ADACEL POLIO 0.5 ml Suspension for injection in pre-filled syringe

Pharmacotherapeutic group: Bacterial and viral vaccines, combined.‍​‍‍‍​‍‍‍‍‍‍‍‍​‍ Vaccine against diphtheria, pertussis, poliomyelitis and tetanus. ATC code: J07CA02 Clinical trials Immune responses in children aged 3 to 6 years, adolescents and adults, one month after vaccination with Adacel Polio are presented in the table below. Table 2: Immune responses 4 weeks after vaccination with Adacel Polio Antibodies Criterion Children 3-5 years 1 (n = 148) Children 5-6 years 2 (n = 240) Adults and adolescents 3 (n = 994) Diphtheria (SN, IU/ml) ≥ 0.1 100% 99.4% 100% Tetanus (ELISA, IU/ml or EU/ml) 4 ≥ 0.1 100% 99.5% 100% Pertussis (ELISA, EU/ml) Pertussis toxoid Filamentous haemagglutinin 5 micrograms Pertactin 3 micrograms Fimbriae types 2 and 3 5 micrograms ≥ 5 5 99.3% 99.3% 100% 100% 91.2% 99.1% 100% 99.5% 99.7% 99.9% 99.6% 99.8% IPV (SN, titre) Type 1 Type 2 Type 3 ≥ 1:8 100% 100% 100% 100% 100% 100% 99.9% 100% 100% ELISA: enzyme-linked immunosorbent assay; EU: ELISA units; IPV: inactivated polio vaccine; IU: international units; n: number of participants who received ADACEL POLIO; SN: seroneutralisation. 1 Studies U01-Td5I-303 and U02-Td5I-402 were conducted in the UK in children vaccinated with DTwP and OPV at 2, 3 and 4 months of age. Children aged 3.5-5 years were enrolled in U01-Td5I-303. Children aged 3-3.5 years were enrolled in U02-Td5I-402. 2 Swedish Study 5.5 was conducted in Sweden in children aged 5-6 years who had been vaccinated with DTaP and IPV at 3, 5 and 12 months of age. 3 Studies TD9707 and TD9809 were conducted in Canada. TD9707 included adolescents aged 11-17 years and adults aged 18-64 years. Study TD9809 included adolescents aged 11-14 years. 4 Tetanus units differ according to the testing laboratories. For Swedish Study 5.5, units are expressed in IU/ml and for the other studies in EU/ml. 5 Antibody levels ≥ 5 EU/ml were considered as possible surrogate markers for protection against pertussis according to Storsaeter J. et al, Vaccine 1998;16:1907-16. The use of ADACEL POLIO in children aged 3 to 6 years is based on studies in which ADACEL POLIO was administered as the fourth dose (first booster dose) of diphtheria, tetanus, pertussis and poliomyelitis vaccine. After a single dose of ADACEL POLIO, a robust immune response was observed in children who had received primary vaccination in infancy with either whole-cell pertussis vaccine (DTwP) and OPV (UK studies; age 5-6 years) or acellular pertussis vaccine (DTaP) and IPV (Swedish study; age 5-6 years). The safety and immunogenicity of ADACEL POLIO in adults and adolescents was shown to be comparable to that observed after a single booster dose of adsorbed diphtheria and tetanus vaccine (dT) or adsorbed dT-IPV vaccine containing similar amounts of tetanus and diphtheria toxoids and inactivated poliovirus types 1, 2 and 3. The lower response to diphtheria toxoid in adults probably reflects the enrolment of some participants with unknown vaccination status or incomplete vaccination. Serological correlates of protection against pertussis have not been established. Based on comparison with data from the Sweden I pertussis efficacy trials conducted between 1992 and 1996, where primary vaccination with a paediatric