Study of Live Attenuated Japanese Encephalitis Vaccine (ChimeriVax™-JE) and Yellow Fever Vaccine (STAMARIL®)

Study Overview
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Brief Summary
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The purpose of this study is to obtain safety, tolerability, and immunogenicity data on the co-administration or sequential administration of Chimeravax™-JE vaccine and STAMARIL®. Objectives: Safety: Obtain safety and tolerability data of a single, fixed dose of ChimeriVax™-JE administered concurrently, one month before or one month after STAMARIL® to adult volunteers (≥ 18 to ≤ 55 years) without prior Japanese encephalitis (JE) or yellow fever (YF) vaccination. Immunogenicity: Obtain data on the antibody response to a single, fixed dose of ChimeriVax™-JE administered concurrently, one month before or one month after STAMARIL® to adult volunteers without prior JE (or YF) vaccination. Assess the durability of the immune response in adult volunteers 6 months after administration of ChimeriVax™-JE and STAMARIL®.

Detailed Description
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All participants will receive two injections, one to each arm on Days 0 and 30, respectively. Immunogenicity will be tested on Days 0, 15, 30, 45, and 60, and at Month 6.

Official Title
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Randomised, Double-blind, Phase II Evaluation of the Safety and Immunogenicity Following Administration of Live Attenuated JE Vaccine (ChimeriVax™-JE) and Yellow Fever Vaccine (STAMARIL®)

Conditions
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Japanese Encephalitis, Yellow Fever

