Vaccine Information: Adacel TDaP (Page 4 of 6)

14.2 Immunological Evaluation in Adults, 18 through 64 Years of Age Following a Second Vaccination with Adacel

In study Td537 [See ADVERSE REACTIONS (6.1).], subjects 18 to 64 years of age who had received a dose of Adacel 8-12 years previously, were randomized to receive a second dose of Adacel or Td vaccine (Tetanus and Diphtheria Toxoids Adsorbed manufactured by Sanofi Pasteur, Limited). Blood samples for immunogenicity analyses were obtained from participants pre-vaccination and approximately 28 days post-vaccination. The per-protocol analysis set was used for all immunogenicity analyses, and included 948 participants in the Adacel group and 317 participants in the Td control vaccine group. Of the study participants, 35% were male. Of subjects who reported a racial/ethnic demographic, 95% were Caucasian, 2% Black, 0.5% American Indian or Alaska native, 1% Asian and 1.5% were of mixed or other origin.

A tetanus antitoxoid level of ≥ 0.1 IU/mL, measured by the ELISA used in this study was considered protective. An anti-diphtheria anti-toxin level of ≥ 0.1 IU/mL was considered protective. Pre-vaccination and post-vaccination seroprotection rates and booster response rates are presented in Table 8.

Table 8: Pre-vaccination and Post-vaccination Seroprotection Rates and Booster Response Rates to Tetanus Toxoid and Diphtheria Toxoid Following a Second Vaccination with Adacel Compared to Td Vaccine in Persons 18 through 64 Years of Age, Per Protocol Analysis Set
Vaccine N * Pre-vaccination 1 month post-vaccination
≥0.1 IU/mL(95% CI) ≥1.0 IU/mL(95% CI) ≥0.1 IU/mL(95% CI) ≥1.0 IU/mL (95% CI) %Booster §(95% CI)
*
N = number of participants in the per-protocol population with available data.
Seroprotection rates at ≥0.10 IU/mL for Adacel were non-inferior to Td for diphtheria toxin and tetanus toxoid (upper limit of the 95% CI on the difference for Td vaccine minus Adacel <10%).
Seroprotection rates at ≥1.0 IU/mL were not prospectively defined as a primary or secondary endpoint.
§
Booster response is defined as a minimum rise in antibody concentration from pre to post-vaccination. The minimum rise is at least 2 times if the pre-vaccination concentration is above the cutoff value, or at least 4 times if it is at or below the cutoff value. The cutoff values for to tetanus and diphtheria are 2.7 IU/mL and 2.56 IU/mL, respectively.
n/M: defines the number n of participants with booster response / the number M of subjects with available data to evaluate booster response. There were (n/M) 703/944, 257/315, 786/945 and 265/315 for Adacel/Tetanus, Td Adsorbed/Tetanus, Adacel/Diphtheria, and Td Adsorbed/Diphtheria, respectively.
#
Booster response rates for tetanus toxoid in Adacel did not meet the pre-specified non-inferiority criteria.
Þ
Tetanus and Diphtheria Toxoids Adsorbed manufactured by Sanofi Pasteur Limited, Toronto, Ontario, Canada.
Anti- Tetanus Toxoid (ELISA — IU/mL) Adacel 944-948 97.2(96.0; 98.2) 62.3(59.1; 65.4) 100.0(99.6; 100.0) 99.9(99.4; 100.0) 74.5#(71.6; 77.2)
Td Þ Adsorbed 315-317 96.5(93.8; 98.2) 63.8(58.2; 69.1) 100.0(98.8; 100.0) 100.0(98.8; 100.0) 81.6#(76.9; 85.7)
Anti- Diphtheria Toxin (ELISA — IU/mL) Adacel 945-948 84.7(82.2; 86.9) 29.1(26.2; 32.1) 99.8(99.2; 100.0) 94.9(93.3; 96.2) 83.2(80.6; 85.5)
Td Þ Adsorbed 315-317 83.8(79.3; 87.7) 29.8(24.8; 35.2) 99.4(97.7; 99.9) 94.0(90.8; 96.4) 84.1(79.6; 88.0)

For all pertussis antigens (PT, FHA, PRN and FIM), post-vaccination anti-pertussis GMCs in the Adacel group were non-inferior to GMCs induced by 3 or 4 doses of DAPTACEL in historical studies as are presented in Table 9.

Table 9: Ratio of Pertussis Antibody Geometric Mean Concentrations (GMCs) Observed One Month Following a Second Vaccination with Adacel in Adults Compared with Those Observed in Infants One Month following Vaccination with 3 or 4 Doses of DAPTACEL (Per-Protocol Analysis Set)
Antigen Adacel DAPTACEL * Adacel/DAPTACEL *
N GMC(EU/mL) (95% CI) N GMC(EU/mL) (95% CI) GMC Ratio (95% CI)
*
DAPTACEL: Historical controls who received DAPTACEL in Sanofi Pasteur studies. PT antibody GMC were compared to GMC following 4 doses of DAPTACEL in M5A10. FHA, PRN and FIM antibody GMCs were compared to GMCs following 3 doses of Daptacel in the Sweden I Efficacy trial.
For each pertussis antigen, non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMC ratio (Adacel divided by the historical control) was > 0.66.
PT 935 102 (94.9; 110) 366 98.1 (90.9; 106) 1.04 (0.92; 1.18)
FHA 948 209 (200; 217) 80 39.9 (34.6; 46.1) 5.22 (4.51; 6.05)
PRN 948 318 (302; 334) 80 108 (91.4; 128) 2.94 (2.46; 3.51)
FIM 948 745 (711; 781) 80 341 (270; 431) 2.18 (1.84; 2.60)

Booster response rates for PT and FHA were non-inferior in Adacel participants compared to pre-specified criteria for booster response rates, but non-inferiority was not achieved for PRN and FIM booster response rates (See Table 10).

Table 10: Comparison of Booster Response * Rates for Pertussis Antigens Following a Second Vaccination with Adacel (Per-Protocol Analysis Set)
Adacel (N=948) Pre-specified criteria for Booster Response Rates Adacel minus Pre-specified Booster Response Rates
Antigen n/M % (95% CI) % Difference (%) (95% CI)
N= number of subjects analyzed according to Per-Protocol Analysis SetM=number of subjects with available data for the considered endpointn= number of subjects fulfilling the item listed in the first column
*
Booster response is defined as a minimum rise in antibody concentration from pre to post-vaccination. The minimum rise is at least 2-fold if the pre-vaccination concentration is above the cutoff value, or at least 4-fold if it is at or below the cutoff value. The cutoff values for Study Td537 for the pertussis antigens are: 93 EU/mL for PT, 170 EU/mL for FHA, 115 EU/mL for PRN, and 285 EU/mL for FIM.
Pre-specified criteria for booster response rates were derived from participants 21 to <65 years of age who received Adacel in Study Td506.
Non-inferiority in booster response rate for each pertussis antigen was demonstrated if the lower limit of the 2-sided 95% CI of the difference of booster response rates between participants receiving Adacel in Study Td537 and expected booster response rates based on Study Td506 was >-10%.
PT 693/894 77.5 (74.6; 80.2) 61.4 16.12 (13.27; 18.73)
FHA 651/945 68.9 (65.8; 71.8) 73.1 -4.21 (-7.23; -1.34)
PRN 617/945 65.3 (62.2; 68.3) 83.9 -18.61 (-21.7; -15.6)
FIM 537/945 56.8 (53.6; 60.0) 75.9 -19.07 (-22.3; -16.0)

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