Safety of and Immune Response to a Tick-Borne Encephalitis Vaccine (LGT(TP21)/DEN4) in Healthy Adults

January 18, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Phase 1 Study of the Safety and Immunogenicity of Tick-Borne Langat/Dengue 4 Chimera (LGT(TP21)/DEN4), a Live Attenuated Vaccine for Tick-Borne Encephalitis

Tick-borne encephalitis (TBE) is a viral illness common in the Northern Hemisphere, especially Europe and Asia. TBE infection may lead to central nervous system problems and death. The purpose of this study is to test the safety of and immune response to a TBE vaccine in healthy adults. The vaccine is related to a live attenuated virus developed against dengue virus infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

TBE is a common illness in Europe and Asia, where it is usually associated with mild illness but sometimes leads to long-term symptoms and even death. This study will evaluate the safety and immunogenicity of a live attenuated chimeric virus, LGT(TP21)/DEN4, which is derived from the Langat flavivirus and DEN4 dengue virus serotypes.

Each volunteer will be involved in the study for 180 days. Participants in Cohort 1 will be randomly assigned to receive LGT(TP21)/DEN4 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a higher dose of LGT(TP21)/DEN4 or placebo.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days and on Day 19. Study visits will occur every other day after vaccination until Day 16, followed by 5 additional visits at selected days through Day 180. Blood collection and a targeted physical exam will occur at each study visit. Some participants will be asked to undergo a skin biopsy or additional blood collection at selected visits.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2581
        • Vanderbilt University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and available to be followed for the duration of the study
  • Willing to use acceptable means of contraception
  • Good general health

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
  • Blood disease
  • History of migraine headaches
  • History of encephalitis
  • Alcohol or drug use that has caused medical, occupational, or family problems within 12 months prior to study entry
  • History of severe allergic reaction or anaphylaxis
  • Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
  • HIV-1 infected
  • Hepatitis C virus infected
  • Hepatitis B surface antigen positive
  • Known immunodeficiency syndrome
  • Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
  • Live vaccine within 4 weeks prior to study entry
  • Killed vaccine within 2 weeks prior to study entry
  • Blood products within 6 months prior to study entry
  • Investigational drug or vaccine within 3 months prior to study entry
  • Previously received a licensed or experimental yellow fever, tick-borne encephalitis, or dengue vaccine
  • Surgical removal of spleen
  • History of tick-borne encephalitis
  • History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus, Japanese encephalitis virus)
  • Other condition that, in the opinion of the investigator, would affect the participant's participation in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 1
One subcutaneous vaccination with a 10^3 PFU dose of LGT(TP21)/DEN4 vaccine given in the deltoid region of either arm. A second booster vaccination will be given 6 months after the first vaccination.
Biological: LGT(TP21)/DEN4
Live attenuated LGT(TP21)/DEN4 vaccine (one of two doses)
EXPERIMENTAL: 2
One subcutaneous vaccination with a 10^5 PFU dose of LGT(TP21)/DEN4 vaccine given in the deltoid region of either arm. A second booster vaccination will be given 6 months after the first vaccination. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.
Biological: LGT(TP21)/DEN4
Live attenuated LGT(TP21)/DEN4 vaccine (one of two doses)
PLACEBO_COMPARATOR: 3
One subcutaneous vaccination with a placebo vaccine given in the deltoid region of either arm. A second placebo vaccination will be given 6 months after the first vaccination.
Biological: Placebo
Placebo for LGT(TP21)/DEN4 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of vaccine-related adverse effects, graded by intensity and severity through active and passive surveillance
Time Frame: Throughout study
Throughout study
Immunogenicity of vaccine against anti-Langat neutralizing antibody
Time Frame: At Days 0, 28, 42, and 180
At Days 0, 28, 42, and 180

Secondary Outcome Measures

Outcome Measure
Time Frame
Recovery of virus from the blood of a vaccinee or seroconversion
Time Frame: Throughout study
Throughout study
Immunogenicity of the LGT(TP21)/DEN4 vaccine against other TBE viruses
Time Frame: Throughout study
Throughout study
Durability of antibody responses to Langat and other TBE viruses
Time Frame: At Day 180
At Day 180

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins Bloomberg School of Public Health

Investigators

  • Principal Investigator: Peter Wright, MD, Vanderbilt University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Primary Completion (ACTUAL)

July 1, 2007

Study Completion (ACTUAL)

July 1, 2007

Study Registration Dates

First Submitted

July 8, 2005

First Submitted That Met QC Criteria

July 8, 2005

First Posted (ESTIMATE)

July 12, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

January 21, 2008

Last Update Submitted That Met QC Criteria

January 18, 2008

Last Verified

January 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIR 182
  • H.22.03.09.26.B2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe