Vaccine Study for Tick-Borne Encephalitis Virus (TBEV)

NCT01031537 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 09024609-I-0246
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 2

Brief Summary

This was an open label trial of a non-US licensed vaccine for tick-borne encephalitis. The vaccine was licensed by Baxter, and now following an acquisition by Pfizer Inc in Vienna, Austria since 2001, and has an extensive safety record in multiple European countries. Field effectiveness studies suggest \> 99 percent protection against disease transmitted by the natural routes of either tick bite or ingestion of contaminated, unpasteurized milk. The vaccine is also considered to be effective against laboratory exposures and is used routinely for this purpose in European laboratories. The US Centers for Disease Control and Prevention and the National Institutes of Health acknowledge the effectiveness of the vaccine by allowing those who have received it to study tick-borne encephalitis virus (TBEV) in isolation facilities rated at BSL-3 rather than the more stringent BSL-4, with the exception of the Russian Spring-Summer Encephalitis strain. Subjects were recruited from personnel at 2 intramural campuses of the National Institute of Allergy and Infectious Diseases who may be exposed accidentally to any strain or serotype of viable TBEV. Approximately 160 individuals were eligible to participate. The rapid immunization schedule (injections on Days 0, 14, and 161) was used and subjects had labs drawn 21 days after the 2nd, 3rd and 4th vaccine injections to determine seroconversion. Subjects that seroconverted to TBEV were offered a booster dose of the vaccine 3 years from the date of receipt of the third dose of the vaccine. Subjects that were seropositive at entry into the study were offered a booster dose of the vaccine every 3 years from Day 0.

Conditions

Tick-Borne Encephalitis; Encephalitis, Tick-Borne; Tick-Borne Disease; Glycoprotein E, Flavivirus; NSI Protein, Flavivirus

Keywords

FSME-Immun; TBEV; TBE Researcher; Plavivirus; Anti-TBEV Levels; Tic-Borne Encephalitis

Outcome Measures

Primary Outcomes (2)

• TBEV Viral Neutralization Titer >1:10

  Tick borne encephalitis antibody viral neutralization titer levels (\>1:10)

  Baseline

• TBEV Viral Neutralization Titer >1:10

  The number of participants that develop anti-tick borne encephalitis antibody viral neutralization titer levels (\>1:10) following receipt of 3 doses of intramuscular FSME-IMMUN (vaccine series)

  6 months

Study Arms (1)

FSME-IMMUN 0.5mL Baxter

OTHER

FSME-IMMUN 0.5mL Baxter is non-US licensed vaccine for tick-borne encephalitis virus. The FSME-IMMUN 0.5mL Baxter is available as 0.5mL in a pre-loaded vaccine syringe. All participants received active vaccine using a rapid immunization schedule, with vaccine administration on Days 0, 14, 161 and 245. Participants that tested seropositive for tick-borne encephalitis virus or subjects that developed positive viral neutralizer titers after the 3rd or 4th vaccine were given a booster of FSME-IMMUN 0.5mL Baxter vaccine at 3, 6 and 9 years after enrollment.

Biological: FSME-IMMUN 0.5ml Baxter

Interventions

FSME-IMMUN 0.5ml Baxter BIOLOGICAL

Vaccine

FSME-IMMUN 0.5mL Baxter

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must meet the following criteria at study entry:
• Be engaged in activities that place them at potential risk of occupational exposure to TBEV in its viable form at one of the participating intramural laboratories of NIAID
• Be 18 years of age or older at the time of the first immunization.
• Comprehend the study requirements.
• Provide written informed consent to participate in this study.
• Be in good health as determined by the Investigator, based upon medical history and a targeted physical examination.
• Have a stable health status as determined by the Investigator.
• Have access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device (i.e., a common use phone serving multiple rooms or apartments).
• Express availability for the required study period, and ability to attend scheduled visits.

