (94, 146)               183 (140, 237)           258 (192, 347) 23F          59 (42, 84)                      68 (48, 96)               697 (530, 917)           975 (734, 1296)
Additional Serotypes
8         164 (133, 203)                    17 (15, 18)            1398 (1088, 1796)              31 (25, 39) 10A        855 (610, 1199)                    39 (34, 44)            3403 (2600, 4455)              69 (52, 91) 11A         327 (253, 423)                    49 (47, 51)            2966 (2212, 3978)              66 (51, 85) 12F       4788 (3779, 6067)                   26 (23, 28)            5501 (4499, 6725)              29 (25, 35) 15B        846 (605, 1183)                    17 (15, 19)            2676 (1948, 3677)              23 (18, 30) 22F       4444 (3666, 5386)                    10 (9, 11)            6523 (4848, 8777)              17 (13, 24)
2373 (1759, 3202)                 178 (163, 195)             11315 (8107,                708 (545, 920
33F                                                                       15794) 2024-0090960
Abbreviations: CI = confidence interval; GMT = geometric mean titre; 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 titres were determined on serum from randomly selected subsets of participants assuring equal representation of both vaccine groups.
a. Study 1012 was conducted in Europe and Australia.
b. N = Number of participants with valid OPA titres.
c. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titres and the corresponding CIs (based on the Student’s t distribution).


Booster responses after the last dose in a 3-dose infant vaccination series Prevenar 20 immune responses show boosting in IgG GMCs and percentage of participants with a predefined IgG concentrations after Dose 3, that are higher than concentrations before Dose 3, and also increased relative to the levels after Dose 2, indicating that a memory response was elicited by the 2 infant doses (see Tables 3 and 4). For all serotypes, the OPA responses also show a generally similar pattern of boosting as observed with the IgG responses, with priming evidenced by the robust OPA responses (geometric mean fold rise (GMFRs) and the percentages of participants with a ≥4-fold rise in OPA titres) from before to one month after Dose 3. In summary, Prevenar 20 elicits immune responses that are comparable to Prevenar 13 for the 13 matched serotypes and the 7 additional serotypes after the third (toddler) dose.

The totality of data show that a 3-dose series of Prevenar 20 elicited immune responses expected to provide children protection against pneumococcal disease similar to that of Prevenar 13 for all 20 vaccine serotypes.
Immune responses following 3 and 4 doses in a 4-dose infant vaccination series Clinical studies evaluating the immunogenicity of Prevenar 20 in infants with a 4-dose series (3 infant doses and a toddler dose) at 2, 4, 6, and 12 to 15 months of age have been conducted in 2 randomised Phase 2 (Study 1003) and Phase 3 studies (Study 1011) in United States/Puerto Rico.
In Study 1011, healthy infants 2 months (≥42 to ≤98 days) of age at the time of consent and born at >36 weeks of gestation, were enrolled. Participants were randomised (1:1) to receive either Prevenar 20 or Prevenar 13 at approximately 2, 4, 6, and 12 to 15 months of age. At one month after the fourth dose, the IgG GMCs for Prevenar 20 were noninferior to Prevenar 13 for all 13 matched serotypes, and 7 additional serotypes to the lowest IgG GMC among the vaccine serotypes (excluding serotype 3) in the Prevenar 13 group based on a 2-fold noninferiority criterion. This was also the case for the IgG GMCs for Prevenar 13, 1 month after the third dose. The percentages of participants with predefined serotype-specific IgG concentrations one month after the third dose was met for 8 of the 13 serotypes and missed by small margins for 4 serotypes (serotypes 1, 4, 9V, and 23F) with a 10% noninferiority criterion. Six of the 7 additional serotypes met the noninferiority criterion; serotype 12F missed the statistical noninferiority criterion. The IgG GMCs at both time points and percentages of participants with predefined IgG concentrations for all 7 additional serotypes, including serotype 12F, were much higher than the corresponding serotype responses in the Prevenar 13 group, consistent with statistically greater antibody levels based on the lower bounds of the nominal 2-sided 95% confidence limits (not adjusted for multiplicity).
OPA GMTs for the 13 matched serotypes 1 month after Dose 3 and Dose 4 in the Prevenar 20 group were generally numerically similar to the OPA GMTs in the Prevenar 13 group, and have similar distributions. The observed OPA GMTs were substantially higher for the 7 additional serotypes in the Prevenar 20 group than the Prevenar 13 group.
Prevenar 20 elicits IgG immune responses that are comparable to Prevenar 13 for the 13 matched serotypes and the 7 additional serotypes after 3 doses in infants and a fourth dose in toddlers. Prevenar 20 also elicits functional antibody to all 20 serotypes that was observed 1 month after Dose 3 and 1 month after Dose 4. Prevenar 20 immune responses also show boosting after Dose 4, indicating that a memory response was elicited by the 3 infant doses.