DTaP vaccine containing Sanofi Pasteur's acellular pertussis component confirmed 85% protective efficacy against pertussis disease, it can be concluded that ADACEL POLIO elicited protective immune responses in children, adolescents and adults in clinical trials. Persistence of antibodies Pivotal studies conducted with ADACEL provided follow-up serological data at 3, 5 and 10 years in individuals previously vaccinated with a single booster dose of ADACEL. Persistence of seroprotection against diphtheria and tetanus and seropositivity against pertussis is summarised in Table 3. Table 3: Rate of persistence of seroprotection/seropositivity (%) in children, adolescents and adults at 3, 5 and 10 years after administration of a dose of ADACEL (dTaP component of ADACEL POLIO) (PPI population 1 ) Children (4 - 6 years) 2 Adolescents (11 - 17 years) 3 Adults (18 - 64 years) 3 Time from administration of ADACEL dose 5 years 3 years 5 years 10 years 3 years 5 years 10 years Participants N = 128 -150 N = 300 N = 204 - 206 N = 28 - 39 N = 292 N = 237-238 N = 120-136 Antibodies % seroprotection/seropositivity Diphtheria (SN, IU/ml) ≥ 0.1 86.0 97.0 95.1 94.9 81.2 81.1 84.6 ≥ 0.01 100 100 100 100 95.2 93.7 99.3 Tetanus (ELISA, IU/ml) ≥ 0.1 97.3 100 100 100 99.0 97.1 100 Pertussis (ELISA, EU/ml) Sero-positivity 4 PT 63.3 97.3 85.4 82.1 94.2 89.1 85.8 FHA 97.3 100 99.5 100 99.3 100 100 PRN 95.3 99.7 98.5 100 98.6 97.1 99.3 FIM 98.7 98.3 99.5 100 93.5 99.6 98.5 ELISA: enzyme-linked immunosorbent assay; EU: ELISA units; N = number of participants with available data; PPI: per protocol immunogenicity; SN: seroneutralisation; 1 Eligible participants for whom immunogenicity data were available for at least one antibody at a given time point. 2 Study Td508 was conducted in Canada in children aged 4-6 years. 3 Study Td506 was conducted in the United States in adolescents aged 11-17 years and adults aged 18-64 years. 4 Percentage of participants with antibodies ≥ 5 EU/ml for PT, ≥ 3 for FHA and PRN and ≥ 17 EU/ml for FIM for 3-year follow-up; ≥ 4 EU/ml for PT, PRN and FIM and ≥ 3 EU/ml for FHA for 5-year and 10-year follow-up. Follow-up studies conducted with ADACEL POLIO provide serological data at year 1, 3, 5 and 10 in individuals previously immunised with a single booster dose of ADACEL POLIO. Persistence of seroprotection against diphtheria and tetanus, seropositivity against pertussis components and seroprotective antibody levels (≥1:8 dilution) for each poliovirus (type 1, 2 and 3) is summarised in Table 4. Table 4: Rate of persistence of seroprotection/seropositivity (%) in children, adolescents and adults at 1, 3, 5 and 10 years after administration of a dose of ADACEL POLIO (ITT population 1 ) Children (3.5-5 years) 2 Adolescents (11-17 years) 2 Adults (18-64 years) 2 Time from administration of ADACEL POLIO dose 1 year 3 years 5 years 1 year 3 years 5 years 10 years 1 year 3 years 5 years 10 years Participants N= 36-37 N= 36 N= 38-48 N=64 N=117 N=108 N= 97-107 N=32 N= 135-136 N=127 N= 67-79 Antibodies % seroprotection/seropositivity Diphtheria (SN, IU/ml) ≥ 0.1 89.2 72.2 75.0 71.9 85.2 77.1 68.5 62.5 55.6 35.2 32.9 ≥ 0.01 100 100 100 100 99.1 96.2 99.1 90.6 91.9 79.2 84.8 Tetanus (ELISA, IU/ml) ≥ 0.1 100 100 100 100 100 100 97.2 100 97.8 98.4 93.7 Pertussis (ELISA, EU/ml) Seropositivity 3,4 PT 89.2 61.1 55.3 98.4 96.6 99.1 87.6 100 97.1 97.6 91.0 FHA 100 94.4 100 100 99.1 99.1 98.1 100 100 100 100 PRN 97.3 91.7 95.7 100 99.1 100 88.8 100 99.3 98.4 93.7 FIM 100 100 95.7 98.4 98.3 98.1 100 93.8 94.1 93.7 98.7 IPV (SN, titre) ≥ 1:8 Type 1 100 100 97.9 98.4 100 100 NA 100 100 100 NA Type 2 100 100 100 100 100 100 NA 100 100 100 NA Type 3 100 97.2 95.7 98.4 100 98.2 NA 100 100 100 NA ELISA: enzyme-linked immunosorbent assay; EU: ELISA units; IPV: inactivated polio vaccine; ITT: intention to treat, IU: international units; N: number of participants with available data; NA: not analysed; SN: seroneutralisation. 1 ITT population: Study U01-Td5I-303-LT: Eligible participants for whom immunogenicity data were available for at least one antibody at a given time point and at year 5. Study TD9707-LT: Eligible participants for whom immunogenicity data were available for at least one antibody at a given time point. 2 Study U01-Td5I-303-LT was conducted in the UK in children aged 3.5-5 years; Study TD9707-LT was conducted in Canada in adolescents aged 11-17 years and adults aged 18-64 years. 3 For U01-Td5I-303-LT: percentage of participants with antibodies ≥ 5 EU/ml for PT, ≥ 3 for FHA and ≥ 4 for PRN and FIM for 1-year follow-up; ≥ 4 EU/ml for PT, FIM and PRN and ≥ 3 EU/ml for FHA for 3-year and 5-year follow-up. 4 For TD9707-LT: percentage of participants with antibodies ≥ 5 EU/ml for PT, ≥ 3 EU/ml for FHA and PRN and ≥ 17 EU/ml for FIM for all time periods except 10 years; ≥ 4 EU/ml for PT, FIM and PRN and ≥ 3 EU/ml for FHA for 10-year follow-up. Immunogenicity after revaccination Immunogenicity after revaccination 10 years after the last dose of ADACEL or ADACEL POLIO was evaluated. One month after vaccination, ≥ 98.5% of study participants achieved seroprotective antibody levels (≥ 0.1 IU/ml) against diphtheria and tetanus, and ≥ 84% achieved a booster response to pertussis antigens. (Booster response to pertussis was defined as a post-vaccination antibody concentration equal to or greater than 4-fold the LLOQ if the pre-vaccination level was < LLOQ (Lower Limit Of Quantification); ≥ 4-fold the pre-vaccination level if this was ≥ LLOQ but < 4-fold the LLOQ; or ≥ 2-fold the pre-vaccination level if this was ≥ 4-fold the LLOQ). Based on follow-up serological data and revaccination data, ADACEL POLIO can be used instead of dT vaccine or dT-IPV vaccine to boost immunity against pertussis, in addition to diphtheria, tetanus and poliomyelitis. Immunogenicity in previously unvaccinated individuals After administration of a single dose of ADACEL POLIO to 330 adults aged 40 years and older who had not received any diphtheria and tetanus vaccine during the previous 20 years: ≥ 95.8% of adults were seropositive (≥ 5 IU/ml) for antibodies against all pertussis antigens contained in the vaccine, 82.4% and 92.7% were seroprotected against diphtheria with cut-off values of ≥ 0.1 and ≥ 0.01 IU/ml respectively, 98.5% and 99.7% were seroprotected against tetanus with cut-off values of ≥ 0.1 and ≥ 0.01 IU/ml respectively, and ≥ 98.8% were seroprotected against polio (type 1, 2 and 3) with a cut-off of ≥ 1:8 dilution. After administration of two additional doses of diphtheria, tetanus and poliomyelitis vaccine to 316 individuals, one