Encephalitis
Conditions
Keywords
Pediatric, Japanese Encephalitis Vaccine, endemic countries, to assess the systemic and local safety profile of purified inactivated Japanese Encephalitis Virus (JEV) vaccine IC51
Brief summary
The primary objective is to assess the systemic and local safety profile of purified inactivated Japanese Encephalitis Virus (JEV) vaccine IC51 administered in two doses in a 28 days interval up to Month 7 after the first IC51 vaccination in a pediatric population from endemic regions.
Detailed description
Open-label, randomized, active controlled Phase 3 study in children aged ≥ 2 months to \< 18 years. Subjects aged ≥ 2 months to \< 12 months were randomized in a 2:1 ratio to receive IC51 (0.25 ml dose) or Prevnar® as a safety comparator. Children aged ≥ 12 months to \< 3 years and ≥ 12 years to \< 18 years were randomized in a 3:1 ratio to receive IC51 (0.25 ml dose \< 3 years, 0.5 ml ≥ 12 years) or HAVRIX®720 as safety comparator. For subjects aged ≥ 3 years to \< 12 years, a dose finding run-in phase was performed. A total of 200 subjects were randomized 1:1 to receive either the 0.25 ml or the 0.5 ml dose of IC51, and the appropriate dose was determined based on an interim analysis. After this run-in phase, 300 further children in this age group were randomized 2:1 to receive either 0.5 ml of IC51 or HAVRIX®720. Immunogenicity was be studied in a subgroup of 30 children aged ≥ 2 months to \< 12 months; 125 children aged ≥ 12 months to \< 3 years and 140 children ≥ 12 years to \< 18 years. For the age group of ≥ 3 to \< 12 years immunogenicity was assessed in the 200 children enrolled during the dose-finding run-in phase.
Interventions
BIOLOGICALIC51 Japanese Encephalitis
6 mcg or 3 mcg im. at day 0 and day 28
BIOLOGICALHavrix®720
0.5 ml im. at day 0 and month 7
BIOLOGICALPrevnar
0.5 ml im. at day 0 and day 56 and month 7
Sponsors
Valneva Austria GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female healthy children and adolescents aged \> 2 months to \< 18 years at the time of first vaccination. * Written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable. * Female subjects: either no childbearing potential or negative pregnancy test, for females after menarche willingness to practice a reliable method of contraception.
Exclusion criteria
* Clinical manifestation of Japanese Encephalitis * History of Flavivirus vaccination (including any investigational vaccines) * History of vaccination with HAVRIX®720 and/or Prevnar® * History of immunodeficiency or immunosuppressive therapy * Known HIV, HBV or HCV infection * History of hypersensitivity reactions to other vaccines * Acute febrile infection at each visit during which the subject receives a vaccination * Active or passive immunization within 2 weeks prior to the first IC51 vaccination and up to the second IC51 vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | until Day 56 | Rate of subjects with these types of AEs, comparison vs respective control vaccine stratified by age group: All study participants aged \< 1 year: IC51 0.25mL vs. Prevnar; All study participants aged 1 year and above: IC51 0.25 mL or =.5 mL vs. Havrix. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Days 0, 56 and at Month 7 | Seroconversion was defined as a PRNT50 titer of at least 1:10. SCRs are presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to \< 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to \< 18 years. |
| Rate of Subjects With SAEs and Medically Attended AEs | up to Month 7 | Rate of subjects with SAEs and medically attended AEs; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year. |
| Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Day 0, 56 and at Month 7 | GMT for JEV neutralizing antibodies is presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to \< 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to \< 18 years. |
| Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Day 56 and up to Month 7 | Rate of subjects with unsolicited AEs up to Day 56 and up to Month 7; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year. |
| Rate of Subjects With Abnormal Laboratory Parameters | Day 56 and Month 7 | Rate of subjects with abnormal laboratory parameters clinically significant results are shown below |
| Rate of Subjects With Solicited Local and Systemic AEs | 7 days post vaccination | Rate of subjects with solicited local and systemic AEs. Solicited AEs of local and systemic tolerability, i.e., reactions at the injection site or systemic reactions typical for vaccinations, were to be evaluated for 7 consecutive days after each vaccination (except after the HAVRIX®750 and Prevnar® injections at Month 7 \[Visit 4\]) and recorded in the subject diary. For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year. |
Countries
Philippines
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IC51 0.25 mL Japanese Encephalitis Vaccine 3mcg i.m. at day 0 and day 28 | 871 |
| IC51 0.5 mL Japanese Encephalitis Vaccine 6mcg i.m. at day 0 and day 28 | 540 |
| Havrix 720 Havrix®720 0.5 ml i.m. at day 0 and month 7 | 394 |
| Prevnar Prevnar 0.5 ml i.m. at day 0 and day 56 and month 7 or 0.5 ml i.m. at day 0, day 28 and day56 and month 7-13 | 64 |
| Total | 1,869 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 |
| Overall Study | further blood extraction | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 | 1 |
| Overall Study | positive to anti-HCV | 1 | 0 | 0 | 0 |
| Overall Study | relocation | 1 | 4 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Prevnar | Havrix 720 | IC51 0.5 mL | IC51 0.25 mL |
|---|---|---|---|---|---|
| Age, Customized 12 years - < 18 years | 320 participants | 0 participants | 80 participants | 240 participants | 0 participants |
| Age, Customized 1 year - < 3 years | 853 participants | 0 participants | 213 participants | 0 participants | 640 participants |
| Age, Customized 2 months - < 1 year | 195 participants | 64 participants | 0 participants | 0 participants | 131 participants |
| Age, Customized 3 years - < 12 years | 501 participants | 0 participants | 101 participants | 300 participants | 100 participants |
| Region of Enrollment Philippines | 1869 participants | 64 participants | 394 participants | 540 participants | 871 participants |
| Sex: Female, Male Female | 925 Participants | 30 Participants | 197 Participants | 249 Participants | 449 Participants |
| Sex: Female, Male Male | 944 Participants | 34 Participants | 197 Participants | 291 Participants | 422 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 691 / 871 | 300 / 540 | 252 / 394 | 57 / 64 |
| serious Total, serious adverse events | 16 / 871 | 7 / 540 | 10 / 394 | 1 / 64 |
Outcome results
Primary
Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination
Rate of subjects with these types of AEs, comparison vs respective control vaccine stratified by age group: All study participants aged \< 1 year: IC51 0.25mL vs. Prevnar; All study participants aged 1 year and above: IC51 0.25 mL or =.5 mL vs. Havrix.
Time frame: until Day 56
Population: As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (\<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | 16.1 percentage of participants |
| Havrix 720 | Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | 14.2 percentage of participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | 38.2 percentage of participants |
| Prevnar | Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | 42.2 percentage of participants |
p-value: 0.641Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies
GMT for JEV neutralizing antibodies is presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to \< 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to \< 18 years.
Time frame: Day 0, 56 and at Month 7
Population: Intent-to-treat Population: all subjects randomized into the immunogenicity subgroup, who received at least 1 vaccination. Subjects were analyzed according to the treatment group to which they were randomized rather than by the actual vaccine they received.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| IC51, Subjects Aged >= 1 Year | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Day 0 | 5.79 Geometric Mean Titer | Standard Deviation 1.802 |
| IC51, Subjects Aged >= 1 Year | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Day 56 | 199.39 Geometric Mean Titer | Standard Deviation 3.387 |
| IC51, Subjects Aged >= 1 Year | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Month 7 | 37.99 Geometric Mean Titer | Standard Deviation 3.267 |
| Havrix 720 | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Month 7 | 64.83 Geometric Mean Titer | Standard Deviation 3.242 |
| Havrix 720 | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Day 0 | 9.78 Geometric Mean Titer | Standard Deviation 2.944 |
| Havrix 720 | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | Day 56 | 190.77 Geometric Mean Titer | Standard Deviation 2.747 |
Secondary
Rate of Subjects With Abnormal Laboratory Parameters
Rate of subjects with abnormal laboratory parameters clinically significant results are shown below
Time frame: Day 56 and Month 7
Population: Urinalysis Evaluations were not mandatory unless the subject was at least 12 years old at V0.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Day 56 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Month 7 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Day 56 | 2 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Month 7 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Day 56 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Month 7 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Month 7 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Day 56 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Day 56 | 8 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Month 7 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Month 7 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Day 56 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Day 56 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Month 7 | 2 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Day 56 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | AST Month 7 | 5 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Month 7 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Month 7 | 7 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | ALT Day 56 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | AST Day 56 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Month 7 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | ALT Month 7 | 4 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Day 56 | 0 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Day 56 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Month 7 | 1 participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Day 56 | 1 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Day 56 | 1 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Day 56 | 1 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Day 56 | 2 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Month 7 | 2 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | AST Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | ALT Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Month 7 | 2 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Day 56 | 2 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Month 7 | 2 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | AST Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | ALT Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Day 56 | 1 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Month 7 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Day 56 | 0 participants |
| Havrix 720 | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Month 7 | 2 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Month 7 | 1 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | ALT Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | ALT Day 56 | 1 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | AST Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | AST Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Month 7 | 1 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Month 7 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Day 56 | 1 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Month 7 | 1 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Day 56 | 0 participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | AST Day 56 | 1 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | ALT Month 7 | 3 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Platelets Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Potassium Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | White Blood Cells Day 56 | 1 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | ALT Day 56 | 1 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Red Blood Cells Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Calcium Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Hemoglobin Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | AST Month 7 | 3 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Creatinine Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Bilirubin Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Alkaline Phosphatase Day 56 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Sodium Month 7 | 0 participants |
| Prevnar | Rate of Subjects With Abnormal Laboratory Parameters | Hematocrit Month 7 | 0 participants |
Secondary
Rate of Subjects With SAEs and Medically Attended AEs
Rate of subjects with SAEs and medically attended AEs; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year.