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Children 15 months to less than 18 years of age (Study 1014)
In a multicenter, single-arm trial (Study 1014), participants were enrolled into the study by age group (approximately 200 participants per group) to receive a single dose Prevenar 20 as described below.
Children 15 months to less than 5 years of age previously vaccinated with Prevenar 13 In 15 to less than 24 months and 2 years to less than 5 years age groups, participants had been previously vaccinated with 3 or 4 doses of Prevenar 13. Increases in IgG concentrations from before to 1 month after Pevenar 20 were observed for all 20 vaccine serotypes in participants 15 months to less than 5 years of age with prior vaccination with Prevenar 13. The observed IgG GMFRs to the 7 additional serotypes ranged from 27.9 to 1847.7 and increases in IgG GMCs were observed in all 20 vaccine serotypes from before to 1 month after Prevenar 20 (Table 6). In children 15 months to less than 24 months of age 83.2% – 100.0% had predefined IgG concentrations to 6 of the 7 additional serotypes, serotype 12F was 40.0%.

Table 6: Pneumococcal IgG GMCs in Participants 15 Months to Less Than 5 Years of Age – Before and 1 Month after Vaccination – Evaluable Immunogenicity Population – Study 1014a
≥15 to <24 Months                                        ≥2 to <5 Years Nb = 186-190                                            Nb = 179-183

Before Vaccination         After Vaccination          Before Vaccination          After Vaccination GMCc (95% CIc)            GMCc (95% CIc)              GMCc (95% CIc)             GMCc (95% CIc) Serotypes
1       0.43 (0.37, 0.49)              1.46 (1.28, 1.67)          0.20 (0.17, 0.24)           4.21 (3.62, 4.90) 3       0.14 (0.12, 0.16)              0.54 (0.47, 0.61)          0.08 (0.06, 0.10)           1.21 (1.04, 1.42) 4       0.61 (0.52, 0.72)              2.59 (2.27, 2.96)          0.30 (0.25, 0.37)           8.37 (7.28, 9.62)
5       0.43 (0.36, 0.50)              1.53 (1.32, 1.77)          0.18 (0.15, 0.22)           5.09 (4.32, 5.99) 6A       1.61 (1.38, 1.88)              7.59 (6.67, 8.63)          0.71 (0.58, 0.88)         31.99 (27.85, 36.75) 6B       0.85 (0.71, 1.02)              4.27 (3.69, 4.94)          0.52 (0.42, 0.63)         17.78 (15.43, 20.48) 7F       1.17 (1.03, 1.33)              3.53 (3.16, 3.94)          0.51 (0.44, 0.60)          6.42 (5.69, 7.24) 9V       0.71 (0.61, 0.83)              2.70 (2.35, 3.09)          0.35 (0.28, 0.42)           7.94 (6.83, 9.24) 14       1.53 (1.31, 1.79)              4.42 (3.82, 5.12)          0.66 (0.53, 0.81)         14.60 (12.44, 17.13) 18C       0.65 (0.55, 0.76)              2.69 (2.32, 3.12)          0.26 (0.21, 0.32)           7.07 (6.01, 8.32) 19A       0.47 (0.38, 0.58)              3.29 (2.89, 3.76)          0.52 (0.40, 0.68)         12.48 (10.76, 14.48) 19F       0.80 (0.67, 0.94)              4.16 (3.61, 4.79)          0.56 (0.44, 0.71)         12.50 (10.48, 14.91) 23F       0.96 (0.79, 1.18)              5.35 (4.55, 6.30)          0.90 (0.71, 1.15)         16.18 (13.75, 19.04)
Additional Serotypes
8       0.04 (0.03, 0.05)              4.66 (4.17, 5.22)          0.05 (0.04, 0.06)           5.08 (4.45, 5.80) 10A       0.01 (0.01, 0.02)              1.23 (1.02, 1.48)          0.03 (0.02, 0.03)           2.76 (2.28, 3.34) 11A       0.03 (0.02, 0.03)              1.61 (1.40, 1.86)          0.06 (0.04, 0.08)           2.64 (2.25, 3.09) 12F       0.01 (0.01, 0.01)              0.22 (0.18, 0.27)          0.01 (0.01, 0.01)           0.38 (0.31, 0.46) 15B       0.02 (0.02, 0.03)              1.17 (0.97, 1.40)          0.05 (0.04, 0.07)           3.96 (3.12, 5.03) 22F       0.01 (0.00, 0.01)             9.57 (8.12, 11.29)          0.02 (0.01, 0.02)         12.46 (10.82, 14.35)
33F       0.02 (0.01, 0.02)              1.91 (1.60, 2.27)          0.04 (0.03, 0.05)           3.16 (2.63, 3.79) Abbreviations: CI = confidence interval; 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.
a. Study 1014 was conducted in the United States.
b. N = Number of participants with valid IgG concentrations at the given sampling time point.
c. GMCs and 2-sided CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student’s t distribution).



