Safety and Immunogenicity Study of ChimeriVax West Nile Vaccine in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if ChimeriVax West Nile vaccine is safe and effective in preventing West Nile disease in adults over 50 years of age.

Detailed Description
-----------------
Currently, the only method of prevention of West Nile infection is control of the mosquito vectors associated or avoidance of mosquito bites, which has proven largely ineffective. Developing a safe, effective vaccine and making it widely available will enhance the prospects of prevention and control of this disease. In addition, natural infections with the YF virus and WN virus are more severe in the elderly. Therefore, a study among healthy older subjects or those with well controlled chronic diseases will provide data to determine a ChimeriVax-WN02 vaccine dose that is immunogenic and well tolerated.

Official Title
-----------------
Randomized, Modified, Double-blind, Placebo-controlled, Phase II, Dose-ranging Study of the Safety and Immunogenicity of Single Dose ChimeriVax-WN02 Vaccine in Healthy Adults.

Conditions
-----------------
West Nile Fever

Intervention / Treatment
-----------------
* Biological: ChimeriVax-WN02 vaccine
* Biological: ChimeriVax-WN02 vaccine
* Biological: ChimeriVax-WN02 vaccine
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Medically stable, ambulatory male or female ≥ 50 years of age. Attend all scheduled visits and to comply with all study procedures. Negative serum pregnancy test at Screening, and a negative urine pregnancy test on Day 0. Exclusion Criteria: Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 10 mg of prednisone or equivalent), or depot preparation within the previous 3 months. Topical steroids are allowed. Administration of immunoglobulins and/or any blood products within 3 months before enrollment or planned administration during treatment period of study. Presence of acute or chronic illness associated with an oral temperature of >38.0 °C or requiring hospitalization at time of enrollment. Any of the following serological findings at Screening: positive Hepatitis B surface antigen (HBsAg), positive Hepatitis C (anti-HCV), or positive human immunodeficiency virus (HIV). Personal or family history of thymic pathology (e.g., thymoma), thymectomy, or myasthenia. History of significant allergic reaction to the vaccine components Asplenia, functional asplenia, or any condition resulting in the absence or removal of the spleen. Active or potentially progressive neurologic disease or injury including but not limited to: Parkinson's, Guillain Barré, epilepsy, seizures (except febrile seizures under the age of 2), cerebrovascular accident, head trauma requiring hospitalization within the preceding 3 years, or any other neurologic condition thought to impact the integrity of the blood brain barrier. Clinically significant abnormal ECG findings at Screening Impaired hepatic function, and/or clinically significant or unexplained elevations of alanine aminotransferase (ALT, SGPT), or aspartate aminotransferase (AST, SGOT) > 3X the upper limit of normal. Impaired renal function, as shown by but not limited to, serum creatinine >2.0 mg/dL. Impaired hematopoietic function and/or clinically significant hematological laboratory abnormalities. A history of alcohol or drug abuse within 12 months prior to study entry. Pregnant or lactating women and women of childbearing potential who are not using an acceptable method of contraception at least 28 days prior to enrollment. Post menopausal women will be considered not of childbearing potential 1 year after last menstrual period. Behavioral, cognitive, or psychiatric disease that, in the opinion of the Investigator affects the ability of the subject to understand the scope of the study and/or unlikely to be able to be compliant with the study procedures and visits. Any other condition, which in the Investigator's judgment, might result in an increased risk to the subject, or would affect the subject's participation in the study. Participation in another clinical trial investigating a vaccine, drug or medical procedure in the 30 days preceding informed consent. Any vaccine administered within 30 days prior to study vaccination. Note: Influenza vaccine can be administered 1 week preceding study vaccination. Planned participation in another clinical trial during the present trial period. Planned receipt of any vaccine in the 4 weeks following the trial vaccination. Research site personnel or their family members cannot be enrolled as subjects in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ChimeriVax WN02 vaccine, low dose<br>Participants randomized to receive ChimeriVax WN02 vaccine, low dose | Biological: ChimeriVax-WN02 vaccine<br>* low dose, approximately 4 x 3log10, given one time subcutaneously<br>|
| Experimental: ChimeriVax-WN02 vaccine, medium dose<br>Participants randomized to receive ChimeriVax-WN02 vaccine, medium dose | Biological: ChimeriVax-WN02 vaccine<br>* medium dose, approximately 4 x 4log10, given one time<br>|
| Experimental: ChimeriVax-WN02 vaccine, high dose<br>Participants randomized to receive ChimeriVax-WN02 vaccine, high dose | Biological: ChimeriVax-WN02 vaccine<br>* high dose, approximately 4 x 5log10, given one time subcutaneously<br>|
| Placebo Comparator: Placebo<br>Participants randomized to receive Placebo (Saline) | Biological: Placebo<br>* 0.9%Normal Saline for Injection, given one time subcutaneously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Antibodies to Vaccination With ChimeriVax™ WN02 or a Placebo Vaccine | Antibodies to the vaccine antigens were measured by the Plaque Reduction Neutralization Test. | Day 0 and Day 28 post-vaccination | 
| Number of Participants With Seroconversion Following Vaccination With ChimeriVax™ WN02 or a Placebo Vaccine. | Antibodies to vaccine were measured by the Plaque Reduction Neutralization Test. Seroconversion was defined as a four-fold or greater rise in titer between pre- and post-injection samples; or a post-vaccination (Day 28) titers of ≥ 1:20 in participants with baseline titer ≤ 1:10. | Day 0 and Day 28 post-vaccination | 
| Number of Participants Reporting Solicited Injection Site or Systemic Reactions Following Vaccination With ChimeriVax™ WN02 or a Placebo Vaccine. |  | Day 0 up to Day 14 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Developing Viremia After Vaccination With ChimeriVax™ WN02 or a Placebo Vaccine. | Viremia is defined as number of subjects in the analysis population dose group with detected (≥ 20 Plaque forming units [pfu]/mL) viremia at the reported visit. | Day 2 up to Day 14 post-vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
West Nile Fever, ChimeriVax, West Nile Virus Vaccine