Japanese Encephalitis
Conditions
Brief summary
The objective is to investigate the immunogenicity of the Japanese Encephalitis vaccine IC51 (JE-PIV) single and concomitant with HAVRIX® 1440
Detailed description
This is a randomized, controlled, multi-center, single-blind phase 3 study. The study population consists of male and female healthy subjects, aged at least 18 years. 192 subjects will be enrolled at 2 sites in Europe.
Interventions
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 * In female subjects either childbearing potential terminated by surgery or one year post-menopausal, or a negative serum pregnancy test during screening and the willingness not to become pregnant during the study period and 30 days after the last vaccination by practicing reliable methods of contraception * 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) * History of any previous Hepatitis A vaccination and infection * 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 * Planned administration of another vaccine during the study period * Immunodeficiency including post-organ-transplantation or immunosuppressive therapy * A family history of congenital or hereditary immunodeficiency * History of autoimmune disease * Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. * Any acute infections within 4 weeks prior to enrollment * Infection with human immunodeficiency virus (HIV), Hepatitis B (HBsAg) or Hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) at Day 56 for Anti-JEV Neutralizing Antibodies | Day 56 | anti-JEV Neutralizing Antibodies were tabulated for IC51 groups only; for HAV GMTs (co-primary endpoint GMT for Hepatitis A Virus (HAV) Antibody at Day 28), please refer to Outcome 2 within outcome measure section |
| GMT for Hepatitis A Virus (HAV) Antibody at Day 28 | Day 28 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Rate (SCR) at Day 56 for Plaque Reduction Neutralization Assay (PRNT) and HAV at Day 28 | day 28 and 56 | — |
| GMT and SCR for PRNT at Day 28 and HAV at Day 56 | day 28 and 56 | — |
| Safety | until 6 month after last vaccination | Rate of Adverse Events (AEs), Serious Adverse Events (SAEs) and medically attended AEs, local and systemic tolerability, changes in safety laboratory parameters (hematology, serum chemistry, urinalysis) |
Participant flow
Recruitment details
First Subject In: 26.09.2005, Last Subject Out: 14.07.2006 performed at centers for travelling medicine/vaccinology
Participants by arm
| Arm | Count |
|---|---|
| IC51 and Placebo 6 mcg i.m. IC51 with 2 injections (day 0 and 28)and placebo 0.5 mL with 1 injection (day 0) | 65 |
| HAVRIX and Placebo HAVRIX with 1 injection (day 0) and placebo 0.5 mL with 2 injections (day 0 and 28) | 65 |
| IC51 and HAVRIX IC51 6 mcg i.m. with 2 injections (day 0 and 28) and HAVRIX with 1 injection (day 0) | 62 |
| Total | 192 |
Baseline characteristics
| Characteristic | HAVRIX and Placebo | IC51 and Placebo | IC51 and HAVRIX | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 65 Participants | 62 Participants | 192 Participants |
| Region of Enrollment Europe | 65 participants | 65 participants | 62 participants | 192 participants |
| Sex: Female, Male Female | 35 Participants | 34 Participants | 34 Participants | 103 Participants |
| Sex: Female, Male Male | 30 Participants | 31 Participants | 28 Participants | 89 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 | 27 / 65 | 31 / 65 | 24 / 62 |
| serious Total, serious adverse events | 1 / 65 | 0 / 65 | 0 / 62 |
Outcome results
Primary
Geometric Mean Titer (GMT) at Day 56 for Anti-JEV Neutralizing Antibodies
anti-JEV Neutralizing Antibodies were tabulated for IC51 groups only; for HAV GMTs (co-primary endpoint GMT for Hepatitis A Virus (HAV) Antibody at Day 28), please refer to Outcome 2 within outcome measure section
Time frame: Day 56
Population: Per Protocol Population includes all randomized subjects without major protocol deviations
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IC51 and Placebo | Geometric Mean Titer (GMT) at Day 56 for Anti-JEV Neutralizing Antibodies | 192.2 titers |
| IC51 and HAVRIX | Geometric Mean Titer (GMT) at Day 56 for Anti-JEV Neutralizing Antibodies | 202.7 titers |
Comparison: The primary efficacy analysis will compare the IC51+HAVRIX vs. IC51+Placebo group in terms of the GMT for anti- JEV neutralizing antibody at day 56. An observed cases approach will be applied for the primary analysisp-value: <0.0001ANOVA
Primary
GMT for Hepatitis A Virus (HAV) Antibody at Day 28
Time frame: Day 28
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| IC51 and Placebo | GMT for Hepatitis A Virus (HAV) Antibody at Day 28 | 21.7 titers |
| IC51 and HAVRIX | GMT for Hepatitis A Virus (HAV) Antibody at Day 28 | 24 titers |
Comparison: The primary efficacy analysis will compare the IC51+HAVRIX vs. HAVRIX+Placebo group in terms of the GMT for HAV antibody at day 28. An observed cases approach will be applied for the primary analysis.p-value: <0.0001ANOVA
Secondary
GMT and SCR for PRNT at Day 28 and HAV at Day 56
Time frame: day 28 and 56
Secondary
Safety
Rate of Adverse Events (AEs), Serious Adverse Events (SAEs) and medically attended AEs, local and systemic tolerability, changes in safety laboratory parameters (hematology, serum chemistry, urinalysis)
Time frame: until 6 month after last vaccination
Secondary
Seroconversion Rate (SCR) at Day 56 for Plaque Reduction Neutralization Assay (PRNT) and HAV at Day 28
Time frame: day 28 and 56