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Children and adolescents 5 years to less than 18 years of age previously unvaccinated or vaccinated with Prevenar 13 or Prevenar
In the study, age groups 5 to less than 10 years and 10 to less than 18 years, participants could be unvaccinated or previously vaccinated with Prevenar 13 or Prevenar. Prevenar 20 elicited robust IgG and OPA immune responses to the 20 vaccine serotypes after a single dose in participants 5 to less than 18 years of age. OPA GMFRs ranged from 11.5 to 499.0 to the 7 additional serotypes and increases in OPA GMTs were observed for all 20 vaccine serotypes (Table 7).
In summary, a single dose of Prevenar 20 administered to children and adolescents 15 months to less than 18 years of age is expected to generate protective responses against pneumococcal disease due to the 7 additional serotypes, and to the 13 matched serotypes.

Table 7: Pneumococcal OPA GMTs in Participants 5 to Less Than 18 Years of Age – Before and 1 Month after Vaccination – Evaluable Immunogenicity Population – Study 1014a ≥5 to <10 Years                           ≥10 to <18 Years
Nb=76-175                                                Nb=86-187
Before Vaccination         After Vaccination         Before Vaccination            After Vaccination GMTc (95% CIc)             GMTc (95% CIc)             GMTc (95% CIc)                GMTc (95% CIc) Serotypes
1            10 (9, 11)               548 (455, 660)                11 (9, 12)                 396 (302, 519) 3           29 (22, 40)               155 (135, 178)                19 (14, 24)                 105 (88, 124) 4           43 (27, 67)             2328 (1942, 2789)               34 (22, 51)               2290 (1822, 2878)
5           15 (15, 15)               385 (324, 458)                15 (15, 16)                216 (159, 294) 6A           74 (51, 106)            8268 (6617, 10331)              64 (44, 91)              9434 (7616, 11686) 6B          156 (99, 244)            6569 (5367, 8040)             237 (155, 363)            10085 (8263, 12309) 7F        541 (410, 713)             3981 (3446, 4598)             516 (381, 698)             3326 (2878, 3843) 9V         410 (289, 580)           11717 (9262, 14823)            469 (330, 667)            9627 (7492, 12369) 14        246 (172, 353)             4610 (3688, 5762)              97 (65, 145)              3925 (3153, 4885) 18C         152 (89, 261)             6766 (5585, 8197)              73 (45, 119)              3617 (2816, 4645) 19A         117 (76, 181)             2162 (1786, 2618)              66 (44, 100)              2212 (1801, 2717) 19F          91 (66, 125)              1095 (810, 1479)               57 (44, 73)                551 (401, 757) 23F          87 (53, 145)             2213 (1751, 2797)               46 (29, 73)               1842 (1391, 2439)
Additional Serotypes
8           34 (28, 42)             3870 (3302, 4535)              35 (28, 43)               3125 (2680, 3642) 10A        745 (519, 1071)           21102 (17238, 25833)          554 (395, 777)            17417 (14301, 21214) 11A       1347 (962, 1887)           16882 (13650, 20880)          765 (543, 1076)            11677 (9751, 13982) 12F           48 (38, 60)            23860 (19002, 29959)            46 (36, 59)             20250 (16861, 24320) 15B          79 (54, 115)            25729 (19647, 33695)            45 (33, 61)             21496 (16697, 27672) 22F        259 (170, 394)            33615 (26198, 43130)          243 (161, 366)            27922 (22622, 34463)
33F      3334 (2847, 3905)           45921 (36768, 57353)         2895 (2448, 3424)          32363 (26219, 39946) Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation; OPA = opsonophagocytic activity.
Note: OPA titres for all serotypes were determined on serum from randomly selected subsets of participants except for the 7 additional serotypes among participants ≥5 to <18 years of age, which were determined from all available samples.
Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.
a. Study 1014 was conducted in the United States.
b    n = Number of participants with valid OPA titres at the given sampling time point.
c. GMTs and 2-sided CIs were calculated by exponentiating the mean logarithm of the titres and the corresponding CIs (based on the Student’s t distribution).


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Preterm infants
The safety and tolerability of Prevenar 20 were evaluated in Study 1013, which included 111 late preterm infants (born at 34 to less than 37 weeks of gestational age) among the total study population.
Participants were randomised to receive a 4-dose series of either Prevenar 20 (N=77) or Prevenar 13 (N=34). Studies have not been specifically conducted to describe the immunogenicity of Prevenar 20 in preterm infants. Based on experience with Prevenar and Prevenar 13, immune responses are elicited in preterm infants, although they may be lower than in term infants.


Prevenar 20 clinical trials in adults
Three Phase 3 clinical trials, B7471006, B7471007 and B7471008 (Study 1006, Study 1007, and Study 1008), were conducted in the United States and Sweden evaluating the immunogenicity of Prevenar 20 in different adult age groups, and in participants who were either pneumococcal vaccine-naïve, or previously vaccinated with Prevenar 13, PPSV23, or both.

