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

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins Bloomberg School of Public Health
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00118924
First received: July 8, 2005
Last updated: January 18, 2008
Last verified: January 2008
  Purpose

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.


Condition Intervention Phase
Tick-Borne Encephalitis
Biological: LGT(TP21)/DEN4
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of vaccine-related adverse effects, graded by intensity and severity through active and passive surveillance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Immunogenicity of vaccine against anti-Langat neutralizing antibody [ Time Frame: At Days 0, 28, 42, and 180 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recovery of virus from the blood of a vaccinee or seroconversion [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Immunogenicity of the LGT(TP21)/DEN4 vaccine against other TBE viruses [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Durability of antibody responses to Langat and other TBE viruses [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: July 2005
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118924

Locations
United States, Tennessee
Vanderbilt University School of Medicine
Nashville, Tennessee, United States, 37232-2581
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
Investigators
Principal Investigator: Anna Durbin, MD Center for Immunization Research, Johns Hopkins School of Public Health
Principal Investigator: Peter Wright, MD Vanderbilt University School of Medicine
  More Information

Publications:
Responsible Party: Anna Durbin, MD, Center for Immunization Research, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier: NCT00118924     History of Changes
Other Study ID Numbers: CIR 182, H.22.03.09.26.B2
Study First Received: July 8, 2005
Last Updated: January 18, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Dengue Vaccine
Tick-Borne Illnesses
Flavivirus

Additional relevant MeSH terms:
Encephalitis
Encephalitis, Tick-Borne
Central Nervous System Viral Diseases
Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Encephalitis, Arbovirus
Arbovirus Infections
Tick-Borne Diseases
Encephalitis, Viral
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on July 28, 2014