Study of a Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV™) Compared to CD.JEVAX™ in Toddlers
Study Details
Study Description
Brief Summary
The purpose of this study is to compare Live Attenuated Japanese Encephalitis Chimeric Virus Vaccine (IMOJEV™) with Japanese encephalitis live attenuated vaccine (SA14 14 2 vaccine [CD.JEVAX™]) after a single dose vaccination to support product registration.
Primary Objective:
- To demonstrate the non-inferiority of the antibody response 28 days after administration of one dose of IMOJEV™ compared to the antibody response 28 days after administration of one dose of the CD.JEVAX™ control vaccine.
Secondary Objectives:
-
To describe the immune response to Japanese encephalitis (JE) in both vaccine groups using 50% plaque reduction neutralization assay (PRNT50) assays before and after a single dose of IMOJEV™ vaccine or a single dose of CD.JEVAX™ vaccine.
-
To describe the safety of vaccination in all subjects up to 28 days and all serious adverse events up to 6-month after vaccination.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
All participants will receive a single dose of their assigned vaccination at Visit 1 (Day 0) and undergo immunogenicity assessment at Day 28 post-vaccination. Safety will be assessed from day of vaccination and up to 6 months post-vaccination.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IMOJEV™ Vaccine Group Participants will receive a single dose of the Live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV™) on Day 0. |
Biological: Live attenuated Japanese encephalitis chimeric virus vaccine
0.5 mL, Subcutaneous
Other Names:
|
| Active Comparator: CD.JEVAX ™ Vaccine Group Participants will receive a single dose of the Japanese encephalitis live attenuated vaccine (SA14 14 2 vaccine), CD.JEVAX™ on Day 0 |
Biological: Japanese encephalitis live attenuated vaccine (SA14 14 2 vaccine)
0.5 mL, Subcutaneous
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Seroconversion to Japanese Encephalitis Chimeric Virus Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine [Day 28 post-vaccination]
Immunogenicity assessed using a Japanese encephalitis chimeric virus (JE-CV) 50% Plaque Reduction Neutralization Test (PRNT50). Seroconversion was defined as the percentage of participants who developed neutralizing antibody titers above 10 (1/dil) when seronegative at baseline (<1/10) or who presented a ≥4-fold rise in their neutralizing antibody titers when seropositive (≥1/10) at baseline.
Secondary Outcome Measures
- Geometric Mean Titers Against the Japanese Encephalitis Chimeric Virus Before And Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine [Day 0 (pre-vaccination) and Day 28 post-vaccination]
Geometric mean titers were assessed using a Japanese encephalitis chimeric virus (JE-CV) 50% Plaque Reduction Neutralization Test (PRNT50). JE-CV PRNT50 antibody titer >10 (1/dil, Day 0)
- Number of Participants With Seroprotection Against Japanese Encephalitis Chimeric Virus Before And Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine [Day 0 (pre-vaccination) and Day 28 post-vaccination]
Immunogenicity was assessed using a Japanese encephalitis chimeric virus (JE-CV) PRNT50 assay. Seroprotection was defined as the percentage of participants with a titer ≥10 (1/dil) at pre-vaccination and at Day 28 post-vaccination.
- Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine [Day 0 up to Day 14 post-vaccination]
Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Loss, and Irritability. Grade 3 injection site: Pain - Cries when injected limb is moved or the movement of injected limb is reduced; Erythema and Swelling longest diameter ≥50 mm. Grade 3 systemic reactions: Fever >39.5°C; Vomiting ≥6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal - >3 hours; Drowsiness - sleeping most of the time or difficult to wake; Appetite Loss - refuses ≥3 feeds or most feeds; Irritability - inconsolable.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged 12 to 24 months on the day of inclusion
-
In good general health, without significant medical history.
-
Provision of informed consent form signed by at least one parent or other legally acceptable representative.
-
Subject and parent/guardian able to attend all scheduled visits and comply with all trial procedures.
Exclusion Criteria:
-
Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the trial vaccination.
-
Planned participation in another clinical trial during the present trial period.
-
Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy.
-
Known systemic hypersensitivity to any of IMOJEV™ components or history of a life-threatening reaction to a vaccine containing any of the same substances and vaccination,known systemic hypersensitivity to CD.JEVAX® main components and the other components (including Gelatin, kanamycin, and gentamicin).
