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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Center for Immunization Research
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00118924

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 I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety Study
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:

MedlinePlus related topics: Dengue Encephalitis

U.S. FDA Resources

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
1: Experimental 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)
2: Experimental 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)
3: Placebo Comparator 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

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

National Institute of Allergy and Infectious Diseases (NIAID)

Center for Immunization Research

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:

Beran J. Immunisation against tick-borne encephalitis by widely used vaccines: short-term history and current recommendations. Clin Microbiol Infect. 2005 May;11(5):424-6. No abstract available.

Chang GJ, Kuno G, Purdy DE, Davis BS. Recent advancement in flavivirus vaccine development. Expert Rev Vaccines. 2004 Apr;3(2):199-220.

Lai CJ, Monath TP. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis. Adv Virus Res. 2003;61:469-509. Review.

Pletnev AG, Bray M, Hanley KA, Speicher J, Elkins R. Tick-borne Langat/mosquito-borne dengue flavivirus chimera, a candidate live attenuated vaccine for protection against disease caused by members of the tick-borne encephalitis virus complex: evaluation in rhesus monkeys and in mosquitoes. J Virol. 2001 Sep;75(17):8259-67.

Responsible Party:	Center for Immunization Research, Johns Hopkins School of Public Health ( Anna Durbin, MD )
Study ID Numbers:	CIR 182, H.22.03.09.26.B2
Study First Received:	July 8, 2005
Last Updated:	January 18, 2008
ClinicalTrials.gov Identifier:	NCT00118924 History of Changes
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

Study placed in the following topic categories:

Dengue Fever
Central Nervous System Diseases
Healthy
Brain Diseases
Encephalitis
Tick-Borne Diseases
Encephalitis, Tick-Borne

Dengue Hemorrhagic Fever
Virus Diseases
Central Nervous System Infections
Dengue
Tick-borne Encephalitis
Arbovirus Infections

Additional relevant MeSH terms:

RNA Virus Infections
Flaviviridae Infections
Flavivirus Infections
Nervous System Diseases
Central Nervous System Diseases
Central Nervous System Viral Diseases
Brain Diseases
Encephalitis

Tick-Borne Diseases
Encephalitis, Tick-Borne
Virus Diseases
Encephalitis, Viral
Central Nervous System Infections
Arbovirus Infections
Encephalitis, Arbovirus

ClinicalTrials.gov processed this record on September 09, 2009