Each study included participants who were healthy or immunocompetent with stable underlying conditions, including chronic cardiovascular disease, chronic pulmonary disease, renal disorders, diabetes mellitus, chronic liver disease, and medical risk conditions and behaviours (e.g., smoking) that are known to increase the risk of serious pneumococcal pneumonia and IPD. In the pivotal study (Study 1007), these risk factors were identified in 34%, 32%, and 26% of participants 60 years of age and over, 50 to 59 years of age, and 18 to 49 years of age, respectively. A stable medical condition was defined as a medical condition not requiring significant change in therapy in the previous 6 weeks (i.e., change to new therapy category due to worsening disease), or any hospitalization for worsening disease within 12 weeks before receiving the study vaccine.

In each study, immune responses elicited by Prevenar 20 and the control pneumococcal vaccines were measured by an opsonophagocytic activity (OPA) assay. OPA assays measure functional antibodies to S. pneumoniae.

Comparison of immune responses of Prevenar 20 to Prevenar 13 and PPSV23 
In a randomised, active-controlled, double-blind, non-inferiority clinical trial (Pivotal Study 1007) of Prevenar 20 in the United States and Sweden, pneumococcal vaccine-naïve participants 18 years of age and older were enrolled into 1 of 3 cohorts based on their age at enrollment (18 to 49, 50 to 59, and ≥ 60 years of age), and randomised to receive Prevenar 20 or control. Participants 60 years of age and older were randomised in a 1:1 ratio to receive Prevenar 20 (n = 1,507) followed 1 month later with the administration of saline placebo or Prevenar 13 (n = 1,490), and with the administration of PPSV23 1 month later. Participants 18 to 49 years of age and 50 to 59 years of age were randomly assigned (3:1 ratio); they received a dose of Prevenar 20 (18 to 49 years of age: n = 335; 50 to 59 years of age: n = 334) or Prevenar 13 (18 to 49 years of age: n = 112; 50 to 59 years of age: n = 111).

Serotype-specific OPA GMTs were measured before the first vaccination and 1 month after each vaccination. Non-inferiority of immune responses, OPA GMTs 1 month after vaccination, with Prevenar 20 to a control vaccine for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMT ratio (Prevenar 20/Prevenar 13; Prevenar 20/PPSV23) for that serotype was greater than 0.5.

In participants 60 years of age and older, the immune responses to all 13 matched serotypes elicited by Prevenar 20 were non-inferior to those elicited by Prevenar 13 for the same serotypes 1 month after vaccination. In general, numerically lower geometric mean titres were observed with Prevenar 20 in the matched serotypes compared to Prevenar 13 (Table 8), however the clinical relevance of these findings is unknown.

The immune responses induced by Prevenar 20 to 6/7 additional serotypes were non-inferior to those induced by PPSV23 to the same serotypes 1 month after vaccination. The response to serotype 8 2024-0090960
missed the pre-specified statistical non-inferiority criterion (the lower bound of the 2-sided 95% CI for the GMT ratio is 0.49 instead of > 0.50) (Table 8). The clinical relevance of this observation is unknown. Supportive analyses for other serotype 8 endpoints in the Prevenar 20 group showed favourable outcomes. These include a GMFR of 22.1 from before vaccination to 1 month post- vaccination, 77.8% of participants achieved a ≥ 4-fold rise in OPA titres from before vaccination to 1 month after vaccination, and 92.9% of participants achieved OPA titres ≥ LLOQ 1 month after vaccination.

Table 8.      OPA GMTs 1 Month After Vaccination in Participants 60 Years of Age and Older Given Prevenar 20 Compared to Prevenar 13 for the 13 Matched Serotypes and to PPSV23 for the 7 Additional Serotypes (Study 1007)a,b,c,d
Prevenar 13       PPSV23
Prevenar 20          (N = 1390–      (N = 1201–       Vaccine Comparison (N = 1157–1430)           1419)          1319)
GMT Ratioe   95% CIe e                    e              e
GMT                  GMT            GMT
Serotype
1                     123                           154                                    0.80          0.71, 0.90 3                      41                            48                                    0.85          0.78, 0.93 4                     509                           627                                    0.81          0.71, 0.93
5                      92                           110                                    0.83          0.74, 0.94 6A                    889                           1165                                   0.76          0.66, 0.88 6B                   1115                           1341                                   0.83          0.73, 0.95 7F                    969                           1129                                   0.86          0.77, 0.96 9V                   1456                           1568                                   0.93          0.82, 1.05 14                    747                           747                                    1.00          0.89, 1.13 18C                  1253                           1482                                   0.85          0.74, 0.97 19A                   518                            645                                   0.80          0.71, 0.90 19F                   266                           333                                    0.80          0.70, 0.91 23F                   277                           335                                    0.83          0.70, 0.97
Additional Serotypes
8                     466                                               848                0.55          0.49, 0.62 10A                  2008                                              1080                1.86          1.63, 2.12 11A                  4427                                              2535                1.75          1.52, 2.01 12F                  2539                                              1717                1.48          1.27, 1.72 15B                  2398                                               769                3.12          2.62, 3.71 22F                  3666                                              1846                1.99          1.70, 2.32
33F                  5126                                              3721                1.38          1.21, 1.57 Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation; N = number of participants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine (23-valent).
a. Study 1007 was conducted in the United States and in Sweden.
b. Non-inferiority for a serotype was met if the lower bound of the 2-sided 95% CI for the GMT ratio (ratio of Prevenar 20/comparator) was greater than 0.5 (2-fold criterion for non-inferiority).
c. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.
d. Evaluable immunogenicity population.
e. GMTs and GMT ratios as well as the associated 2-sided CIs were based on analysis of log-transformed OPA titres using a regression model with vaccine group, sex, smoking status, age at vaccination in years, and baseline log transformed OPA titres.

