Pandemic H5N1 Influenza
Conditions
Keywords
Influenza, Pandemic, H5N1, Children
Brief summary
Evaluate Safety, Tolerability and Immune response of adjuvanted H5N1 cell culture derived influenza vaccine in children.
Interventions
Comparison of two doses of aH5N1c vaccine
Sponsors
Department of Health and Human Services
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy pediatric subjects 6 months to 17 years of age, 2. Individuals' parent(s) or legal guardian(s) willing to provide written informed consent, 3. Individuals in good health, 4. Individuals/Individuals' parent(s)/legal guardian(s) willing to allow for serum samples to be stored beyond the study period, 5. Individuals willing to provide informed assent (where applicable).
Exclusion criteria
1. Individuals' parent(s)/legal guardian(s) not able to understand and follow study procedures, 2. History of any significant illness, 3. History of any chronic medical condition or progressive disease, 4. Presence of medically significant cancer, 5. Known or suspected impairment/alteration of immune function, 6. Presence of any progressive or severe neurologic disorder, 7. Presence of any bleeding disorders or conditions that prolongs bleeding time, 8. History of allergy to vaccine components, 9. Receipt of any other investigational product within 30 days prior to entry into the study, 10. History of previous H5N1 vaccination, 11. Receipt of any other type of seasonal vaccination within 2 months prior to entry into the study, 12. Receipt of any other vaccine within 2 weeks prior to entry into the study, 13. Body temperature ≥38°C (≥100.4° F) and/or acute illness within 3 days of intended study vaccination, 14. Pregnant or breast feeding, 15. Females of childbearing potential refusing to use acceptable method of birth control, 16. Body mass index (BMI) ≥ 35 kg/m2, 17. History of drug or alcohol abuse, 18. Any planned surgery during study period, 19. Individuals conducting the study and their immediate family members, 20. Individuals with behavioral or cognitive impairment or psychiatric diseases, 21. Individuals diagnosed with any growth disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Any unsolicited AEs - day 1 through day 22 after any vaccination; SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387 | Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine. |
| The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain | Three weeks after 2nd vaccination (day 43) | The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 6 to \<36 months, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%. |
| The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Three weeks after 2nd vaccination (day 43) | The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 3 to \<9 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%. |
| The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Three weeks after 2nd vaccination (day 43) | The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 9 to \<18 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%. |
| The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Three weeks after 2nd vaccination (day 43) | Immunogenicity was measured in terms of the percentages of subjects aged 6 to \<36 months, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%. |
| The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Three weeks after 2nd vaccination (day 43) | Immunogenicity was measured in terms of the percentages of subjects aged 3 to \<9 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%. |
| The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Three weeks after 2nd vaccination (day 43) | Immunogenicity was measured in terms of the percentages of subjects aged 9 to \<18 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%. |
| Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | From day 1 through day 7 after each vaccination. | Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine. |
| Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | From day 1 through day 7 after any vaccination. | Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | Day 1, day 22, day 43 and day 387 | Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 6 to \<36 months is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. |
| Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | Day 1, day 22, day 43 and day 387 | Immunogenicity was measured as geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 3 to \<9 years is reported. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5. |
| Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | Day 1, day 22, day 43 and day 387 | Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 9 to \<18 years is reported. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5. |
| Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 1, day 22, day 43 and day 387. | Immunogenicity was assessed in terms of percentage of subjects aged 6 to \<36 months, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%. |
| Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 1, day 22, day 43 and day 387. | Immunogenicity was assessed in terms of percentage of subjects aged 3 to \<9 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%. |
| Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 1, day 22, day 43 and day 387. | Immunogenicity was assessed in terms of percentage of subjects aged 9 to \<18 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%. |
| The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 22, day 43 and day 387 | Immunogenicity was assessed in terms of percentages of subjects aged 6 to \<36 months achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%. |
| The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 22, day 43 and day 387 | Immunogenicity was assessed in terms of percentages of subjects aged 3 to \<9 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%. |
| The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 22, day 43 and day 387 | Immunogenicity was assessed in terms of percentages of subjects aged 9 to \<18 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%. |
Countries
Thailand, United States
Participant flow
Recruitment details
Subjects were enrolled at 10 centers in United States and 2 centers in Thailand.
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| High Dose Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. | 332 |
| Low Dose Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. | 330 |
| Total | 662 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Reason | 2 | 5 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 6 | 9 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Unclassified | 4 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 8 |
Baseline characteristics
| Characteristic | High Dose | Low Dose | Total |
|---|---|---|---|
| Age, Continuous | 78.7 Months STANDARD_DEVIATION 55.9 | 78.1 Months STANDARD_DEVIATION 55.6 | 78.4 Months STANDARD_DEVIATION 55.7 |
| Sex: Female, Male FEMALE | 152 Participants | 164 Participants | 316 Participants |
| Sex: Female, Male MALE | 180 Participants | 166 Participants | 346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 263 / 329 | 257 / 329 | 520 / 658 |
| serious Total, serious adverse events | 8 / 329 | 11 / 329 | 19 / 658 |
Outcome results
Primary
Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination
Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.