month and six months after the first dose, the seroprotection rate against diphtheria was 94.6% and 100% (≥ 0.1 and ≥ 0.01 IU/ml, respectively), against tetanus 100% (≥ 0.1 IU/ml) and against poliomyelitis (type 1, 2 and 3) 100% (≥ 1:8 dilution) (see Table 4). Table 5: Serological immune status (seroprotection/seroresponse rate and GMC/GMT) before vaccination and after each dose of a 3-dose vaccination schedule, including ADACEL POLIO (dose 1), followed by 2 doses of REVAXIS vaccine at 1 and 6 months later (dose 2 and 3) in per-protocol vaccinated individuals (FAS) Antigen Criterion Pre-vaccination Post dose 1 ADACEL POLIO Post dose 2 REVAXIS Post dose 3 REVAXIS N=330 N=330 N=325 N=316 Diphtheria GMC 0.059 0.813 1.373 1.489 (SN, IU/ml) 95% CI [0.046; 0.077] [0.624; 1.059] [1.100; 1.715] [1.262; 1.757] ≥ 0.1 44.5% 82.4% 90.5% 94.6% 95% CI [39.1; 50.1] [77.9; 86.4] [86.7; 93.4] [91.5; 96.8] ≥ 0.01 72.4% 92.7% 96.0% 100% 95% CI [67.3; 77.2] [89.4; 95.3] [93.3; 97.9] [98.8; 100] Tetanus GMC 0.48 6.82 7.60 5.46 (ELISA, IU/ml) 95% CI [0.39;0.60] [5.92;7.87] [6.77;8.52] [5.01;5.96] ≥ 0.1 81.2% 98.5% 100% 100% 95% CI [76.6; 85.3] [96.5; 99.5] [98.9; 100] [98.8; 100] ≥ 0.01 92.4% 99.7% 100% 100% 95% CI [89.0; 95.0] [98.3; 100] [98.9; 100] [98.8; 100] Poliomyelitis (SN, 1/dil) Type 1 GMT 162.6 2869.0 2320.2 1601.9 95% CI [133.6; 198.0] [2432.9; 3383.4] [2010.9; 2677.0] [1425.4; 1800.3] ≥ 8 93.3% 99.4% 100% 100% 95% CI [90.1; 95.8] [97.8; 99.9] [98.9; 100] [98.8; 100] Type 2 GMT 164.5 3829.7 3256.0 2107.2 95% CI [137.6;196.8] [3258.5;4501.1] [2818.2;3761.7] [1855.7;2392.8] ≥ 8 95.5% 100% 100% 100% 95% CI [92.6; 97.4] [98.9; 100] [98.9; 100] [98.8; 100] Type 3 GMT 69.0 5011.4 3615.6 2125.8 95% CI [56.9; 83.6] [4177.4; 6012.0] [3100.5; 4216.4] [1875.5; 2409.6] ≥ 8 89.1% 98.8% 99.7% 100% 95% CI [85.2; 92.2] [96.9; 99.7] [98.3; 100] [98.8; 100] Pertussis (ELISA, EU/ml) PT GMC 7.7 41.3 95% CI [6.8; 8.7] [36.7; 46.5] ≥ 5 - 96.3% - - 95% CI [93.6; 98.1] FHA GMC 28.5 186.7 95% CI [25.5; 31.8] [169.6; 205.6] ≥ 5 - 100% - - 95% CI [98.9; 100] PRN GMC 7.7 328.6 95% CI [6.7; 8.9] [273.0; 395.6] ≥ 5 - 99.4% - - 95% CI [97.8; 99.9] FIM GMC 6.1 149.6 95% CI [5.2; 7.1] [123.6; 181.0] ≥ 5 - 95.8% - - 95% CI [93.0; 97.7] GMC: Geometric mean antibody concentration; GMT: Geometric mean antibody titre; CI: Confidence interval; SN: seroneutralisation; ELISA: Enzyme-linked immunosorbent assay; dil: dilution FAS: Full analysis set – includes all individuals who received a dose of vaccine in the study and for whom post-vaccination immunogenicity could be assessed. Immunogenicity in pregnant women Pertussis antibody responses in pregnant women are generally similar to those observed in non-pregnant women. Vaccination during the second or third trimester of pregnancy is optimal for antibody transfer to the developing foetus. Pertussis immunogenicity in infants (<3 months) born to women vaccinated during pregnancy Data from 2 published randomised controlled trials demonstrated higher pertussis antibody concentrations at birth and at 2 months of age (i.e. before initiation of primary vaccination) in infants of women who were vaccinated with ADACEL POLIO during pregnancy, compared to women who were not vaccinated against pertussis during pregnancy. In the first study, 33 pregnant women