Encephalitis
Conditions
Keywords
Pediatric, Japanese Encephalitis Vaccine, non-endemic countries, to assess immunogenicity of purified inactivated Japanese Encephalitis (JE) vaccine IC51
Brief summary
The primary objective is to assess the safety profile of IC51 in a pediatric population from regions where JEV is not endemic
Interventions
BIOLOGICALIC51
0.25 ml, 2 i.m. vaccinations at Day 0 and 28
Sponsors
Valneva Austria GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 17 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. * The subject is planning to travel to an area where JE is endemic after completion of the vaccination schedule. Exposure to JE should be avoided until 1 week after the second IC51 dose and subjects should return from travel to JE endemic areas before the Month 7 visit. The planned travel to JE endemic areas should not interfere with the study visits and can take place between Visit 2 + 7 days to Month 7.
Exclusion criteria
* Clinical manifestation or history of any Flavivirus disease * Vaccination against JE (except within this protocol), Yellow fever, West Nile virus and Dengue at any time prior or during the study * 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 1 week before and 1 week after each IC51 vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Day 56 After the First Vaccination | until Day 56 | Rate of subjects with serious adverse events (SAEs) and medically attended AEs up to Day 56 after the first vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Subjects With Abnormal Laboratory Parameters up to Day 56 and up to Month 7 After the First Vaccination | up to Month 7 | Laboratory parameters were assessed at the Day 28, Day 56 and Month 7 visit. Endpoint reflects abnormal laboratory parameters assessed as clinically significant by the investigator. |
| Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Month 7 After the First Vaccination | up to Month 7 | — |
| Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | 7 days | — |
| Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 After the First Vaccination | up to Day 56 and upt to Month 7 | — |
| GMTs for JEV Neutralizing Antibodies Measured Using a Validated PRNT at Day 56 and Month 7 | at Day 56 and Month 7 | — |
| SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | at Day 56 and Month 7 | — |
| GMTs at Day 56 and Month 7 Stratified According to Age Groups | at Day 56 and Month 7 | — |
| SCRs as Defined as Percentage of Subjects With JEV Neutralizing Antibody Titers of PRNT 50 >= 1:10 at Day 56 and Month 7, Measured Using a Validated Plaque Reduction Neutralization Test (PRNT) | at Day 56 and Month 7 | — |
Countries
Australia, Denmark, Germany, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| >=2 Months to <3 Years IC51 0.25 ml, 2 i.m.vaccinations at Day 0 and Day 28 | 12 |
| >=3 to <12 Years IC51, 0.5 ml, 2 i.m. vaccinations at Day 0 and 28 | 29 |
| >=12 to <18 Years IC51, 0.5 ml, 2 i.m. vaccinations at Day 0 and 28 | 59 |
| Total | 100 |
Baseline characteristics
| Characteristic | >=2 Months to <3 Years | >=3 to <12 Years | >=12 to <18 Years | Total |
|---|---|---|---|---|
| Age, Continuous | 1.81 years STANDARD_DEVIATION 0.811 | 6.98 years STANDARD_DEVIATION 2.417 | 15.90 years STANDARD_DEVIATION 1.176 | 11.62 years STANDARD_DEVIATION 5.605 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 22 Participants | 53 Participants | 83 Participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 36 Participants | 53 Participants |
| Sex: Female, Male Male | 7 Participants | 17 Participants | 23 Participants | 47 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 | 11 / 12 | 22 / 29 | 49 / 59 |
| serious Total, serious adverse events | 0 / 12 | 0 / 29 | 3 / 59 |
Outcome results
Primary
Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Day 56 After the First Vaccination
Rate of subjects with serious adverse events (SAEs) and medically attended AEs up to Day 56 after the first vaccination.
Time frame: until Day 56
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| >=2 Months to <3 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Day 56 After the First Vaccination | 33.3 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Day 56 After the First Vaccination | 20.7 percentage of participants |
| >=12 to <18 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Day 56 After the First Vaccination | 3.4 percentage of participants |
Secondary
GMTs at Day 56 and Month 7 Stratified According to Age Groups
Time frame: at Day 56 and Month 7
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| >=2 Months to <3 Years | GMTs at Day 56 and Month 7 Stratified According to Age Groups | GMT Day 56 | 216.18 Titer |
| >=2 Months to <3 Years | GMTs at Day 56 and Month 7 Stratified According to Age Groups | GMT Month 7 | 47.96 Titer |
| >=3 to <12 Years | GMTs at Day 56 and Month 7 Stratified According to Age Groups | GMT Day 56 | 508.03 Titer |
| >=3 to <12 Years | GMTs at Day 56 and Month 7 Stratified According to Age Groups | GMT Month 7 | 31.96 Titer |
| >=12 to <18 Years | GMTs at Day 56 and Month 7 Stratified According to Age Groups | GMT Day 56 | 295.44 Titer |
| >=12 to <18 Years | GMTs at Day 56 and Month 7 Stratified According to Age Groups | GMT Month 7 | 60.65 Titer |
Secondary
GMTs for JEV Neutralizing Antibodies Measured Using a Validated PRNT at Day 56 and Month 7
Time frame: at Day 56 and Month 7
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| >=2 Months to <3 Years | GMTs for JEV Neutralizing Antibodies Measured Using a Validated PRNT at Day 56 and Month 7 | GMT Day 56 | 216.18 Titer |
| >=2 Months to <3 Years | GMTs for JEV Neutralizing Antibodies Measured Using a Validated PRNT at Day 56 and Month 7 | GMT Month 7 | 47.96 Titer |
| >=3 to <12 Years | GMTs for JEV Neutralizing Antibodies Measured Using a Validated PRNT at Day 56 and Month 7 | GMT Day 56 | 340.74 Titer |
| >=3 to <12 Years | GMTs for JEV Neutralizing Antibodies Measured Using a Validated PRNT at Day 56 and Month 7 | GMT Month 7 | 57.12 Titer |
Secondary
Rate of Subjects With Abnormal Laboratory Parameters up to Day 56 and up to Month 7 After the First Vaccination
Laboratory parameters were assessed at the Day 28, Day 56 and Month 7 visit. Endpoint reflects abnormal laboratory parameters assessed as clinically significant by the investigator.