Immunogenicity in participants 18 through 59 years of age

In Study 1007, participants 50 through 59 years of age and participants 18 through 49 years of age were randomly assigned (3:1 ratio) to receive 1 vaccination with Prevenar 20 or Prevenar 13.
Serotype-specific OPA GMTs were measured before vaccination and 1 month after vaccination. With both vaccines, higher immune responses were observed in younger participants compared with older participants. A non-inferiority analysis of Prevenar 20 in the younger age group versus Prevenar 20 in participants 60 through 64 years of age per serotype was performed to support the indication in adults 2024-0090960
18 through 49 years of age and 50 through 59 years of age. Non-inferiority was declared if the lower bound of the 2-sided 95% CI for the GMT ratio (Prevenar 20 in participants 18 through 49 years of age / 60 through 64 years of age and in 50 through 59 years of age / 60 through 64 years of age) for each of the 20 serotypes was > 0.5. Prevenar 20 elicited immune responses to all 20 vaccine serotypes in the two of the younger age groups that were non-inferior to responses in participants 60 through 64 years of age 1 month after vaccination (Table 9).

While not planned as an active control for immunogenicity evaluations in the study, a post hoc descriptive analysis showed generally numerically lower OPA GMTs 1 month after Prevenar 20 for the matched serotypes compared to Prevenar 13 in participants 18 through 59 years of age, however the clinical relevance of these findings is unknown.

As noted above, individuals with risk factors were included in this study. Across all the age groups studied, in general, a numerically lower immune response was observed in participants with risk factors compared to participants without risk factors. The clinical relevance of this observation is unknown.

Table9.    Comparisons of OPA GMTs 1 Month After Prevenar 20 in Participants 18 Through 49 or 50 Through 59 Years of Age to Participants 60 Through 64 Years of Age
(Study 1007)a,b,c,d
18–49 Years                  60–64 Years 50–59 Years
18–49 Years 60–64 Years       Relative to 50–59 Years       (N = 765–    Relative to (N = 251–317) (N = 765–941) 60–64 Years (N = 266–320)           941)     60–64 Years GMT Ratioe                                 GMT Ratioe e               e               e           e              e
GMT             GMT         (95% CI)        GMT            GMT         (95% CI)e Serotype
1.23                                       1.03
1           163             132      (1.01, 1.50)       136           132       (0.84, 1.26) 1.00                                       1.06
3            42              42      (0.87, 1.16)        43            41       (0.92, 1.22) 3.31                                       1.10
4          1967             594      (2.65, 4.13)       633           578       (0.87, 1.38)
1.11                                       0.88
5           108              97      (0.91, 1.36)        85            97       (0.72, 1.07) 3.84                                       1.21
6A         3931            1023      (3.06, 4.83)      1204           997       (0.95, 1.53) 3.41                                       1.25
6B         4260            1250      (2.73, 4.26)      1503          1199       (1.00, 1.56) 1.58                                       0.89
7F         1873            1187      (1.30, 1.91)      1047          1173       (0.74, 1.07) 3.50                                       1.02
9V         6041            1727      (2.83, 4.33)      1726          1688       (0.83, 1.26) 2.39                                       1.25
14         1848             773      (1.93, 2.96)       926           742       (1.01, 1.54) 3.20                                       1.33
18C        4460            1395      (2.53, 4.04)      1805          1355       (1.06, 1.68) 2.31                                       1.03
19A        1415             611      (1.91, 2.81)       618           600       (0.85, 1.25) 2.17                                       0.99
19F         655             301      (1.76, 2.68)       287           290       (0.80, 1.22) 4.80                                       1.68
23F        1559             325      (3.65, 6.32)       549           328       (1.27, 2.22)
Additional Serotypes
1.71                                       0.97
8           867             508      (1.38, 2.12)       487           502       (0.78, 1.20) 
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Table9.      Comparisons of OPA GMTs 1 Month After Prevenar 20 in Participants 18 Through 49 or 50 Through 59 Years of Age to Participants 60 Through 64 Years of Age
(Study 1007)a,b,c,d
18–49 Years                  60–64 Years 50–59 Years
18–49 Years 60–64 Years       Relative to 50–59 Years       (N = 765–    Relative to (N = 251–317) (N = 765–941) 60–64 Years (N = 266–320)           941)     60–64 Years GMT Ratioe                                 GMT Ratioe
GMTe            GMTe        (95% CI)e       GMTe           GMTe        (95% CI)e 1.62                                       1.03
10A         4157             2570      (1.31, 2.00)      2520          2437       (0.84, 1.28) 1.32                                       1.22
11A         7169             5420      (1.04, 1.68)      6417          5249       (0.96, 1.56) 1.91                                       1.11
12F         5875             3075      (1.51, 2.41)      3445          3105       (0.88, 1.39) 1.52                                       1.17
15B         4601             3019      (1.13, 2.05)      3356          2874       (0.88, 1.56) 1.69                                       0.90
22F         7568             4482      (1.30, 2.20)      3808          4228       (0.69, 1.17)
1.40                                       1.02
33F         7977             5693      (1.10, 1.79)      5571          5445       (0.81, 1.30) Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation; N = number of participants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine (23-valent).
a. Study 1007 was conducted in the United States and in Sweden.
b. Non-inferiority for a serotype was met if the lower bound of the 2-sided 95% CI for the GMT ratio (ratio of younger age group/60 through 64 years of age group) was greater than 0.5 (2-fold criterion for non-inferiority).
c. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.
d. Evaluable immunogenicity population.
e. GMTs, GMT ratios, and the associated 2-sided CIs were based on analysis of log-transformed OPA titres using a regression model with age group, sex, smoking status, and baseline log transformed OPA titres. The comparisons between participants 18 through 49 years of age and participants 60 through 64 years of age and between participants 50 through 59 years of age and participants 60 through 64 years of age were based on separate regression models.