-
Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
-
Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of the immune response.
-
Previous vaccination against flavivirus disease, including Japanese encephalitis (JE).
-
Administration of any anti-viral within 2 months preceding Visit 01 and up to the 4 weeks following the trial vaccination.
-
Receipt of any vaccine in the 4 weeks preceding the first trial vaccination, except for pandemic influenza vaccination, which may be received at least two weeks before the study vaccines.
-
Planned receipt of any vaccine from the inclusion up to the 4 weeks following the trial vaccination.
-
History of central nervous system disorder or disease, including seizures.
-
Planned receipt of any JE vaccine during the course of the study.
-
History of flavivirus infection (confirmed either clinically, serologically or virologically).
-
Administration of systemic corticosteroids for more than two consecutive weeks within the 4 weeks preceding vaccination.
-
Febrile illness (temperature ≥38.0°C) or moderate or severe acute illness/infection 3 days before vaccination as well as the day of vaccination, according to Investigator judgment.
-
Thrombocytopenia or bleeding disorder contraindicated for vaccination with same administration route, or receipt of anticoagulants in the 3 weeks preceding inclusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Goyang | Korea, Republic of | |||
| 2 | Incheon | Korea, Republic of | |||
| 3 | Seongnam | Korea, Republic of | |||
| 4 | Seoul | Korea, Republic of | |||
| 5 | Suwon | Korea, Republic of | |||
| 6 | Wonju | Korea, Republic of |
Sponsors and Collaborators
- Sanofi Pasteur, a Sanofi Company
Investigators
- Study Director: Medical Director, Sanofi Pasteur SA
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- JEC12
- U1111-1117-7378
Study Results
Participant Flow
| Recruitment Details | The study participants were enrolled from 12 July 2011 to 28 September 2012 at 10 clinic centers in South Korea. |
|---|---|
| Pre-assignment Detail | A total of 274 participants who met all of the inclusion and none of the exclusion criteria were randomized and vaccinated in this study. |
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group |
|---|---|---|
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ |
| Period Title: Overall Study | ||
| STARTED | 137 | 137 |
| COMPLETED | 137 | 136 |
| NOT COMPLETED | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group | Total |
|---|---|---|---|
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ | Total of all reporting groups |
| Overall Participants | 137 | 137 | 274 |
| Age (Count of Participants) | |||
| <=18 years |
137
100%
|
137
100%
|
274
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (Months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Months] |
14.0
(2.0)
|
14.3
(2.2)
|
14.2
(2.1)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
58
42.3%
|
57
41.6%
|
115
42%
|
| Male |
79
57.7%
|
80
58.4%
|
159
58%
|
| Region of Enrollment (Number) [Number] | |||
| South Korea |
137
100%
|
137
100%
|
274
100%
|
Outcome Measures
| Title | Percentage of Participants With Seroconversion to Japanese Encephalitis Chimeric Virus Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine |
|---|---|
| Description | Immunogenicity assessed using a Japanese encephalitis chimeric virus (JE-CV) 50% Plaque Reduction Neutralization Test (PRNT50). Seroconversion was defined as the percentage of participants who developed neutralizing antibody titers above 10 (1/dil) when seronegative at baseline (<1/10) or who presented a ≥4-fold rise in their neutralizing antibody titers when seropositive (≥1/10) at baseline. |
| Time Frame | Day 28 post-vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Seroconversion to JE-CV was assessed in the Per-Protocol Analysis Set. |
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group |
|---|---|---|
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ |
| Measure Participants | 119 | 117 |
| Number [Percentage of Participants] |
100
73%
|
99.1
72.3%
|
| Title | Geometric Mean Titers Against the Japanese Encephalitis Chimeric Virus Before And Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine |
|---|---|
| Description | Geometric mean titers were assessed using a Japanese encephalitis chimeric virus (JE-CV) 50% Plaque Reduction Neutralization Test (PRNT50). JE-CV PRNT50 antibody titer >10 (1/dil, Day 0) |
| Time Frame | Day 0 (pre-vaccination) and Day 28 post-vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Geometric mean titers against the JE-CV was assessed in the Per-Protocol Analysis Set. |
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group |
|---|---|---|
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ |
| Measure Participants | 119 | 117 |
| JE-CV PRNT50 antibody titer (pre-vaccination) |
5.0
|
5.0
|
| JE-CV PRNT50 antibody titer (post-vaccination) |
908
|
579
|
| Title | Number of Participants With Seroprotection Against Japanese Encephalitis Chimeric Virus Before And Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine |
|---|---|
| Description | Immunogenicity was assessed using a Japanese encephalitis chimeric virus (JE-CV) PRNT50 assay. Seroprotection was defined as the percentage of participants with a titer ≥10 (1/dil) at pre-vaccination and at Day 28 post-vaccination. |
| Time Frame | Day 0 (pre-vaccination) and Day 28 post-vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Seroprotection against JE-CV was assessed in the Per-Protocol Analysis Set. |
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group |
|---|---|---|
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ |
| Measure Participants | 119 | 117 |
| JE-CV PRNT50 antibody titer ≥10 (1/dil, Day 0) |
0
0%
|
0
0%
|
| JE-CV PRNT50 antibody titer ≥10 (1/dil, Day 28) |
119
86.9%
|
116
84.7%
|
| Title | Number of Participants Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Either IMOJEV™ or CD.JEVAX™ Japanese Encephalitis Vaccine |
|---|---|
| Description | Solicited injection site: Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite Loss, and Irritability. Grade 3 injection site: Pain - Cries when injected limb is moved or the movement of injected limb is reduced; Erythema and Swelling longest diameter ≥50 mm. Grade 3 systemic reactions: Fever >39.5°C; Vomiting ≥6 episodes per 24 hours or requiring parenteral hydration; Crying Abnormal - >3 hours; Drowsiness - sleeping most of the time or difficult to wake; Appetite Loss - refuses ≥3 feeds or most feeds; Irritability - inconsolable. |
| Time Frame | Day 0 up to Day 14 post-vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Solicited injection site reactions and systemic reactions were assessed in the Safety Analysis Set. |
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group |
|---|---|---|
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ |
| Measure Participants | 137 | 137 |
| Injection site Pain (N = 137, 137) |
35
25.5%
|
38
27.7%
|
| Grade 3 Injection site Pain (N = 137, 137) |
0
0%
|
1
0.7%
|
| Injection site Erythema (N = 137, 137) |
23
16.8%
|
33
24.1%
|
| Grade 3 Injection site Erythema (N = 137, 137) |
0
0%
|
0
0%
|
| Injection site Swelling (N = 137, 137) |
6
4.4%
|
10
7.3%
|
| Grade 3 Injection site Swelling (N = 137, 137) |
0
0%
|
0
0%
|
| Fever (N = 134, 136) |
33
24.1%
|
34
24.8%
|
| Grade 3 Fever (N = 134, 136) |
1
0.7%
|
1
0.7%
|
| Vomiting (N = 137, 137) |
9
6.6%
|
14
10.2%
|
| Grade 3 Vomiting (N = 137, 137) |
1
