Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02.
Mechanism of action:
Influvac Tetra provides active immunisation against four influenza virus strains: an A/(H1N1) strain, an A/(H3N2) strain, and two B strains (one from each lineage; B/(Victoria) and B/(Yamagata)).
Influvac Tetra, manufactured according to the same process as trivalent influenza vaccine Influvac, induces humoral antibodies against the haemagglutinins. These antibodies neutralise influenza viruses.
Specific levels of hemagglutination-inhibition (HI) antibody titer post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness but the HI antibody titers have been used as a measure of vaccine activity.
An immune response is generally obtained within 2 to 3 weeks. The duration of postvaccinal immunity to homologous strains or to strains closely related to the vaccine strains varies but is usually 6-12 months.
Pharmacodynamic effects:
Efficacy of Influvac Tetra in children 6 - 35 months of age:
The efficacy of Influvac Tetra was evaluated in a randomized, observer-blind, non-influenza vaccine-controlled study (INFQ3003) conducted during 3 influenza seasons 2017 to 2019 in Europe and Asia. Healthy subjects aged 6 - 35 months received two doses of Influvac Tetra (N=1005) or non-influenza control vaccine (N=995) approximately 28 days apart. The efficacy of Influvac Tetra was assessed for the prevention of reverse transcription polymerase chain reaction (RT-PCR) - confirmed influenza A and/or B disease due to any influenza strain. All RT-PCR-positive specimens were further tested for viability in cell culture and to determine whether the circulating viral strains matched those in the vaccine.
Table: Efficacy in children 6 – 35 months of age

Influvac Tetra        Non-influenza       Vaccine efficacy control-vaccine
N=1005                N=995               (95% CI)
Laboratory-confirmed                n                     n influenza caused by:
- Any influenza A or B              59                    117                 0.54 (0.37 - 0.66) strain
- Culture confirmed                 19                    56                  0.68 (0.45 - 0.81) vaccine matching strains
Vaccine efficacy: proportion of influenza cases prevented by the vaccination N=number of subjects vaccinated n=number of influenza cases
CI=confidence interval



Immunogenicity of Influvac Tetra:
Clinical studies performed in adults of 18 years of age and older (INFQ3001) and children of 3 to 17 years of age (INFQ3002) assessed the safety and immunogenicity of Influvac Tetra and its non- inferiority to trivalent influenza vaccine Influvac for the postvaccination HI Geometric mean antibody titer (GMT).
In both studies the immune response elicited by Influvac Tetra against the three strains in common was non-inferior to trivalent influenza vaccine Influvac. Influvac Tetra elicited a superior immune response against the additional B strain included in Influvac Tetra compared to trivalent influenza vaccine Influvac.
Adults 18 years of age and older:
In clinical study INFQ3001, 1,535 adults of 18 years of age and older received a single dose of Influvac Tetra and 442 subjects received a single dose of trivalent Influvac:
Table: Post-vaccination GMT and Seroconversion rates
Adults 18 – 60        Influvac Tetra              Influvac1                  Influvac2 years of age          N=768                       N=112                      N=110 GMT (95% confidence interval)
A/H1N1                272.2   (248.0 , 298.8)     304.4 (235.1 , 394.1)      316.0 (245.1 , 407.3) A/H3N2                442.4   (407.6 , 480.2)     536.5 (421.7 , 682.6)      417.0 (323.7 , 537.1) B (Yamagata)3         162.5   (147.8 , 178.7)     128.7 (100.3 , 165.2)       81.7     (60.7 , 109.9) B (Victoria)4         214.0   (195.5 , 234.3)      85.1     (62.6 , 115.6)   184.7 (139.0 , 245.3) Seroconversion Rates (95% confidence interval)
A/H1N1                59.4%    (55.8% , 62.9%)    65.5% (55.8% , 74.3%)      64.8% (55.0% , 73.8%) A/H3N2                51.3%    (47.7% , 54.9%)    61.6% (51.9% , 70.6%)      55.5% (45.7% , 64.9%) B (Yamagata)3         59.2%    (55.7% , 62.8%)    58.7% (48.9% , 68.1%)      40.9% (31.6% , 50.7%) B (Victoria)4         70.2%    (66.8% , 73.4%)    51.4% (41.6% , 61.1%)      66.4% (56.7% , 75.1%) 

