Japanese Encephalitis
Conditions
Brief summary
The study investigates the long term persistence the Japanese encephalitis vaccine IC51 and the need of a booster dose
Detailed description
This is an open label, non-randomized multi-center phase 3 follow-up study. All volunteers having completed trial IC51-304 (NCT00595790) will be enrolled into this trial at 2 sites
Interventions
BIOLOGICALIC51
Sponsors
Valneva Austria GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
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 * Subjects correctly included in and having completed study IC51-304 according to the protocol.
Exclusion criteria
* Use of any other investigational or non-registered drug or vaccine in addition to the study vaccine during the study period * Immunodeficiency including post-organ-transplantation or immunosuppressive therapy * Pregnancy, lactation or unreliable contraception in female subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination | - 24 months | Seroprotection rate (SPR) (anti-JEV neutralizing antibody titer ≥ 1:10) 24 months (M24) after the primary vaccination - imputed; Persistence of immunogenicity (SPR) at M24 defined as: * pos. (positive) (persistent): Subjects * with a non-missing, pos. seroconversion at D56 (Study IC51-304) and * without booster at M11 or M23 and * with non-missing, seroprotection (SP) pos. PRNT50 at M6 or M12 and * with non-missing, SP pos. PRNT50 at M24 * neg. (negative) (non-persistent): Subjects with * missing or neg. seroconversion at D56 (Study IC51-304) or * booster at M11 or at M23, or * non-missing, SP neg. PRNT50 at M6 or M12 or * missing PRNT50 at both M6 and M12 or * missing or SP neg. PRNT50 (serum dilution giving 50% reduction in plaques in a Plaque Reduction Neutralization Test) at M24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistent and Actual SPR 6, 12 and 24 Months After Primary Vaccination | - 24 months | — |
| Persistent and Actual GMT 6, 12 and 24 Months After Primary Vaccination | 24 months | — |
| SPR 24 Months After the Primary Vaccination (Observed) | 24 months | Persistence of immunogenicity (SPR) at M24 (observed) defined as : * positive (persistent): Subjects * with a non-missing, positive seroconversion at D56 (Study IC51-304), and * who did not receive a booster dose at Visit 2 (M11) or Visit 4 (M23), and * with a non-missing, SP positive PRNT50 result at Visit 1 (M6) or Visit 3 (M12), and * with a non-missing, SP positive PRNT50 result at Visit 5 (M24) * negative (non-persistent): Subjects * with missing or negative seroconversion at D56 (Study IC51-304), or * who did receive a booster dose at Visit 2 (M11) or at Visit 4 (M23), or * with a non-missing, SP negative PRNT50 result at Visit 1 (M6) or Visit 3 (M12), or * with a missing PRNT50 result at both Visit 1 (M6) and Visit 3 (M12), or * with a non-missing, SP negative PRNT50 result at Visit 5 (M24) |
| GMT 1month After Booster Doses | 1 month | — |
| Safety Profile of IC51 | study duration | — |
| SCR 1 Month After the Booster Doses | 1 month | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IC51 2 x 6 µg treatment group in preceeding study IC51-304 | 116 |
| IC51 1 x 12 µg treatment group in preceeding study IC51-304 | 117 |
| IC51 1 x 6 µg treatment group in preceeding study IC51-304 | 116 |
| Total | 349 |
Baseline characteristics
| Characteristic | IC51 2 x 6 µg | IC51 1 x 12 µg | IC51 1 x 6 µg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 9 Participants | 10 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 108 Participants | 106 Participants | 323 Participants |
| Region of Enrollment Europe | 116 participants | 117 participants | 116 participants | 349 participants |
| Sex: Female, Male Female | 67 Participants | 60 Participants | 57 Participants | 184 Participants |
| Sex: Female, Male Male | 49 Participants | 57 Participants | 59 Participants | 165 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 | 61 / 116 | 69 / 117 | 64 / 116 |
| serious Total, serious adverse events | 4 / 116 | 4 / 117 | 3 / 116 |
Outcome results
Primary
Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination
Seroprotection rate (SPR) (anti-JEV neutralizing antibody titer ≥ 1:10) 24 months (M24) after the primary vaccination - imputed; Persistence of immunogenicity (SPR) at M24 defined as: * pos. (positive) (persistent): Subjects * with a non-missing, pos. seroconversion at D56 (Study IC51-304) and * without booster at M11 or M23 and * with non-missing, seroprotection (SP) pos. PRNT50 at M6 or M12 and * with non-missing, SP pos. PRNT50 at M24 * neg. (negative) (non-persistent): Subjects with * missing or neg. seroconversion at D56 (Study IC51-304) or * booster at M11 or at M23, or * non-missing, SP neg. PRNT50 at M6 or M12 or * missing PRNT50 at both M6 and M12 or * missing or SP neg. PRNT50 (serum dilution giving 50% reduction in plaques in a Plaque Reduction Neutralization Test) at M24
Time frame: - 24 months
Population: ITT (Intent-To-Treat) Population: included all subjects rolled over from study IC51-304; analyzed according to treatment to which they were randomized in IC51-304
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IC51 2 x 6 µg | Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination | 56 percentage of participants |
| IC51 1 x 12 µg | Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination | 7 percentage of participants |
| IC51 1 x 6 µg | Long Term Immunogenicity of IC51 Vaccine 24 Months After the Primary Vaccination | 5 percentage of participants |
Secondary
GMT 1month After Booster Doses
Time frame: 1 month
Secondary
Persistent and Actual GMT 6, 12 and 24 Months After Primary Vaccination
Time frame: 24 months
Secondary
Persistent and Actual SPR 6, 12 and 24 Months After Primary Vaccination
Time frame: - 24 months
Secondary
Safety Profile of IC51
Time frame: study duration
Secondary
SCR 1 Month After the Booster Doses
Time frame: 1 month
Secondary
SPR 24 Months After the Primary Vaccination (Observed)
Persistence of immunogenicity (SPR) at M24 (observed) defined as : * positive (persistent): Subjects * with a non-missing, positive seroconversion at D56 (Study IC51-304), and * who did not receive a booster dose at Visit 2 (M11) or Visit 4 (M23), and * with a non-missing, SP positive PRNT50 result at Visit 1 (M6) or Visit 3 (M12), and * with a non-missing, SP positive PRNT50 result at Visit 5 (M24) * negative (non-persistent): Subjects * with missing or negative seroconversion at D56 (Study IC51-304), or * who did receive a booster dose at Visit 2 (M11) or at Visit 4 (M23), or * with a non-missing, SP negative PRNT50 result at Visit 1 (M6) or Visit 3 (M12), or * with a missing PRNT50 result at both Visit 1 (M6) and Visit 3 (M12), or * with a non-missing, SP negative PRNT50 result at Visit 5 (M24)
Time frame: 24 months