You may not qualify if:

• The following criteria should be checked at the time of the study entry. If any apply, the subject will not be included in the study:
• The subject must not be participating in any other trial of an investigational drug or vaccine for 1 month prior to the first injection through until 21 days after the third injection. (Given the nature of the work these study subjects engage in, exemptions to this proscription may be granted on a case by case basis after discussion between the Investigator and the IRB.)
• The presence on the day of immunization of an oral temperature of \>101.2 degrees F or acute symptoms other than mild severity.
• Active systemic infectious process as determined by review of systems and physical examination. The subject may be enrolled at a later date once the illness has resolved.
• Known immune suppression, such as that associated with human immunodeficiency virus infection, or other condition, to the extent that, in the opinion of the Investigator, the subject is likely to have a poor response to the vaccine. This information will be obtained by history only. Serologic screening for these diseases will not be performed.
• Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the Investigator to render the potential subject unable/unlikely to report promptly any adverse reactions to the vaccine.
• Current diagnosis of leukemia, Hodgkin s disease, non-Hodgkin s lymphoma, or any other cancer, autoimmune disease such as lupus, which is in and of itself a cause of immunosuppression to the point that, in the opinion of the Investigator, the subject is likely to have a poor response to the vaccine.
• Currently receiving systemic immunosuppressive chemotherapy or immunotherapy (including glucocorticoids) resulting in immune suppression to the point that, in the opinion of the Investigator, the subject is likely to have a poor response to the vaccine.
• Any neurological condition in which (in the opinion of the Investigator) the integrity of the blood brain barrier may have been compromised.
• Previous anaphylactic reaction to any TBE vaccine.
• Known or suspected anaphylactic reaction to any constituent of FSME IMMUN, to include formaldehyde, protamine sulfate, gentamicin and neomycin, or current egg allergy.
• Known pregnancy, or anticipating becoming pregnant in the first 8 months of the study or a positive urine beta-human chorionic gonadotropin (beta hCG) test result prior to immunization. If subjects become pregnant at some point in time after the 1st injection, no further injections will be given until after the pregnancy is completed, they are no longer nursing or have a negative beta-hCG result.
• Lactating or nursing.
• Women of child bearing potential (defined as pre-menopausal who have not undergone either hysterectomy or tubal ligation) who lack a history of reliable contraceptive practices. Reliable contraceptive practices (for the first 8 months of the study and within 21 days prior to or 42 days after booster immunizations) include:
• Consistent abstinence from heterosexual activity

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Rocky Mountain Laboratory (RML)

Hamilton, Montana, 59840, United States

Location

Related Publications (3)

• Adner N, Leibl H, Enzersberger O, Kirgios M, Wahlberg T. Pharmacokinetics of human tick-borne encephalitis virus antibody levels after injection with human tick-borne encephalitis immunoglobulin, solvent/detergent treated, FSME-BULIN S/D in healthy volunteers. Scand J Infect Dis. 2001;33(11):843-7. doi: 10.1080/00365540110027358.

  PMID: 11760166 BACKGROUND

• Baumhackl U, Franta C, Retzl J, Salomonowitz E, Eder G. A controlled trial of tick-borne encephalitis vaccination in patients with multiple sclerosis. Vaccine. 2003 Apr 1;21 Suppl 1:S56-61. doi: 10.1016/s0264-410x(02)00815-0.

  PMID: 12628815 BACKGROUND

• Charrel RN, Attoui H, Butenko AM, Clegg JC, Deubel V, Frolova TV, Gould EA, Gritsun TS, Heinz FX, Labuda M, Lashkevich VA, Loktev V, Lundkvist A, Lvov DV, Mandl CW, Niedrig M, Papa A, Petrov VS, Plyusnin A, Randolph S, Suss J, Zlobin VI, de Lamballerie X. Tick-borne virus diseases of human interest in Europe. Clin Microbiol Infect. 2004 Dec;10(12):1040-55. doi: 10.1111/j.1469-0691.2004.01022.x.

  PMID: 15606630 BACKGROUND

MeSH Terms

Conditions

Encephalitis, Tick-Borne; Tick-Borne Diseases

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Results Point of Contact

• Title: Dr. James M. Schmitt
• Organization: Division of Occupational Health and Safety, NIH

james_schmitt@nih.gov

301-496-4411

Study Officials

• James M Schmitt, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2009
• First Posted: December 14, 2009
• Study Start: September 25, 2009
• Primary Completion: December 23, 2016
• Study Completion: December 23, 2016
• Last Updated: July 5, 2018
• Results First Posted: July 5, 2018

Record last verified: 2018-04

Locations

US (2)