Elderly 61 years      Influvac Tetra            Influvac1                 Influvac2 of age and older      N=765                     N=108                     N=110 GMT (95% confidence interval)
A/H1N1                127.2 (114.9 , 140.9)     142.4 (107.6 , 188.3)     174.2 (135.9 , 223.3) A/H3N2                348.5 (316.8 , 383.5)     361.5 (278.3 , 469.6)     353.4 (280.7 , 445.0) B (Yamagata)3          63.7 (57.7 , 70.4)        57.4 (43.6 , 75.7)         27.3 (20.7 , 36.0) B (Victoria)4         109.4 (98.1 , 122.0)       48.0 (34.6 , 66.6)       106.6 (79.7 , 142.8) Seroconversion Rates (95% confidence interval)
A/H1N1                50.3% (46.7% , 54.0%)     56.6% (46.6% , 66.2%)     58.2% (48.4% , 67.5%) A/H3N2                39.3% (35.8% , 42.9%)     44.4% (34.9% , 54.3%)     43.6% (34.2% , 53.4%) B (Yamagata)3         49.9% (46.2% , 53.5%)     46.2% (36.5% , 56.2%)     30.0% (21.6% , 39.5%) B (Victoria)4         53.6% (50.0% , 57.2%)     25.0% (17.2% , 34.3%)     55.6% (45.7% , 65.1%) N= number of subjects included in immunogenicity analysis
1 containing A/H1N1, A/H3N2 and B (Yamagata lineage)
2 containing A/H1N1, A/H3N2 and B (Victoria lineage)
3 recommended B strain by WHO for the season 2014-2015 NH for trivalent vaccines 4 additional recommended B strain by WHO for season 2014-2015 NH for quadrivalent vaccines 
Paediatric population
Children 3 - 17 years of age:
In clinical study INFQ3002, 402 children of 3 to 17 years of age received one or two doses of Influvac Tetra and 798 children received one or two doses of trivalent Influvac based on their influenza vaccination history.

Table: Seroconversion rates
Children 3 -         Influvac Tetra               Influvac1                  Influvac2 17 years of age      N=396                        N=389                      N=399 Seroconversion Rates (95% confidence interval)
A/H1N1               60.1%     (55.1% , 65.0%)    61.8% (56.7% , 66.6%)      59.1% (54.1% , 64.0%) A/H3N2               80.6%     (76.3% , 84.3%)    82.4% (78.3% , 86.1%)      80.7% (76.5% , 84.5%) B (Yamagata)3        79.3%     (75.0% , 83.2%)    73.1% (68.4% , 77.5%)      28.1% (23.7% , 32.8%) B (Victoria)4        76.5%     (72.0% , 80.6%)    39.5% (34.6% , 44.6%)      72.7% (68.0% , 77.0%) N= number of subjects included in immunogenicity analysis
1 containing A/H1N1, A/H3N2 and B (Yamagata lineage)
2 containing A/H1N1, A/H3N2 and B (Victoria lineage)
3 recommended B strain by WHO for the season 2016-2017 NH for trivalent vaccines 4 additional recommended B strain by WHO for season 2016-2017 NH for quadrivalent vaccines 
Children 6 months - 35 months of age:
In clinical study INFQ3003 the immunogenicity of Influvac Tetra was evaluated in terms of seroconversion rates across 3 influenza seasons.
Table: Seroconversion rates
Children 6 -       Influenza season           Influenza season         Influenza season 35 months of       NH 2017-20181              NH 2018-20191            SH 20191 age                N=348                      N=359                    N=225 Seroconversion Rates (95% confidence interval)
A/H1N1             74.4%      (69.5% , 78.9%) 76.0% (71.3% , 80.4%) 69.8% (63.3% , 75.7%) A/H3N2             92.5%      (89.2% , 95.0%) 86.6% (82.7% , 90.0%) 86.2% (81.0% , 90.4%) B (Yamagata)       35.5%      (30.4% , 40.8%) 56.0% (50.7% , 61.2%) 16.9% (12.2% , 22.4%) B (Victoria)       26.5%      (21.9% , 31.5%) 65.2% (60.0% , 70.1%) 47.6% (40.9% , 54.3%) N= number of subjects included in immunogenicity analysis
1 containing recommended strains by WHO for respective season for quadrivalent vaccines 

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Not applicable.