Safety and Immunogenicity of ChimeriVax-WN02 West Nile Vaccine in Healthy Adults
Condition: West Nile Fever
MeSH terms: West Nile Fever
Intervention: ChimeriVax-WN02 Low Dose; ChimeriVax-WN02 Medium Dose; ChimeriVax-WN02 High Dose; 0.9% Saline solution; ChimeriVax-WN02 High Dose; 0.9 % NaCl solution
Intervention description: Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region.; Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region; Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region; Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region; Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region; Single dose given in a volume of 0.5 mL by subcutaneous injection to the deltoid region
Intervention MeSH terms: Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 208.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: West Nile Disease; Antibody response; Viremia; Safety; Tolerability; Prevention

Summary:

      The purpose of this study is to determine whether a single subcutaneous injection of
      ChimeriVax-WN02 vaccine is well tolerated, safe and induces protective antibodies against
      West Nile Disease. The study is divided into two parts; in the first part, a comparison of 3
      dose levels of the vaccine will be made, with an inactive control. In the second part, the
      optimum dose level chosen after the first part will be given to older volunteers.
    

Eligibility criteria:

        Inclusion Criteria: Part 1

          -  Healthy adult aged 18 to 40 years.

          -  Women of child-bearing potential should be using hormonal contraception.

          -  Subject had to be available for the study duration, including all planned follow-up
             visits.

        Exclusion Criteria: Part 1

          -  Previous vaccination against yellow fever or Japanese encephalitis

          -  History of flavivirus infection

          -  Any abnormalities of immune system, or using drugs that affect the immune system.

          -  History of anaphylaxis to foods, bee stings, vaccines or drugs.

          -  Receipt of blood or blood products within the preceding 6 months.

          -  Receipt of any vaccine in the preceding 30 days

          -  Seropositive to hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) or Human
             immunodeficiency virus (HIV)

          -  Lactation or intended pregnancy in female subjects

          -  Previous or current military service with overseas deployment

          -  Travel to Mexico or other flavivirus endemic areas in the tropics for periods of four
             weeks or more in the previous ten years.

        Inclusion Criteria: Part 2

          -  Aged ≥ 41 years.

          -  Subjects had to be in general good health.

          -  Unimpaired cognitive performance as assessed by clock drawing test score

          -  Subject had to be available for all required study visits, including all planned
             follow-up visits.

          -  Women of child-bearing potential should be using hormonal contraception.

        Exclusion Criteria: Part 2

          -  Clinically significant abnormalities on the Screening 12-lead electrocardiogram (ECG).

          -  An acute or chronic medical condition that, in the opinion of the Investigator, would
             render vaccination unsafe or would interfere with the evaluation of responses. These
             conditions included, but were not limited to:

               -  History of renal impairment

               -  History of significant liver disease or hepatic impairment

               -  History of diabetes mellitus (except controlled with diet)

               -  An arteriosclerotic event during the 6 months prior to enrollment (including but
                  not limited to myocardial infarction or unstable angina, peripheral bypass
                  surgery for revascularization of an extremity, and transient ischemic attack or
                  stroke)

               -  Signs of congestive heart failure at the time of enrollment

               -  Angina

          -  Subjects with 3 or more of the following:

               -  Age over 50 years

               -  Hypercholesterolemia, or significantly abnormal lipid profile, based on medical
                  history

               -  Any prior history of cardiovascular disease

               -  Significant family history of cardiovascular disease in any immediate relative

               -  History of significant collagen vascular disease.

          -  The unexplained presence of any of the following findings:

               -  Any significant episodes of confusion, memory loss, language impairment, other
                  cognitive impairment, or other abnormal behavior if relatively abrupt in onset

               -  Clinically significant depression

               -  Sudden visual impairment (e.g., loss of vision, double vision)

               -  Slurred or abnormal speech

               -  Sudden onset of vertigo

               -  Focal weakness in any extremity

               -  Focal sensory loss in any extremity

               -  Impaired balance

               -  Impaired gait.

          -  Subjects with any diagnosis of dementia or associated concomitant medications (e.g.,
             Aricept) used for treating dementia.

          -  Subjects with active or a history of neurologic disease or injury, including, but not
             limited to: Parkinson's, Guillain Barre, epilepsy (except febrile seizures in youth
             not treated with medication), cerebrovascular accident, head trauma, or any other
             neurologic condition thought to impact the integrity of the blood-brain barrier.

          -  Subjects taking warfarin, heparin, or with known bleeding disorders.

          -  Relative or employee of the study site staff, CRO, or Sponsor participating in this
             trial.

          -  A history of vaccination against yellow fever (YF) or Japanese encephalitis. Previous
             vaccination was determined by history (interview of subject) and/or by reviewing the
             subject's vaccination card or other official documentation.

          -  History of flavivirus infection (e.g. West Nile [WN], Systemic Lupus Erythematosus
             [SLE], Japanese encephalitis, dengue fever).

          -  History of thymoma, thymic surgery (removal), or myasthenia gravis.

          -  Known or suspected immunodeficiency disorder, including leukemia, lymphoma,
             generalized malignancy, or treatment with immunosuppressive medications, including
             corticosteroids, alkylating agents, anti-metabolites, or radiation therapy. Low dose
             steroids (≤ 10 mg prednisone or equivalent, topical or intra
             articular/bursal/tendon/epidural injections of corticosteroids) did not constitute a
             reason for exclusion.

          -  History of residence in or travel to Mexico or flavivirus endemic areas in the tropics
             (India, southeast Asia, Central America, Caribbean, or South America) for periods of 4
             weeks or more within the last 10 years.

          -  Subjects with clinically significant screening laboratory abnormalities and/or those
             having any of the following:

               -  Compromised hematopoietic function defined as a hemoglobin < 10.9 (males) or 9.4
                  (females) g/dL; lymphocyte count > 3000 mm3; neutrophil count < 1000 mm3; or
                  platelet count < 100,000 mm3.

               -  Hepatic dysfunction defined as a bilirubin above upper limit of normal or
                  aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper
                  limit of normal.

          -  Prior history of anaphylaxis to foods, hymenoptera stings, vaccines, or drugs.

          -  Transfusion of blood or treatment with any blood product, including intramuscular or
             intravenous serum globulin within 6 months of the Screening Visit or anticipated up to
             Day 28, or intention to donate blood in the 28 days after vaccination.

          -  Administration of another vaccine within 30 days preceding the screening visit or
             anticipated up to Day 28 (these subjects could be rescheduled for vaccination at a
             later date).

          -  Physical examination indicating any clinically significant medical condition.

          -  Subjects with body temperature >37.8ºC/100.0ºF or acute illness within 3 days prior to
             vaccination (subject could be rescheduled).

          -  Intention to travel out of the area prior to the study visit on Day 28, such that
             required study visits would be missed.

          -  Seropositive to HCV or HIV or positive for HBsAg.

          -  Participation in another clinical trial within 60 days of Screening.

          -  Lactation or intended pregnancy in female subjects.

          -  History of excessive alcohol consumption, drug abuse, or significant psychiatric
             illness.

          -  Intention to increase normal exercise routine, participate in contact sports or
             strenuous weight lifting, or to initiate vigorous exercise from Screening until after
             Day 28.

          -  At the time of study or past military service with overseas deployment within 10 years
             of screening.