Immunogenicity of Prevenar 20 in adults previously vaccinated with pneumococcal vaccine 
A Phase 3 randomised, open-label clinical trial (Study 1006) described immune responses to Prevenar 20 in participants 65 years of age and older previously vaccinated with PPSV23, with Prevenar 13, or with Prevenar 13 followed by PPSV23. Participants previously vaccinated with Prevenar 13 (Prevenar 13 only or followed by PPSV23) were enrolled at sites in the United States, whereas participants and previously vaccinated with PPSV23 only were also enrolled from Swedish sites (35.5% in that category).

Prevenar 20 elicited immune responses to all 20 vaccine serotypes in participants 65 years of age and older with prior pneumococcal vaccination (Table 10). Immune responses were lower in participants in both groups who received prior PPSV23 vaccinations.

Table 10. Pneumococcal OPA GMTs Before and 1 Month After Prevenar 20 in Participants 65 Years of Age and Older With Prior Pneumococcal Vaccination (Study 1006)a,b,c,d Prior Prevenar 13 and
Prior PPSV23 only         Prior Prevenar 13 only             PPSV23
Before          After        Before         After        Before         After vaccination     vaccination  vaccination vaccination     vaccination vaccination (N = 208–247) (N = 216–246) (N = 210-243) (N = 201–243) (N = 106–121) (N = 102-121) GMT             GMT          GMT            GMT          GMT            GMT (95% CI)e       (95% CI)e    (95% CI)e     (95% CI)e     (95% CI)e     (95% CI)e Serotype
24             51            34            115           42            82
1        (20, 28)        (42, 62)     (28, 41)      (96, 138)     (32, 56)      (61, 110) 
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Table 10. Pneumococcal OPA GMTs Before and 1 Month After Prevenar 20 in Participants 65 Years of Age and Older With Prior Pneumococcal Vaccination (Study 1006)a,b,c,d Prior Prevenar 13 and
Prior PPSV23 only          Prior Prevenar 13 only             PPSV23
Before          After         Before          After       Before         After vaccination       vaccination  vaccination vaccination     vaccination vaccination (N = 208–247) (N = 216–246) (N = 210-243) (N = 201–243) (N = 106–121) (N = 102-121) GMT             GMT           GMT             GMT         GMT            GMT (95% CI)e        (95% CI)e    (95% CI)e       (95% CI)e   (95% CI)e      (95% CI)e 13              31           15              54           20            39 3          (11, 15)        (27, 36)      (13, 18)        (47, 63)    (17, 25)       (32, 48) 29             150           67             335           73           194
4          (23, 35)       (118, 190)     (53, 84)      (274, 410)   (53, 101)     (143, 262)
27              63           38              87           47            83
5          (24, 31)        (53, 75)      (32, 44)       (73, 104)    (37, 59)      (65, 108) 57             749          125            1081          161          1085 6A         (46, 70)       (577, 972)    (99, 158)     (880, 1327)  (116, 224)    (797, 1478) 107             727          174            1159          259          1033 6B        (86, 133)       (574, 922)   (138, 219)     (951, 1414)  (191, 352)    (755, 1415) 156             378          210             555         206            346 7F       (132, 184)       (316, 452)   (175, 251)      (467, 661)  (164, 258)     (277, 432) 203             550          339            1085          352           723
9V       (171, 241)       (454, 667)   (282, 408)     (893, 1318)  (270, 459)     (558, 938) 212             391          282             665         336            581
14       (166, 270)       (315, 486)   (224, 356)      (554, 798)  (238, 473)     (434, 777) 173             552          219             846         278            621 18C      (137, 218)       (445, 684)   (177, 272)     (693, 1033)  (209, 369)     (470, 821) 82             239          124             365         182            341 19A       (66, 100)       (197, 288)   (100, 153)      (303, 440)  (141, 235)     (264, 439) 61             159           89             242          120           218 19F        (52, 71)       (131, 192)    (74, 107)      (199, 294)   (94, 154)     (168, 282) 23             152           48             450           66           293