Time frame: up to Month 7
Population: As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (\<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with SAE | 0.5 percentage of participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with medically attended AE | 16.1 percentage of participants |
| Havrix 720 | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with medically attended AE | 14.2 percentage of participants |
| Havrix 720 | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with SAE | 1.0 percentage of participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with SAE | 0 percentage of participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with medically attended AE | 38.2 percentage of participants |
| Prevnar | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with SAE | 1.6 percentage of participants |
| Prevnar | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with medically attended AE | 42.2 percentage of participants |
Secondary
Rate of Subjects With Solicited Local and Systemic AEs
Rate of subjects with solicited local and systemic AEs. Solicited AEs of local and systemic tolerability, i.e., reactions at the injection site or systemic reactions typical for vaccinations, were to be evaluated for 7 consecutive days after each vaccination (except after the HAVRIX®750 and Prevnar® injections at Month 7 \[Visit 4\]) and recorded in the subject diary. For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year.
Time frame: 7 days post vaccination
Population: As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (\<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Solicited Local and Systemic AEs | 40.8 percentage of participants |
| Havrix 720 | Rate of Subjects With Solicited Local and Systemic AEs | 29.4 percentage of participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Solicited Local and Systemic AEs | 58 percentage of participants |
| Prevnar | Rate of Subjects With Solicited Local and Systemic AEs | 59.4 percentage of participants |
Secondary
Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7
Rate of subjects with unsolicited AEs up to Day 56 and up to Month 7; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged \>= 2 months to \<1 year and Havrix 720 for study participants aged \>= 1 year.
Time frame: Day 56 and up to Month 7
Population: As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (\<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Day 56 | 46.5 percentage of participants |
| IC51, Subjects Aged >= 1 Year | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Month 7 | 58.5 percentage of participants |
| Havrix 720 | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Month 7 | 57.6 percentage of participants |
| Havrix 720 | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Day 56 | 46.4 percentage of participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Day 56 | 72.5 percentage of participants |
| IC51, Subjects Aged >= 2 Months to <1 Year | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Month 7 | 77.1 percentage of participants |
| Prevnar | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Day 56 | 65.6 percentage of participants |
| Prevnar | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Month 7 | 81.3 percentage of participants |
Secondary
Seroconversion Rate (SCR) at Days 0, 56 and at Month 7
Seroconversion was defined as a PRNT50 titer of at least 1:10. SCRs are presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to \< 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to \< 18 years.
Time frame: Days 0, 56 and at Month 7
Population: number analyzed is dependent on number of serum samples available for testing
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IC51, Subjects Aged >= 1 Year | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Day 0 | 7.5 percentage of participants |
| IC51, Subjects Aged >= 1 Year | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Day 56 | 98.0 percentage of participants |
| IC51, Subjects Aged >= 1 Year | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Month 7 | 83.9 percentage of participants |
| Havrix 720 | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Day 0 | 33.6 percentage of participants |
| Havrix 720 | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Day 56 | 100.0 percentage of participants |
| Havrix 720 | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Month 7 | 94.5 percentage of participants |