received ADACEL POLIO at 30 to 32 weeks of gestation and 15 received saline placebo. Geometric mean concentrations (GMC) reported in EU/ml for pertussis antibodies to PT, FHA, PRN and FIM antigens in infants of vaccinated women were 68.8, 234.2, 226.8 and 1867.0 respectively at birth and 20.6, 99.1, 75.7 and 510.4 respectively at 2 months of age. In the control group of infants, the corresponding GMC values were 14.0, 25.1, 14.4 and 48.5 at birth and 5.3, 6.6, 5.2 and 12.0 at 2 months of age. The GMC ratio (ADACEL POLIO/control group) was 4.9, 9.3, 15.8 and 38.5 respectively at birth and 3.9, 15.0, 14.6 and 42.5 respectively at 2 months of age. In the second study, 134 pregnant women received ADACEL POLIO and 138 received a control diphtheria and tetanus vaccine, at a mean gestational age of 34.5 weeks. GMC (EU/ml) for pertussis antibodies to PT, FHA, PRN and FIM antigens in infants of vaccinated women were 54.2, 184.2, 294.1 and 939.6 respectively at birth and 14.1, 51.0, 76.8 and 220.0 respectively at 2 months of age. In the control group of infants, the corresponding GMC values were 9.5, 21.4, 11.2 and 31.5 respectively at birth and 3.6, 6.1, 4.4 and 9.0 respectively at 2 months of age. The GMC ratio (ADACEL POLIO/control group) was 5.7, 8.6, 26.3 and 29.8 respectively at birth and 3.9, 8.4, 17.5 and 24.4 respectively at 2 months of age. These higher antibody concentrations provide passive immunity against pertussis in infants during the first 2 to 3 months of life, as demonstrated in observational effectiveness studies. Immunogenicity in infants and toddlers born to women vaccinated during pregnancy The immunogenicity of routine infant vaccination was evaluated in infants of women who were vaccinated with Adacel or ADACEL POLIO during pregnancy, in several published studies. Data on infant responses to pertussis and non-pertussis antigens were assessed during the first year of life. Maternal antibodies acquired from vaccination with Adacel or ADACEL POLIO during pregnancy may be associated with blunting of the infant immune response to active immunisation against pertussis. Based on current epidemiological studies, this blunting is not clinically significant. Data from several studies did not demonstrate any clinically relevant blunting from maternal vaccination with Adacel or ADACEL POLIO, nor suppression of infant or toddler immune responses to diphtheria, tetanus, Haemophilus influenzae type b, inactivated poliovirus or pneumococcal antigens. Effectiveness against pertussis in infants born to women vaccinated during pregnancy Vaccine effectiveness in the first 2-3 months of life of infants born to women vaccinated against pertussis during the third trimester of pregnancy was evaluated in 3 observational studies. Overall effectiveness is > 90%. Table 6: Vaccine effectiveness (VE) against pertussis in infants born to mothers vaccinated during pregnancy with ADACEL POLIO or ADACEL in 3 retrospective studies. Study location Vaccine VE (95% CI) Method of vaccine effectiveness estimation Infant follow-up period UK ADACEL POLIO 93% (81, 97) unmatched case-control 2 months US ADACEL* 91.4% (19.5; 99.1) cohort regression model 2 months UK ADACEL POLIO 93% (89, 95) screening (case coverage) 3 months * Approximately 99% of women were vaccinated with ADACEL