Time frame: From day 1 through day 7 after each vaccination.
Population: Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site induration (N=159,162) | 2 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Irritability (N=159,162) | 47 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site tenderness (N=159,162) | 89 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Sleepiness (N=159,162) | 40 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site erythema (N=159,162) | 4 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥38°C; N=160,162) | 25 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Systemic | 68 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Prevention of pain and/or fever (N=160,161) | 18 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site ecchymosis (N=159,162) | 0 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Treatment of pain and/or fever (N=160,161) | 37 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Change in eating habits (N=159,162) | 29 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥40°C; N=160,162) | 1 Number of subjects |
| High Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Local | 89 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥40°C; N=160,162) | 0 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Local | 92 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site erythema (N=159,162) | 2 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site induration (N=159,162) | 2 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site ecchymosis (N=159,162) | 1 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site tenderness (N=159,162) | 91 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Systemic | 65 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Change in eating habits (N=159,162) | 20 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Irritability (N=159,162) | 45 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Sleepiness (N=159,162) | 40 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥38°C; N=160,162) | 13 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Prevention of pain and/or fever (N=160,161) | 25 Number of subjects |
| Low Dose | Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Treatment of pain and/or fever (N=160,161) | 26 Number of subjects |
Primary
Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination
Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.
Time frame: From day 1 through day 7 after any vaccination.
Population: Analysis was done on the safety dataset.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Nausea (N=162,160) | 21 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Local | 111 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site erythema (N=163,161) | 2 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site induration (N=163,160) | 4 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site ecchymosis (N=163,160) | 0 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site pain (N=163,160) | 111 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Systemic | 79 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Myalgia (N=162,160) | 49 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Arthralgia (N=162,160) | 21 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Headache (N=162,160) | 36 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fatigue (N=162,160) | 43 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Loss of Appetite (N=162,160) | 22 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Malaise (N=162,160) | 40 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥38°C; N=163,161) | 7 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Prevention of pain and/or fever (N=163,161) | 14 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Treatment of pain and/or fever (N=163,161) | 24 Number of subjects |
| High Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥40°C; N=163,161) | 0 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥38°C; N=163,161) | 5 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Headache (N=162,160) | 47 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Local | 115 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Nausea (N=162,160) | 26 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site erythema (N=163,161) | 0 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fatigue (N=162,160) | 48 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site induration (N=163,160) | 2 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Prevention of pain and/or fever (N=163,161) | 10 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site ecchymosis (N=163,160) | 0 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Loss of Appetite (N=162,160) | 18 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Injection site pain (N=163,160) | 115 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Fever (≥40°C; N=163,161) | 0 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Any Systemic | 82 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Malaise (N=162,160) | 38 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Myalgia (N=162,160) | 44 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Treatment of pain and/or fever (N=163,161) | 23 Number of subjects |
| Low Dose | Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination | Arthralgia (N=162,160) | 19 Number of subjects |
Primary
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination
Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.
Time frame: Any unsolicited AEs - day 1 through day 22 after any vaccination; SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387
Population: Analysis was done on the safety dataset.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Any SAEs (N=326,324) | 8 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Medically attended AEs (N=326,324) | 110 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | AEs resulting in premature withdrawal (N=326,324) | 1 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | At least possibly related AEs (N=326,324) | 15 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | AEs of Special Interest (N=326,324) | 0 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Deaths (N=326,324) | 0 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | New Onset of Chronic Disease(N=326,324) | 0 Number of subjects |
| High Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Any AEs | 149 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | New Onset of Chronic Disease(N=326,324) | 3 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Medically attended AEs (N=326,324) | 113 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Any AEs | 156 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | At least possibly related AEs (N=326,324) | 12 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Any SAEs (N=326,324) | 11 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | Deaths (N=326,324) | 0 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | AEs resulting in premature withdrawal (N=326,324) | 0 Number of subjects |
| Low Dose | Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination | AEs of Special Interest (N=326,324) | 0 Number of subjects |
Primary
The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain
The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 3 to \<9 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
Time frame: Three weeks after 2nd vaccination (day 43)
Population: Analysis was done on FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 0 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=94,98) | 98 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 0 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=94,98) | 86 Percentages of subjects |
Primary
The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain
Immunogenicity was measured in terms of the percentages of subjects aged 3 to \<9 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
Time frame: Three weeks after 2nd vaccination (day 43)
Population: Analysis was done on FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | 98 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | 86 Percentages of subjects |
Primary
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain
The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 6 to \<36 months, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
Time frame: Three weeks after 2nd vaccination (day 43)
Population: Analysis was done on the Full Analysis Set (FAS) i.e., the subjects who actually received at least one dose of study vaccination and provided at least one evaluable serum sample both before (baseline) and after vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain | Day 1 | 1 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain | Day 43 (N=91,85) | 98 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain | Day 1 | 0 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain | Day 43 (N=91,85) | 94 Percentages of subjects |
Primary
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain
Immunogenicity was measured in terms of the percentages of subjects aged 6 to \<36 months, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
Time frame: Three weeks after 2nd vaccination (day 43)
Population: Analysis was done was FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | 99 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | 94 Percentages of subjects |
Primary
The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain
The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 9 to \<18 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
Time frame: Three weeks after 2nd vaccination (day 43)
Population: Analysis was done on FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 2 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=102,105) | 92 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 1 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=102,105) | 79 Percentages of subjects |
Primary
The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain
Immunogenicity was measured in terms of the percentages of subjects aged 9 to \<18 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
Time frame: Three weeks after 2nd vaccination (day 43)
Population: This analysis was done on the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | 92 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | 79 Percentages of subjects |
Secondary
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years.