Intervention / Treatment
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* Biological: Live attenuated Japanese encephalitis virus; Yellow fever virus
* Biological: Yellow fever virus; Live attenuated Japanese encephalitis virus
* Biological: Live attenuated Japanese encephalitis virus; Yellow fever virus
* Biological: Live attenuated Japanese encephalitis virus; Yellow fever virus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : All aspects of the protocol explained and written informed consent obtained from the participant. Aged ≥ 18 to ≤ 55 years at Day 0. In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results. Participant must be available for the study duration, including all planned follow-up visits. The participant must agree to take the following precautions to avoid insect bites for 7 days following vaccination: (a) wear long-sleeved shirts and trousers; (b) apply N,N-Diethyl-meta-toluamide (DEET)-containing insect repellents; (c) sleep in screened enclosures. Female participants of childbearing potential must have a negative serum pregnancy test. An efficacious hormonal method (i.e., oral, implantable or injectable) of contraception or an intrauterine contraceptive device (IUCD) must be used at least 1 month before Screening and at least 1 month after Day 60. These participants will sign an agreement that contraception will be practised during the specified periods and will specify the method used. Female participants unable to become pregnant must have this documented (e.g., tubal ligation or hysterectomy). Exclusion Criteria : A history of flavivirus infection or vaccination to Japanese encephalitis (JE) or yellow fever (YF). Previous vaccination will be determined by history (interview of subject) and/or by reviewing the participant's vaccination card or other official documentation (either a history of or documentation of vaccination fulfils the criterion for exclusion). Impaired immunity, including known or suspected immunodeficiency (e.g., human immunodeficiency virus [HIV] infection, primary immunodeficiency disorder, leukemia, lymphoma), use of immunosuppressive or antineoplastic drugs (including corticosteroids > 10 mg prednisone, or equivalent, for more than 14 days in the last three months). Clinically significant abnormal laboratory assessment results. Serious adverse reactions characterised by urticaria or angioedema to a prior vaccine, chicken or eggs or egg protein. Transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin, within six months of the Screening Visit or up to Day 60. Administration of another vaccine within 28 days of receiving study vaccination. Physical examination indicating any clinically significant medical condition including any short-lived or long-standing illness which has become more severe. Body temperature >38.1°C (100.6°F) or acute illness within 3 days prior to inoculation (participant may be rescheduled). Intention to travel out of the area prior to the study visit on Day 60. Seropositive to hepatitis C virus (HCV) or HIV or positive for hepatitis B virus (HBV) (antigen). Lactation or intended pregnancy in female participants. Excessive alcohol consumption, drug abuse, significant psychiatric illness. A known or suspected physiological or structural condition that compromises the integrity of the blood-brain barrier (e.g., significant hypertensive cerebrovascular disease, trauma, ischaemia, infection, inflammation of the brain).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ChimeriVax™-JE then STAMARIL®<br>Participants will receive ChimeriVax™-JE on Day 0 and STAMARIL® on Day 30 | Biological: Live attenuated Japanese encephalitis virus; Yellow fever virus<br>* ChimeriVax™-JE, 0.5 mL, Subcutaneous on Day 0; STAMARIL®, 0.5 mL, Subcutaneous on Day 30.<br>* Other names: STAMARIL®;|
| Experimental: STAMARIL® then ChimeriVax™-JE<br>Participants will receive STAMARIL® on Day 0 and ChimeriVax™-JE on Day 30 | Biological: Yellow fever virus; Live attenuated Japanese encephalitis virus<br>* STAMARIL®, 0.5 mL Subcutaneous on Day 0; ChimeriVax™-JE, 0.5 mL Subcutaneous on Day 30.<br>* Other names: ChimeriVax™-JE;|
| Experimental: ChimeriVax™-JE and STAMARIL®, then Diluent<br>Participants will receive ChimeriVax™-JE and STAMARIL® on Day 0 and diluent on Day 30. | Biological: Live attenuated Japanese encephalitis virus; Yellow fever virus<br>* ChimeriVax™-JE, 0.5 mL Subcutaneous and STAMARIL®, 0.5 mL, Subcutaneous on Day 0; Diluent 0.5 mL, Subcutaneous on Day 30.<br>* Other names: STAMARIL®;|
| Experimental: Diluent then ChimeriVax™-JE and STAMARIL®<br>Participants will receive Diluent on Day 0 and ChimeriVax™-JE and STAMARIL® on Day 30. | Biological: Live attenuated Japanese encephalitis virus; Yellow fever virus<br>* Diluent, 0.5 mL Subcutaneous on Day 0; ChimeriVax™-JE, 0.5 mL Subcutaneous and STAMARIL®, 0.5 mL Subcutaneous on Day 30.<br>* Other names: STAMARIL®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Japanese Encephalitis Seroconversion Following ChimeriVax™-JE or STAMARIL® Alone or the Co-administration of ChimeriVax™-JE and STAMARIL®, or Placebo Vaccination. | Neutralising antibody titer against homologous Japanese encephalitis (JE), yellow fever (YF), and other relevant wild type JE strains were determined using a 50% serum dilution plaque reduction neutralisation test. Seroconversion post-vaccination was defined as the appearance of neutralising antibody titer when not present at Day 0, or at least a four-fold rise in neutralising antibody titer between the pre-vaccination (Day 0) and the post-vaccination samples. The 30 Days post-JE seroconversion is: Day 30 for Group 1 (ChimeriVax™-JE then STAMARIL®) and Group 3 (Co-administration of ChimeriVax™-JE and STAMARIL, then Diluent); Day 60 for Group 2 (STAMARIL® then ChimeriVax™-JE) and Group 4 (Diluent then Co-administration of ChimeriVax™-JE and STAMARIL). | Pre-vaccination (Day 0 or 30) and post-vaccination (Day 30 or 60) | 
| Number of Participants With Yellow Fever Seroconversion Following ChimeriVax™-JE or STAMARIL® Alone or the Co-administration of ChimeriVax™-JE and STAMARIL® or Placebo Vaccination. | Neutralising antibody titer against yellow fever strains was determined using a 50% serum dilution plaque reduction neutralisation test. Seroconversion at a later post vaccination timepoint ws defined as the appearance of neutralising antibody titer when not present at Day 0, or at least a four-fold rise in neutralising antibody titre between the pre-injection Day 0 and later post vaccination samples. The Day 30 post-JE seroconversion is: Day 30 for Group 1 (ChimeriVax™-JE then STAMARIL®) and Group 3 (Co-administration of ChimeriVax™-JE and STAMARIL, then Diluent); Day 60 for Group 2 (STAMARIL® then ChimeriVax™-JE) and Group 4 (Diluent then Co-administration of ChimeriVax™-JE and STAMARIL). | Pre-vaccination (Day 0 or 30) and post-vaccination (Day 30 or 60) | 
| Number of Participants Who Seroconverted to Japanese Encephalitis 30 Days Post ChimeriVax™-JE Vaccination | Neutralising antibody titer against homologous JE, YF, and other relevant wild type JE strains was determined using a 50% serum dilution plaque reduction neutralisation test. Seroconversion at a later post vaccination timepoint was defined as the appearance of neutralising antibody titer when not present at Day 0, or at least a four-fold rise in neutralising antibody titer between the pre-injection Day 0 and post-vaccination samples. | Day 0 (Pre-vaccination) through Day 30 post-vaccination | 
| Number of Participants Reporting Solicited Local and Systemic Adverse Events Post Vaccination With ChimeriVax™-JE or STAMARIL® Alone or the Co-Administration of ChimeriVax™-JE and STAMARIL®, or Placebo | Solicited Local Adverse Events: Injection Site Pain, Erythema, Swelling, Hemorrhage, Venipuncture site Hemorrhage. Solicited Systemic Adverse Events: Fatigue, Malaise, Pyrexia, Chills, Headache, Dizziness, Myalgia, Abdominal Pain, Diarrhea, Nausea, Pharyngolaryngeal Pain. All solicited local reactions associated with ChimeriVax™-JE are presented in Group 1, those associated with STAMARIL® in Group 2, those associated with co-administered vaccines in Group 3, and those associated with diluent in Group 4. The solicited systemic adverse events are reported according to the participants' randomized study groups. | Day 0 up to Day 60 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) to Japanese Encephalitis (Homologous Virus) Following ChimeriVax™-JE or STAMARIL® Alone or the Co-administration of ChimeriVax™-JE and STAMARIL®, or Placebo Vaccination. | Neutralising antibody titer against homologous Japanese encephalitis (JE) and other relevant wild type JE strains was determined using a 50% serum dilution plaque reduction neutralisation test. Post-vaccination 15 (30) Days JE seroconversion is: Day 15 (30) for Group 1 (ChimeriVax™-JE then STAMARIL®) and Group 3 (Co-administration of ChimeriVax™-JE and STAMARIL, then Diluent); Day 45 (60) for Group 2 (STAMARIL® then ChimeriVax™-JE) and Group 4 (Diluent then Co-administration of ChimeriVax™-JE and STAMARIL) | Day 0 through 6 months post-vaccination | 
| Geometric Mean Titers to Yellow Fever (Homologous Virus) Following ChimeriVax™-JE or STAMARIL® Alone or the Co-administration of ChimeriVax™-JE and STAMARIL®, or Placebo | Neutralising antibody titer against homologous yellow fever was determined using a 50% serum dilution plaque reduction neutralisation test. Post vaccination 15 (30) Days Yellow Fever seroconversion is: Day 15 (30) for Group 1 (ChimeriVax™-JE then STAMARIL®) and Group 3 (Co-administration of ChimeriVax™-JE and STAMARIL, then Diluent); Day 45 (60) for Group 2 (STAMARIL® then ChimeriVax™-JE) and Group 4 (Diluent then Co-administration of ChimeriVax™-JE and STAMARIL). | Day 0 through 6 months post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese Encephalitis, Yellow Fever, ChimeriVax™-JE, STAMARIL®, Adult