23F        (18, 28)       (115, 199)     (37, 62)      (358, 566)    (46, 94)     (204, 420)
Additional Serotypes
55             212           28             603          139           294 8          (45, 67)       (172, 261)     (24, 33)      (483, 753)   (99, 195)     (220, 392) 212            1012          141            2005          400          1580
10A      (166, 269)      (807, 1270)   (113, 177)    (1586, 2536)  (281, 568)   (1176, 2124) 510            1473          269            1908          550          1567 11A      (396, 656)     (1192, 1820)   (211, 343)    (1541, 2362)  (386, 785)   (1141, 2151) 147            1054           53            1763          368          1401 12F      (112, 193)      (822, 1353)     (43, 65)    (1372, 2267)  (236, 573)   (1002, 1960) 140             647           74            1480          190          1067 15B      (104, 189)       (491, 853)     (56, 98)    (1093, 2003)  (124, 291)    (721, 1578) 167            1773           60            4157         286           2718 22F      (122, 230)     (1355, 2320)     (45, 82)    (3244, 5326)  (180, 456)   (1978, 3733)
1129            2026          606            3175         1353          2183 33F     (936, 1362)     (1684, 2437)   (507, 723)    (2579, 3908) (1037, 1765) (1639, 2908) Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation; N = number of participants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine (23-valent).
a. Study 1006 was conducted in the United States and in Sweden.
b. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.
c. Evaluable immunogenicity population.
d. Open-label administration of Prevenar 20.
e. 2-sided CIs based on the Student t distribution.


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Concomitant vaccine administration

Paediatric population
In Study 1012, the concomitant administration of Infanrix hexa (containing DTaP, HBV, IPV, and Hib antigens) with all 3 doses of Prevenar 20 or Prevenar 13 and single doses of a vaccine containing MMR antigens and Varilrix (varicella antigens) were also administered with the third dose and evaluated 1 month after the third (toddler) dose of Prevenar 20 or Prevenar 13.
Noninferiority was demonstrated for immune responses to diphtheria, tetanus, acellular pertussis, hepatitis B, poliovirus, Hib, MMR, and varicella vaccine antigens co-administered with Prevenar 20 compared with Prevenar 13. The results from Study 1012 support co- administration of Prevenar 20 with routine paediatric vaccines. No safety concerns were identified in this study.

In Study 1011, the concomitant administration of a vaccine containing DTaP, HBV, IPV antigens and Hiberix (Hib antigen) with each of the 3 infant doses of either Pevenar 20 or Prevenar 13 were evaluated 1 month after the third dose. Concomitant administration of single doses of M-M-R II (MMR antigens) and Varivax (varicella antigens) with the fourth dose of either Prevenar 20 or Prevenar 13 were evaluated 1 month following vaccination.
Noninferiority was demonstrated for immune responses to the co-administered diphtheria, tetanus, acellular pertussis, hepatitis B virus, poliovirus, and Hib vaccine antigens 1 month after 3 infant doses and coadministered MMR, and varicella virus vaccine antigens after the fourth (toddler) dose of Prevenar 20 compared with Prevenar 13. The results from Study 1011 support co-administration of Prevenar 20 with routine paediatric vaccines. No safety concerns were identified in this study.

Influenza and rotavirus vaccines were permitted to be administered concomitantly at any time during these studies according to local or national recommendations.


Immune responses in special populations
Individuals with the conditions described below have an increased risk of pneumococcal disease.

Studies in individuals with SCD, HIV, and HSCT have not been conducted with Prevenar 20.

Experience from clinical studies with Prevenar 13 (a pneumococcal conjugate vaccine consisting of 13 polysaccharide conjugates that are also in Prevenar 20) are available in children and adults at higher risk of pneumococcal infection including immunocompromised children and adults with HIV infection or HSCT, and children with SCD.

