A Study of ChimeriVax™-JE Live Attenuated Vaccine in Healthy Adults
Condition: Encephalitis; Japanese Encephalitis
MeSH terms: Encephalitis, Japanese; Encephalitis
Intervention: Live attenuated Japanese encephalitis virus, then ChimeriVax diluent; ChimeriVax diluent, then Live attenuated Japanese encephalitis virus
Intervention description: ChimeriVax™-JE, 0.5 mL subcutaneous on Day 0; ChimeriVax diluent 0.5 mL subcutaneous on Day 28; ChimeriVax diluent, 0.5 mL subcutaneous on Day 0 and ChimeriVax™-JE, 0.5 mL subcutaneous on Day 28.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Maximum age: 54 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Japanese Encephalitis; Japanese Encephalitis Vaccines; Adult

Summary:

      The purpose of this study is to assess the safety, tolerability, immunogenicity, and duration
      of immunity of one or two doses of ChimeriVax™-JE vaccine separated by 5 or 6 months in
      adults.

      Objectives:

      Safety:

        -  Obtain safety and tolerability data of a single, fixed dose of ChimeriVax™-JE compared
           with a placebo in adult volunteers (≥ 18 to <55 years) without prior Japanese
           encephalitis (JE) vaccination.

      Immunogenicity:

        -  Obtain data on the antibody response in adult volunteers following administration of
           ChimeriVax™-JE

        -  Assess the durability of the immune response in adult volunteers over 60 months
           following one or two doses of ChimeriVax™-JE.
    

Eligibility criteria:

        Inclusion Criteria :

        At entry:

          -  All aspects of the protocol explained and written informed consent obtained from the
             subject.

          -  Aged ≥ 18 to < 55 years.

          -  In good general health, without significant medical history, physical examination
             findings, or clinically significant abnormal laboratory results.

          -  Subject must be available for the study duration, including all planned follow-up
             visits.

          -  Has the subject agreed 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?

          -  For female subjects of childbearing potential: Negative serum pregnancy tests. An
             efficacious hormonal (i.e., oral, implantable or injectable) or barrier method of
             birth control must be used at least 1 month before Screening and Month 6 and at least
             1 month after Day 28 and Month 6. These subjects will sign an agreement that birth
             control will be practised during the specified periods and will specify the method
             used. Female subjects unable to bear children must have this documented (e.g., tubal
             ligation or hysterectomy).

        For long-term immunogenicity follow-up period:

          -  Subject received an initial dose of ChimeriVax™-JE, has a baseline (Day 0) sample and
             at least one post-vaccination evaluable serological specimen for antibody analysis.

          -  All aspects of the Long-term Immunogenicity Follow-up Period explained and updated
             written informed consent obtained from the subject.

          -  In good general health, without significant medical history that may affect the
             efficacy endpoints or the ability to take blood samples.

        Exclusion Criteria :

          -  A history of vaccination to Japanese encephalitis (JE). Previous vaccination will be
             determined by history (interview of subject) and/or by reviewing the subject's
             vaccination card or other official documentation (either a history of or documentation
             of vaccination fulfils the criterion for exclusion).

          -  Known or suspected immunodeficiency (e.g., human immunodeficiency virus [HIV]
             infection, primary immunodeficiency disorder, leukemia, lymphoma), use of
             immunosuppressive or antineoplastic drugs (corticosteroids > 10 mg prednisone, or
             equivalent, for more than 14 days in the last three months).

          -  Clinically significant abnormalities on laboratory assessment.

          -  Serious adverse reactions characterised by urticaria or angioedema to a prior vaccine.

          -  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 56.

          -  Administration of another vaccine within 30 days preceding the screening visit or up
             to Day 56 (these subjects will be rescheduled for vaccination at a later date).

          -  Physical examination indicating any clinically significant medical condition.

          -  Body temperature >38.1°C (100.6°F) or acute illness within 3 days prior to inoculation
             (subject may be rescheduled).

          -  Intention to travel out of the area prior to the study visit on Day 56.

          -  Seropositive to hepatitis C virus (HCV) or HIV or positive for hepatitis B (HBV)
             (antigen).

          -  Lactation or intended pregnancy in female subjects.

          -  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, ischemia, infection, inflammation of the brain).

        For long-term immunogenicity follow-up period:

          -  History of Yellow Fever or out of study JE vaccination or known flavivirus infection
             since receiving ChimeriVax™-JE vaccination on Day 0 or Day 28 (during double-blind
             treatment period of the study). Yellow Fever/JE vaccination or flavivirus infection
             will be determined by history (interview of subject) and/or by reviewing the subject's
             medical records. Please note subjects who were flavivirus positive at Day 0 will be
             allowed to enrol on the study.

          -  Participation in another JE clinical study.