Clinical trial NCT00442169: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: West Nile Fever
Keywords: West Nile Disease
Antibody response
Viremia
Safety
Tolerability
Prevention
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-03-01
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Number of Participants With Fourfold or Greater Post-vaccination Titers (Seroconversion).
timeFrame: Day 28 post-vaccination
measure: Number of Viremic Participants Post-vaccination
timeFrame: Day 21 post-vaccination
measure: Treatment-emergent Adverse Events Reported As Related to Study Treatment in at Least 5% of Participants in Any Active Treatment Group Post-vaccination.
timeFrame: Days 0 to 28 post-vaccination
Secondary outcomes:
measure: Geometric Mean Titers of Neutralizing Antibody Titers Pre- and Post-vaccination.
timeFrame: Days 0, 14, and 28 post-vaccination
Other outcomes:
measure: Number of Participants With Positive Immunoglobulin M (IgM) Response Post-vaccination in the As Treat Per-Protocol Population
timeFrame: Days 14 and 28 post-vaccination
Locations:
city: Phoenix
country: United States
facility: HOPE Research Institute
state: Arizona
city: Idaho Falls
country: United States
facility: Idaho Infectious Diseases, PLLC
state: Idaho
city: Lenexa
country: United States
facility: PRA International Clinical Pharmacology Center
state: Kansas
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications, Inc.
state: Missouri
city: Norfolk
country: United States
facility: The Glennan Centre for Geriatrics and Gerontologyy, EVMS
state: Virginia
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
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.