Participants who were healthy, or with stable non-immunocompromising chronic medical conditions, in all the age groups analysed had a lower immune response with Prevenar 20 compared with Prevenar 13 in spite of meeting the predefined non-inferiority margins. The clinical relevance of this observation is unknown.

Sickle cell disease (SCD)

An open-label single-arm study with 2 doses of Prevenar 13 given 6 months apart was conducted in 158 children and adolescents 6 to < 18 years of age with SCD who were previously vaccinated with one or more doses of 23-valent pneumococcal polysaccharide vaccine at least 6 months prior to enrollment. After the first vaccination, Prevenar 13 elicited antibody levels measured by both IgG GMCs and OPA GMTs that were statistically significantly higher when compared with levels prior to vaccination. After the second dose, immune responses were comparable to those after the first dose.
One year after the second dose, antibody levels measured by both IgG GMCs and OPA GMTs were 2024-0090960
higher than levels prior to the first dose of Prevenar 13, except for the IgG GMCs for serotypes 3 and 5 that were numerically similar.

HIV infection

Children and adults not previously vaccinated with a pneumococcal vaccine In Study 6115A1-3002 (B1851021), 151 participants 6 to < 18 years of age and 152 participants ≥ 18 years of age infected with HIV (CD4 ≥ 200 cells/µL, viral load < 50,000 copies/mL and free of active acquired immunodeficiency syndrome [AIDS]-related illness) not previously vaccinated with a pneumococcal vaccine were enrolled to receive 3 doses of Prevenar 13. As per the general recommendations, a single dose of PPSV23 was subsequently administered. The vaccines were administered at 1-month intervals. Immune responses were assessed in 128 to 133 evaluable participants 6 to < 18 years of age and in 131 to 137 evaluable participants ≥ 18 years of age approximately 1 month after each dose of the vaccine. After the first dose, Prevenar 13 elicited antibody levels, measured by IgG GMCs and OPA GMTs, that were statistically significantly higher compared with levels prior to vaccination. After the second and third dose of Prevenar 13, immune responses were similar to or higher than those after the first dose.

Adults previously vaccinated with PPSV23
In Study 6115A1-3017 (B1851028), immune responses were assessed in 329 HIV-infected participants ≥18 years of age (CD4+ T-cell count ≥ 200 cells/µL and viral load < 50,000 copies/mL) previously vaccinated with PPSV23 administered at least 6 months prior to enrolment. Participants received 3 doses of Prevenar 13: at enrolment, 6 months, and 12 months after the first dose of Prevenar 13. After the first vaccination, Prevenar 13 elicited antibody levels measured by IgG GMCs and OPA GMTs that were statistically significantly higher compared with levels prior to vaccination.
After the second and third dose of Prevenar 13, immune responses were comparable to or higher than those after the first dose. Participants who received previously 2 or more doses of PPSV23 showed a similar immune response compared to participants who previously received a single dose.

Haematopoietic stem cell transplant (HSCT)

In Study 6115A1-3003 (B1851022), 61 participants 2 to < 18 years of age and 190 participants ≥18 years of age with an allogeneic HSCT were enrolled to receive 3 doses of Prevenar 13 with an interval of at least 1 month between doses. The first dose was administered at 3 to 6 months after HSCT. A fourth (booster) dose of Prevenar 13 was administered 6 months after the third dose. As per the general recommendations, a single dose of PPSV23 was administered 1 month after the fourth dose of Prevenar 13. Immune responses as measured by IgG GMCs, were assessed in 41 to 52 evaluable participants 2 to < 18 years of age and in 127 to 159 evaluable participants ≥ 18 years of age approximately 1 month after vaccination. Prevenar 13 elicited increased antibody levels after each dose. Immune responses after the fourth dose of Prevenar 13 were significantly increased for all serotypes compared with those after the third dose with the exception of serotype 3 in the 2 to < 18 years age group. Overall, participants 2 to < 18 years of age had generally higher serotype specific immune responses compared with those ≥ 18 years of age.

This study demonstrated that 4 doses of Prevenar 13 elicited serum IgG concentrations similar to those induced by a single dose in healthy participants of the same age group.


Invasive pneumococcal disease (IPD)
Vaccine effectiveness of Prevenar 13 against vaccine-serotype IPD was evaluated in the SpIDnet study, a multi-country enhanced IPD surveillance project in Europe. Based on data over a 6-year period (2012-2018) from 10 sites in 7 European countries using Prevenar 13, the effectiveness against IPD caused by serotypes in the vaccine among children < 5 years of age was 84.2% (95% CI, 

2024-0090960
79.0-88.1) and 88.7% (95% CI, 81.7-92.7) in children receiving ≥ 1 Prevenar 13 dose and a complete vaccination schedule, respectively.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Not applicable.