Time frame: up to Month 7
Population: not from all subjects samples were collected, Overall number of participants analyzed were number of participants at Day 0
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| >=2 Months to <3 Years | Rate of Subjects With Abnormal Laboratory Parameters up to Day 56 and up to Month 7 After the First Vaccination | White Blood cells on Day 28 | 1 Participants |
| >=2 Months to <3 Years | Rate of Subjects With Abnormal Laboratory Parameters up to Day 56 and up to Month 7 After the First Vaccination | Platelets on Day 28 | 0 Participants |
| >=3 to <12 Years | Rate of Subjects With Abnormal Laboratory Parameters up to Day 56 and up to Month 7 After the First Vaccination | White Blood cells on Day 28 | 0 Participants |
| >=3 to <12 Years | Rate of Subjects With Abnormal Laboratory Parameters up to Day 56 and up to Month 7 After the First Vaccination | Platelets on Day 28 | 1 Participants |
Secondary
Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Month 7 After the First Vaccination
Time frame: up to Month 7
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=2 Months to <3 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Month 7 After the First Vaccination | SAEs | 0 percentage of participants |
| >=2 Months to <3 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Month 7 After the First Vaccination | medically attended AEs | 33.3 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Month 7 After the First Vaccination | SAEs | 3.4 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Serious Adverse Events (SAEs) and Medically Attended AEs up to Month 7 After the First Vaccination | medically attended AEs | 18.2 percentage of participants |
Secondary
Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination
Time frame: 7 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=2 Months to <3 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Local after 1st Vaccination | 28.6 percentage of participants |
| >=2 Months to <3 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Systemic after 1st Vaccination | 33.3 percentage of participants |
| >=2 Months to <3 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Local after 2nd Vaccination | 22.2 percentage of participants |
| >=2 Months to <3 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Systemic after 2nd Vaccination | 28.6 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Systemic after 2nd Vaccination | 22.6 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Local after 1st Vaccination | 48.9 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Local after 2nd Vaccination | 29.4 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Solicited Local and Systemic aEs Assessed With a Subject Diary for 7 Consecutive Days After Each Vaccination | any Systemic after 1st Vaccination | 46.0 percentage of participants |
Secondary
Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 After the First Vaccination
Time frame: up to Day 56 and upt to Month 7
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=2 Months to <3 Years | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 After the First Vaccination | any unsolicited AE up to Day 56 | 83.3 percentage of participants |
| >=2 Months to <3 Years | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 After the First Vaccination | any unsolicited AE up to Month 7 | 91.7 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 After the First Vaccination | any unsolicited AE up to Day 56 | 29.5 percentage of participants |
| >=3 to <12 Years | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 After the First Vaccination | any unsolicited AE up to Month 7 | 43.2 percentage of participants |
Secondary
SCRs as Defined as Percentage of Subjects With JEV Neutralizing Antibody Titers of PRNT 50 >= 1:10 at Day 56 and Month 7, Measured Using a Validated Plaque Reduction Neutralization Test (PRNT)
Time frame: at Day 56 and Month 7
Population: number analyzed = number of subjects achieving seroconversion Overall number of participants analyzed were number of participants at Day 0
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=2 Months to <3 Years | SCRs as Defined as Percentage of Subjects With JEV Neutralizing Antibody Titers of PRNT 50 >= 1:10 at Day 56 and Month 7, Measured Using a Validated Plaque Reduction Neutralization Test (PRNT) | SCR Day 56 | 100.0 percentage of participants |
| >=2 Months to <3 Years | SCRs as Defined as Percentage of Subjects With JEV Neutralizing Antibody Titers of PRNT 50 >= 1:10 at Day 56 and Month 7, Measured Using a Validated Plaque Reduction Neutralization Test (PRNT) | SCR Month 7 | 100.0 percentage of participants |
| >=3 to <12 Years | SCRs as Defined as Percentage of Subjects With JEV Neutralizing Antibody Titers of PRNT 50 >= 1:10 at Day 56 and Month 7, Measured Using a Validated Plaque Reduction Neutralization Test (PRNT) | SCR Day 56 | 100.0 percentage of participants |
| >=3 to <12 Years | SCRs as Defined as Percentage of Subjects With JEV Neutralizing Antibody Titers of PRNT 50 >= 1:10 at Day 56 and Month 7, Measured Using a Validated Plaque Reduction Neutralization Test (PRNT) | SCR Month 7 | 90.6 percentage of participants |
Secondary
SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups
Time frame: at Day 56 and Month 7
Population: number analyzed = number of subjects achieving seroconversion Overall number of participants analyzed were number of participants at Day 0
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| >=2 Months to <3 Years | SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | SCR Day 56 | 100 percentage of participants |
| >=2 Months to <3 Years | SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | SCR Month 7 | 100.0 percentage of participants |
| >=3 to <12 Years | SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | SCR Day 56 | 100.0 percentage of participants |
| >=3 to <12 Years | SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | SCR Month 7 | 66.7 percentage of participants |
| >=12 to <18 Years | SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | SCR Day 56 | 100.0 percentage of participants |
| >=12 to <18 Years | SCRs at Day 56 and Month 7 Stratified According to Dose Groups and Age Groups | SCR Month 7 | 93.1 percentage of participants |