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Clinical Trials: PCV13-TT Immunogenicity Clinical Trials in Healthy Subjects 2 through 71 Months of Age: In China, the pivotal phase III clinical trial of PCV13-TT was a randomized, blind and non-inferiority study comparing to Prevenar. This study evaluated the immunogenicity and safety of PCV13-TT and Prevenar in 2760 healthy subjects 2 through 71 months of age (at least 6 weeks of age). A total of 1040 infants aged 3 months were randomized in a 1:1 ratio as the PCV13-TT group and the Prevenar group, with PCV13-TT or Prevenar given at 3, 4, 5, and 12-15 months of age, respectively; for 520 infants aged 2 months (at least 6 weeks of age), PCV13-TT was vaccinated at 2, 4, 6 and 12-15 months of age. 1200 children of 7 through 71 months of age, including children 7 months through 11 months of age, 12 months through 23 months of age and 24 months through 5 years of age (prior to the 6th birthday) who were naïve to the pneumococcal conjugate vaccine, were split into three age groups with each containing 400 subjects randomized in a 1:1 ratio given 3, 2 or 1 dose of PCV13-TT or Prevenar, respectively, according to the age-appropriate schedules in Table 8 to Table 10.
Immune responses elicited by PCV13-TT and Prevenar were measured by serotype-specific IgG antibody concentration and the geometric mean concentration (GMC) of serotype-specific IgG antibody one month post primary series as primary endpoints. The IgG and GMC of IgG post booster dose, as well as serotype-specific OPA titer and OPA geometric mean titer (GMT) one month post primary series and booster dose as secondary endpoints.
For the 7 serotypes in common to both vaccines, non-inferiority between vaccines was met if the lower limit of the 2-sided 97.5% confidence interval (CI) of the positive rate difference (PCV13-TT minus the Prevenar) was not less than -10%, or the lower limit of 2-sided 97.5% CI of the GMC ratio (PCV13-TT/Prevenar) was not less than 0.5.
The response to the 6 additional serotypes, which is contained in PCV13-TT but not in Prevenar, superiority between vaccines was met if the lower limit of 2-sided 95% CI of antibody positive rate was not less than 0, the lower limit of 2-sided 95% CI of the GMC ratio (PCV13-TT/Prevenar) was not less than 1, and the lower limit of 2-sided 95% CI of IgG antibody positive rate was not less than 70%.
A subset of sera randomly obtained from 100 subjects in each age group for PCV13-TT and Prevenar, totaling 900 subjects were tested by opsonophagocytic assay (OPA) to measure the ability of serotype-specific functional antibodies to eliminate corresponding pneumococci by promoting complement-mediated phagocytosis.
For immunogenicity assessment, the immunogenicity results of PCV13-TT (2 months of age) group, Prevenar (3 months of age) group and PCV13-TT (3 months of age) group were compared in sequence (please refer to Table 8 and Table 9 for dosing regimen for subjects in PCV13-TT (2 months of age) group and Prevenar (3 months of age group). The results are shown as follows: Main target population (3 months of age): Primary series: In PCV13-TT (3 months of age) group, after primary series, six out of seven common serotypes met the non-inferiority criteria with the exception of 6B; the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT group were non-inferior to the serotype with the lowest response among all the 7 common serotypes in the Prevenar group.
Booster dose: In PCV13-TT (3 months of age) group, after complete series, all 7 common serotypes met the non-inferiority criteria; the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT group were non-inferior to the serotype with the lowest response among all the 7 common serotypes in the Prevenar group.
For PCV13-TT (2 months of age) group vs Prevenar (3 months of age) group: Primary series: In PCV13-TT (2 months of age) group, after primary series, the IgG antibody was firstly compared between the PCV13-TT (2 months of age) group and the Prevenar (3 months of age) group, showing that all 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT (2 months of age) group were non-inferior to the serotype with the lowest IgG response among all 7 common serotypes in the Prevenar (3 months of age) group. The IgG antibody was then compared between the PCV13-TT (2 months of age) group and the PCV13-TT (3 months of age) group. IgG antibody of twelve out of the thirteen serotypes met the non-inferiority criteria with the exception of serotype 5.
Booster dose: In PCV13-TT (2 months of age) group, after complete series, the IgG antibody was firstly compared between the PCV13-TT (2 months of age) group and the Prevenar (3 months of age) group. All 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT (2 months of age) group were non-inferior to the serotype with the lowest IgG response among all 7 common serotypes in the Prevenar (3 months of age) group. The IgG antibody was then compared between the PCV13-TT (2 months of age) group and the PCV13-TT (3 months of age) group. IgG antibody of all the 13 serotypes met the non-inferiority criteria.
For PCV13-TT (7-11 months of age) group: Primary series: In PCV13-TT (7-11 months) group, after primary series, the proportions of subjects with IgG antibody concentration ≥0.35 μg/mL for common serotypes were all non-inferior to those in Prevenar group. The additional serotypes in PCV13-TT (7-11 months of age) group had reached superiority criteria after primary series.
Booster dose: In PCV13-TT (7-11 months of age) group, after complete series, all 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes (except 19A) reached superiority threshold.
For PCV13-TT (12-23 months of age) group and PCV13-TT (24-71 months) group: Complete series: The proportions of subjects with IgG antibody concentration ≥0.35 μg/mL for common serotypes were all non-inferior to those in Prevenar group. The additional serotypes in PCV13-TT (12-23 months) group and PCV13-TT (24-71 months of age) group, superiority criteria were generally met after primary series, except for serotype 19A in PCV13-TT (12-23 months of age) group and serotypes 6A and 19A in PCV13-TT (24-71 months of age) group.
Please refer to Table 10 for dosing regimen for subjects in PCV13-TT (7-11 months of age) group, PCV13-TT (12-23 months of age) group and PCV13-TT (24-71 months of age) group.
The testing results of OPA antibody demonstrated that all 13 serotypes of PCV13-TT were capable of inducing anti-pneumococcal OPA antibodies in all age groups in the PCV13-TT group.
The immunogenicity data from subjects 2 months (at least 6 weeks of age) through 71 months of age are shown in Table 2 to Table 7. (See Tables 2 to 7.)
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