0.7%
|
2
1.5%
|
| Crying Abnormal (N = 137, 137) |
27
19.7%
|
35
25.5%
|
| Grade 3 Crying Abnormal (N = 137, 137) |
2
1.5%
|
3
2.2%
|
| Drowsiness (N = 137, 137) |
23
16.8%
|
33
24.1%
|
| Grade 3 Drowsiness (N = 137, 137) |
0
0%
|
1
0.7%
|
| Appetite Loss (N = 137, 137) |
38
27.7%
|
40
29.2%
|
| Grade 3 Appetite Loss (N = 137, 137) |
4
2.9%
|
1
0.7%
|
| Irritability (N = 137, 137) |
31
22.6%
|
36
26.3%
|
| Grade 3 Irritability (N = 137, 137) |
1
0.7%
|
5
3.6%
|
Adverse Events
| Time Frame | Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 post-vaccination. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group | ||
| Arm/Group Description | Participants age 12 to 24 months received one dose of IMOJEV™ | Participants age 12 to 24 months received one dose of CD.JEVAX™ | ||
All Cause Mortality |
||||
| IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/137 (12.4%) | 18/137 (13.1%) | ||
| Gastrointestinal disorders | ||||
| Intestinal obstruction | 1/137 (0.7%) | 1 | 0/137 (0%) | 0 |
| Intussusception | 1/137 (0.7%) | 1 | 0/137 (0%) | 0 |
| Stomatitis | 0/137 (0%) | 0 | 1/137 (0.7%) | 1 |
| General disorders | ||||
| Pyrexia | 1/137 (0.7%) | 1 | 2/137 (1.5%) | 2 |
| Hepatobiliary disorders | ||||
| Hepatitis | 0/137 (0%) | 0 | 1/137 (0.7%) | 1 |
| Infections and infestations | ||||
| Bronchiolitis | 1/137 (0.7%) | 1 | 1/137 (0.7%) | 1 |
| Bronchitis | 2/137 (1.5%) | 2 | 1/137 (0.7%) | 2 |
| Croup infectious | 0/137 (0%) | 0 | 1/137 (0.7%) | 1 |
| Gastroenteritis | 1/137 (0.7%) | 1 | 3/137 (2.2%) | 3 |
| Hand foot and mouth disease | 0/137 (0%) | 0 | 1/137 (0.7%) | 1 |
| Herpangina | 1/137 (0.7%) | 1 | 0/137 (0%) | 0 |
| Lymph node abscess | 1/137 (0.7%) | 1 | 0/137 (0%) | 0 |
| Meningitis aseptic | 1/137 (0.7%) | 1 | 0/137 (0%) | 0 |
| Pharyngitis | 2/137 (1.5%) | 2 | 1/137 (0.7%) | 1 |
| Pharyngotonsillitis | 1/137 (0.7%) | 1 | 1/137 (0.7%) | 1 |
| Pneumonia | 5/137 (3.6%) | 5 | 3/137 (2.2%) | 3 |
| Urinary tract infection | 0/137 (0%) | 0 | 1/137 (0.7%) | 2 |
| Nervous system disorders | ||||
| Febrile convulsion | 0/137 (0%) | 0 | 1/137 (0.7%) | 1 |
| Kawasaki's disease | 2/137 (1.5%) | 2 | 1/137 (0.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| IMOJEV™ Vaccine Group | CD.JEVAX™ Vaccine Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 74/137 (54%) | 69/137 (50.4%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 9/137 (6.6%) | 9 | 3/137 (2.2%) | 3 |
| Vomiting | 9/137 (6.6%) | 9 | 14/137 (10.2%) | 14 |
| General disorders | ||||
| Pyrexia | 8/137 (5.8%) | 8 | 9/137 (6.6%) | 9 |
| Injection site Pain | 35/137 (25.5%) | 35 | 38/137 (27.7%) | 38 |
| Injection site Erythema | 23/137 (16.8%) | 23 | 33/137 (24.1%) | 33 |
| Injection site Swelling | 6/137 (4.4%) | 6 | 10/137 (7.3%) | 10 |
| Fever | 33/134 (24.6%) | 33 | 34/136 (25%) | 34 |
| Infections and infestations | ||||
| Bronchitis | 9/137 (6.6%) | 9 | 6/137 (4.4%) | 7 |
| Gastroenteritis | 4/137 (2.9%) | 4 | 7/137 (5.1%) | 8 |
| Nasopharyngitis | 42/137 (30.7%) | 54 | 38/137 (27.7%) | 44 |
| Otitis media | 6/137 (4.4%) | 7 | 8/137 (5.8%) | 9 |
| Upper respiratory tract infection | 11/137 (8%) | 13 | 4/137 (2.9%) | 5 |
| Metabolism and nutrition disorders | ||||
| Appetite Loss | 38/137 (27.7%) | 38 | 40/137 (29.2%) | 40 |
| Nervous system disorders | ||||
| Drowsiness | 23/137 (16.8%) | 23 | 33/137 (24.1%) | 33 |
| Psychiatric disorders | ||||
| Crying Abnormal | 27/137 (19.7%) | 27 | 35/137 (25.5%) | 35 |
| Irritability | 31/137 (22.6%) | 31 | 36/137 (26.3%) | 36 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Rhinorrhea | 5/137 (3.6%) | 7 | 7/137 (5.1%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Sanofi Pasteur Inc. |
| Phone | |
| RegistryContactUs@sanofipasteur.com |
- JEC12
- U1111-1117-7378