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

Tick-Borne Encephalitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118924
• Other study ID #: CIR 182
• Secondary ID: H.22.03.09.26.B2
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2005
• Last updated: January 18, 2008
• Start date: July 2005
• Est. completion date: July 2007

Study information

• Verified date: January 2008
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Tick-Borne
• Tick-Borne Encephalitis

Intervention

Biological:
• LGT(TP21)/DEN4
Live attenuated LGT(TP21)/DEN4 vaccine (one of two doses)
• Placebo
Placebo for LGT(TP21)/DEN4 vaccine

Locations

Country	Name	City	State
United States	Vanderbilt University School of Medicine	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Johns Hopkins Bloomberg School of Public Health

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of vaccine-related adverse effects, graded by intensity and severity through active and passive surveillance		Throughout study	No
Primary	Immunogenicity of vaccine against anti-Langat neutralizing antibody		At Days 0, 28, 42, and 180	No
Secondary	Recovery of virus from the blood of a vaccinee or seroconversion		Throughout study	No
Secondary	Immunogenicity of the LGT(TP21)/DEN4 vaccine against other TBE viruses		Throughout study	No
Secondary	Durability of antibody responses to Langat and other TBE viruses		At Day 180	No