Clinical trial NCT00118924: Safety of and Immune Response to a Tick-Borne Encephalitis Vaccine (LGT(TP21)/DEN4) in Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tick-Borne Encephalitis
Keywords: Dengue Vaccine
Tick-Borne Illnesses
Flavivirus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Johns Hopkins Bloomberg School of Public Health
First posted: 2005-07-12
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Frequency of vaccine-related adverse effects, graded by intensity and severity through active and passive surveillance
timeFrame: Throughout study
measure: Immunogenicity of vaccine against anti-Langat neutralizing antibody
timeFrame: At Days 0, 28, 42, and 180
Secondary outcomes:
measure: Recovery of virus from the blood of a vaccinee or seroconversion
timeFrame: Throughout study
measure: Immunogenicity of the LGT(TP21)/DEN4 vaccine against other TBE viruses
timeFrame: Throughout study
measure: Durability of antibody responses to Langat and other TBE viruses
timeFrame: At Day 180
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
Study officials:
affiliation: Center for Immunization Research, Johns Hopkins School of Public Health
name: Anna Durbin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University School of Medicine
name: Peter Wright, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1111/j.1469-0691.2005.01115.x. No abstract available.
citation: Chang GJ, Kuno G, Purdy DE, Davis BS. Recent advancement in flavivirus vaccine development. Expert Rev Vaccines. 2004 Apr;3(2):199-220. doi: 10.1586/14760584.3.2.199.
citation: Lai CJ, Monath TP. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis. Adv Virus Res. 2003;61:469-509. doi: 10.1016/s0065-3527(03)61013-4.
citation: 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. doi: 10.1128/jvi.75.17.8259-8267.2001.