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Safety and Immunogenicity of ChimeriVax-WN02 West Nile Vaccine in Healthy Adults

Primary Purpose

West Nile Fever

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
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
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for West Nile Fever focused on measuring West Nile Disease, Antibody response, Viremia, Safety, Tolerability, Prevention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • HOPE Research Institute
  • Idaho Infectious Diseases, PLLC
  • PRA International Clinical Pharmacology Center
  • Bio-Kinetic Clinical Applications, Inc.
  • The Glennan Centre for Geriatrics and Gerontologyy, EVMS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Group 1: WN02 Low Dose (Part 1)

Group 2: WN02 Medium Dose (Part 1)

Group 3: WN02 High Dose (Part 1)

Group 4: Placebo (Part 1)

Group 5: WNO2 High Dose (Part 2)

Group 6: Placebo (part 2)

Arm Description

Low Dose in healthy adults in Part 1 against a placebo control.

Medium dose level in part one healthy subjects against a placebo control.

High dose level in part one healthy subjects against a placebo control

Participants will receive a single dose of saline in Part 1 on Day 0

Participants enrolled in Part 2 and received a single dose of West Nile Virus vaccine.

Participants will receive a single dose of saline in Part 2 on Day 0

Outcomes

Primary Outcome Measures

Number of Participants With Fourfold or Greater Post-vaccination Titers (Seroconversion).
Seroconversion was defined as a fourfold or greater rise in titer between pre- and post-immunization samples
Number of Viremic Participants Post-vaccination
Viremic = detectable level of ≥ 10 plaque-forming units (PFU)/mL
Treatment-emergent Adverse Events Reported As Related to Study Treatment in at Least 5% of Participants in Any Active Treatment Group Post-vaccination.

Secondary Outcome Measures

Geometric Mean Titers of Neutralizing Antibody Titers Pre- and Post-vaccination.

Full Information

First Posted
February 27, 2007
Last Updated
April 12, 2016
Sponsor
Sanofi Pasteur, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00442169
Brief Title
Safety and Immunogenicity of ChimeriVax-WN02 West Nile Vaccine in Healthy Adults
Official Title
Randomized, Double-blind, Placebo Controlled Phase II Trial of the Safety, Tolerability and Immunogenicity of Lyophilized ChimeriVax-WN02 West Nile Vaccine in Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed Description
West Nile Disease has been carried across the United States by migrating birds since it was first identified in New York city in 1999. It is transmitted by mosquitoes from birds to humans and can cause severe disease in some individuals. There is no specific treatment for West Nile Disease. The target population for a West Nile vaccine is older people, as they are more susceptible to severe disease. This trial includes a dose-finding part with a placebo control in young healthy adults, followed by a placebo-controlled examination of the chosen dose in older healthy adults. Outcome measures include a comparison of adverse events between active treatment and placebo, a comparison of antibody and viremia measurements between dose levels and across age groups for the dose chosen for Part 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
West Nile Fever
Keywords
West Nile Disease, Antibody response, Viremia, Safety, Tolerability, Prevention

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
208 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: WN02 Low Dose (Part 1)
Arm Type
Experimental
Arm Description
Low Dose in healthy adults in Part 1 against a placebo control.
Arm Title
Group 2: WN02 Medium Dose (Part 1)
Arm Type
Experimental
Arm Description
Medium dose level in part one healthy subjects against a placebo control.
Arm Title
Group 3: WN02 High Dose (Part 1)
Arm Type
Experimental
Arm Description
High dose level in part one healthy subjects against a placebo control
Arm Title
Group 4: Placebo (Part 1)
Arm Type
Placebo Comparator
Arm Description
Participants will receive a single dose of saline in Part 1 on Day 0
Arm Title
Group 5: WNO2 High Dose (Part 2)
Arm Type
Experimental
Arm Description
Participants enrolled in Part 2 and received a single dose of West Nile Virus vaccine.
Arm Title
Group 6: Placebo (part 2)
Arm Type
Placebo Comparator
Arm Description
Participants will receive a single dose of saline in Part 2 on Day 0
Intervention Type
Biological
Intervention Name(s)
ChimeriVax-WN02 Low Dose
Intervention Description
Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region.
Intervention Type
Biological
Intervention Name(s)
ChimeriVax-WN02 Medium Dose
Intervention Description
Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region
Intervention Type
Biological
Intervention Name(s)
ChimeriVax-WN02 High Dose
Intervention Description
Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region
Intervention Type
Biological
Intervention Name(s)
0.9% Saline solution
Intervention Description
Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region
Intervention Type
Biological
Intervention Name(s)
ChimeriVax-WN02 High Dose
Intervention Description
Single dose formulation given in a volume of 0.5 mL by subcutaneous injection to the deltoid region
Intervention Type
Biological
Intervention Name(s)
0.9 % NaCl solution
Intervention Description
Single dose given in a volume of 0.5 mL by subcutaneous injection to the deltoid region
Primary Outcome Measure Information:
Title
Number of Participants With Fourfold or Greater Post-vaccination Titers (Seroconversion).
Description
Seroconversion was defined as a fourfold or greater rise in titer between pre- and post-immunization samples
Time Frame
Day 28 post-vaccination
Title
Number of Viremic Participants Post-vaccination
Description
Viremic = detectable level of ≥ 10 plaque-forming units (PFU)/mL
Time Frame
Day 21 post-vaccination
Title
Treatment-emergent Adverse Events Reported As Related to Study Treatment in at Least 5% of Participants in Any Active Treatment Group Post-vaccination.
Time Frame
Days 0 to 28 post-vaccination
Secondary Outcome Measure Information:
Title
Geometric Mean Titers of Neutralizing Antibody Titers Pre- and Post-vaccination.
Time Frame
Days 0, 14, and 28 post-vaccination
Other Pre-specified Outcome Measures:
Title
Number of Participants With Positive Immunoglobulin M (IgM) Response Post-vaccination in the As Treat Per-Protocol Population
Time Frame
Days 14 and 28 post-vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sanofi Pasteur Inc.
Official's Role
Study Director
Facility Information:
Facility Name
HOPE Research Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85050
Country
United States
Facility Name
Idaho Infectious Diseases, PLLC
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
PRA International Clinical Pharmacology Center
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66219
Country
United States
Facility Name
Bio-Kinetic Clinical Applications, Inc.
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65802
Country
United States
Facility Name
The Glennan Centre for Geriatrics and Gerontologyy, EVMS
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21148499
Citation
Biedenbender R, Bevilacqua J, Gregg AM, Watson M, Dayan G. Phase II, randomized, double-blind, placebo-controlled, multicenter study to investigate the immunogenicity and safety of a West Nile virus vaccine in healthy adults. J Infect Dis. 2011 Jan 1;203(1):75-84. doi: 10.1093/infdis/jiq003.
Results Reference
derived
Links:
URL
http://www.sanofipasteur.com
Description
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Safety and Immunogenicity of ChimeriVax-WN02 West Nile Vaccine in Healthy Adults

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