Japanese Encephalitis
Conditions
Brief summary
The objective is to demonstrate the non-inferiority of the Japanese Encephalitis vaccine IC51 compared to JE-VAX in healthy subjects aged \> or = 18 years
Interventions
BIOLOGICALIC51
IC51 (JE-PIV), 6 mcg, i.m. injection, 2 vaccinations, days 0 and 28
BIOLOGICALJE-VAX
JE-VAX, 1mL s.c. injection, 3 vaccinations, days 0, 7 and 28
Sponsors
Valneva Austria GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* At least 18 years of age * Written informed consent obtained prior to study entry
Exclusion criteria
* History of clinical manifestation of any flavivirus infection * History of vaccination against Japanese encephalitis (JE), Yellow fever and Dengue fever (an anti-JEV neutralizing antibody titer \>= 1:10 at baseline is acceptable for inclusion, these subjects will be part of the safety population, but will not be analyzed for immunogenicity in the per-protocol analysis) * Use of any other investigational or non-registered drug or vaccine in addition to the study vaccine during the study period or within 30 days preceding the first dose of study vaccine * Immunodeficiency including post-organ-transplantation or immunosuppressive therapy * A family history of congenital or hereditary immunodeficiency * History of autoimmune disease * Any acute infections within 4 weeks prior to enrollment * Infection with HIV, Hepatitis B or Hepatitis C * Pregnancy, lactation or unreliable contraception in female subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SCR (Seroconversion Rate)of IC51 Compared to JE-VAX at Day 56 | Day 56 | SCR: anti-JEV neutralizing antibody titer ≥1:10 |
| GMT (Geometric Mean Titer) of IC51 Compared to JE-VAX at Day 56 | Day 56 | GMT: geometric mean of PRNT50 |
Secondary
| Measure | Time frame |
|---|---|
| Safety and Adverse Events | until Day 56 |
| Immunogenicity at Day 28 | Day 28 |
| Immunogenicity at Day 56 for North America vs. Europe | Day 56 |
| Immunogenicity at Day 56 for Subjects Older vs. Younger Than 50 Years of Age | Day 56 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IC51 IC51 | 430 |
| JE-VAX JE-VAX | 437 |
| Total | 867 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | administrative reasons | 9 | 11 |
| Overall Study | Adverse Event | 6 | 6 |
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Protocol Violation | 2 | 8 |
| Overall Study | Withdrawal by Subject | 9 | 10 |
Baseline characteristics
| Characteristic | JE-VAX | Total | IC51 |
|---|---|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 14.4 | 41.3 years STANDARD_DEVIATION 14.4 | 41.6 years STANDARD_DEVIATION 14.5 |
| Region of Enrollment Europe | 103 participants | 203 participants | 100 participants |
| Region of Enrollment North America | 334 participants | 664 participants | 330 participants |
| Sex/Gender, Customized Female | 258 participants | 525 participants | 267 participants |
| Sex/Gender, Customized Male | 177 participants | 338 participants | 161 participants |
| Sex/Gender, Customized Unknown | 2 participants | 4 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 217 / 428 | 213 / 435 |
| serious Total, serious adverse events | 1 / 428 | 0 / 435 |
Outcome results
Primary
GMT (Geometric Mean Titer) of IC51 Compared to JE-VAX at Day 56
GMT: geometric mean of PRNT50
Time frame: Day 56
Population: PP Population: All randomized subjects without any major protocol deviations as assessed during a Data Review Meeting. Subjects who were randomized incorrectly or took the wrong study medications were also excluded.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| IC51 | GMT (Geometric Mean Titer) of IC51 Compared to JE-VAX at Day 56 | 243.6 titers | Standard Deviation 1163.1 |
| JE-VAX | GMT (Geometric Mean Titer) of IC51 Compared to JE-VAX at Day 56 | 102 titers | Standard Deviation 221 |
Primary
SCR (Seroconversion Rate)of IC51 Compared to JE-VAX at Day 56
SCR: anti-JEV neutralizing antibody titer ≥1:10
Time frame: Day 56
Population: Per Protocol Population: all randomized subjects without any protocol deviations as defined in the Statistical Analysis Plan
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IC51 | SCR (Seroconversion Rate)of IC51 Compared to JE-VAX at Day 56 | 96.4 percentage of participants |
| JE-VAX | SCR (Seroconversion Rate)of IC51 Compared to JE-VAX at Day 56 | 93.6 percentage of participants |
Secondary
Immunogenicity at Day 28
Time frame: Day 28
Secondary
Immunogenicity at Day 56 for North America vs. Europe
Time frame: Day 56
Secondary
Immunogenicity at Day 56 for Subjects Older vs. Younger Than 50 Years of Age
Time frame: Day 56
Secondary
Safety and Adverse Events
Time frame: until Day 56