Immunogenicity was measured as geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 3 to \<9 years is reported. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5.
Time frame: Day 1, day 22, day 43 and day 387
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | A/H5N1 (Day22/Day1) | 9.81 Ratio |
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | A/H5N1 (Day43/Day1; N=93,98) | 249 Ratio |
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | A/H5N1 (Day387/Day1; N=89,94) | 11 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | A/H5N1 (Day22/Day1) | 8.22 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | A/H5N1 (Day43/Day1; N=93,98) | 73 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. | A/H5N1 (Day387/Day1; N=89,94) | 4.62 Ratio |
Secondary
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months.
Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 6 to \<36 months is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.
Time frame: Day 1, day 22, day 43 and day 387
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | A/H5N1 (Day22/Day1) | 12 Ratio |
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | A/H5N1 (Day43/Day1; N=84,85) | 302 Ratio |
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | A/H5N1 (Day387/Day1; N=78,77) | 52 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | A/H5N1 (Day22/Day1) | 4.56 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | A/H5N1 (Day43/Day1; N=84,85) | 116 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. | A/H5N1 (Day387/Day1; N=78,77) | 19 Ratio |
Secondary
Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years.
Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 9 to \<18 years is reported. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is \>2.5.
Time frame: Day 1, day 22, day 43 and day 387
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | A/H5N1 (Day22/Day1; N=102,103) | 15 Ratio |
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | A/H5N1 (Day43/Day1) | 186 Ratio |
| High Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | A/H5N1 (Day387/Day1; N=97,100) | 4.05 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | A/H5N1 (Day22/Day1; N=102,103) | 6.74 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | A/H5N1 (Day43/Day1) | 58 Ratio |
| Low Dose | Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. | A/H5N1 (Day387/Day1; N=97,100) | 2.64 Ratio |
Secondary
Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain
Immunogenicity was assessed in terms of percentage of subjects aged 3 to \<9 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%.
Time frame: Day 1, day 22, day 43 and day 387.
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 0 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 22 (N=96,98) | 43 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=94,98) | 98 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 387 (90,94) | 44 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 387 (90,94) | 22 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 0 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=94,98) | 86 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 22 (N=96,98) | 41 Percentages of subjects |
Secondary
Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain
Immunogenicity was assessed in terms of percentage of subjects aged 6 to \<36 months, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%.
Time frame: Day 1, day 22, day 43 and day 387.
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 1 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 22 (N=85,86) | 58 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=91,85) | 98 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 387 (N=84,77) | 71 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 387 (N=84,77) | 61 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 0 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=91,85) | 94 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain | Day 22 (N=85,86) | 36 Percentages of subjects |
Secondary
Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain
Immunogenicity was assessed in terms of percentage of subjects aged 9 to \<18 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is \>70%.
Time frame: Day 1, day 22, day 43 and day 387.
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 2 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 22 (N=102,103) | 54 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=102,105) | 92 Percentages of subjects |
| High Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 387 (N=97,100) | 29 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 387 (N=97,100) | 17 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 1 | 1 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 43 (N=102,105) | 79 Percentages of subjects |
| Low Dose | Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain | Day 22 (N=102,103) | 37 Percentages of subjects |
Secondary
The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain
Immunogenicity was assessed in terms of percentages of subjects aged 3 to \<9 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%.
Time frame: Day 22, day 43 and day 387
Population: Analysis was done on FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 22 | 43 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 43 (N=93,98) | 98 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 387 (N=89,94) | 45 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 22 | 41 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 43 (N=93,98) | 86 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 387 (N=89,94) | 22 Percentages of subjects |
Secondary
The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain
Immunogenicity was assessed in terms of percentages of subjects aged 6 to \<36 months achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%.
Time frame: Day 22, day 43 and day 387
Population: Analysis was done on the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 22 | 58 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 43 (N=84,85) | 99 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 387 (N=78,77) | 73 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 22 | 36 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 43 (N=84,85) | 94 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain | Day 387 (N=78,77) | 61 Percentages of subjects |
Secondary
The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain
Immunogenicity was assessed in terms of percentages of subjects aged 9 to \<18 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is \>40%.
Time frame: Day 22, day 43 and day 387
Population: Analysis was done the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 22 (N=102,103) | 54 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 43 | 92 Percentages of subjects |
| High Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 387 (N=97,100) | 29 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 22 (N=102,103) | 36 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 43 | 79 Percentages of subjects |
| Low Dose | The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain | Day 387 (N=97,100) | 16 Percentages of subjects |