Humoral Response to Tick-borne Encephalitis Vaccine in Elderly

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lars Rombo, Sormland County Council, Sweden
ClinicalTrials.gov Identifier:
NCT01361776
First received: May 25, 2011
Last updated: November 17, 2015
Last verified: November 2015
  Purpose
Antibody titers after tick-borne encephalitis (TBE) vaccination are less in elderly and vaccination breakthroughs are more common in this age group. This has prompted Swedish authorities to recommend an additional dose in the initial vaccination schedule (= 0+30+90 days instead of the usually recommended 0+30 days. The investigators intend to evaluate this regime.

Condition Intervention Phase
Tick-borne Encephalitis
Biological: FSME-immune
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Humoral Response to TBE Vaccine in Elderly (50+ Year Olds) After Changed Dosage Intervals/Number of Doses?

Resource links provided by NLM:


Further study details as provided by Sormland County Council, Sweden:

Primary Outcome Measures:
  • Serum concentration of neutralising antibodies against TBE one month after two or three doses. [ Time Frame: 18 months after the first dose ] [ Designated as safety issue: No ]
    Determination of neutralising antibodies one month after completion of the first years vaccination series


Secondary Outcome Measures:
  • Serum concentration of neutralising antibodies against TBE one month after the dose which will be given a year later [ Time Frame: 18 months after the first dose has been given ] [ Designated as safety issue: No ]
    Determination of neutralising antibodies one month after the dose which will be given a year later


Enrollment: 200
Study Start Date: September 2011
Study Completion Date: June 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: TBE vaccine at 0+30 days
This group of 50 participants will follow the standard recommendation and will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 days during the first year and an additional dose one year later
Biological: FSME-immune
0.5 ml im as scheduled in the 4 arms
Active Comparator: TBE vaccine at 0+7+21 days
This group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 7 +21 days during the first year and an additional dose one year later
Biological: FSME-immune
0.5 ml im as scheduled in the 4 arms
Active Comparator: TBE vaccinte at 0+30+90 days
This group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 + 90 days during the first year and an additional dose one year later
Biological: FSME-immune
0.5 ml im as scheduled in the 4 arms
Active Comparator: younger participants
This group of 50 participants in the age group 18-49 years will be given TBE vaccine 0.5 ml FSME immune at 0 +30 days during the first year and an additional dose one year later
Biological: FSME-immune
0.5 ml im as scheduled in the 4 arms

Detailed Description:

The risk for TBE increases in Sweden. Together with an increased awareness of the possibility to acquire protection by vaccination, this has led to an increase in the number of doses of the vaccine distributed in Sweden each year -now being approximately 400.000. The first year, two doses with an interval of 1 month is recommended for the general population, followed by a third dose approximately one year later and an additional booster dose three years after the third.

Recent studies show that the antibody titers against TBE are substantially less in an older population. This is in line with the present recommendation from Austria that booster intervals should be shortened to 3 years in the age group 60+. It is also in line with a report of vaccination failures where 13/27 patients were older than 60 years According to a study by Jilkowa et al, 18 % (38/185) in the age group 60+ did not achieve putative levels of antibody titers after the first two doses. Therefore, the manufacturer of Encepur recommends a total of three doses to this age group using the same regimen as with "accelerated vaccination schedule (0+7+21 days). Unfortunately, GMT (geometrical mean of titers) after 3 doses with the accelerated schedule are not superior to 2 doses given at 0+30 days.

The manufacturer of FSME-immun instead recommends that serology should be checked one month after the second dose and that a third dose should be given if titers are not sufficient (0+30+60 days). Unfortunately, determinations of titers in a large number of samples put severe strain on logistics and is not feasible in Sweden.

In order to try to improve immunity in the age group 60+ , the Department of Communicable Disease Control and Prevention in Stockholm therefore recommends a third dose two months after the first two doses to the age group 60+ (0+30+60 days).

Study design. The investigators intend to give FSME-immune to 3 groups with varying vaccination schedules ( 0+7+21, 0+30 or 0+30+90. 50 participants will be randomized to each group. Half of them will be between 50-59 years and half will be at least 60 years old. A younger age group (50 participants between 18-49 years) will serve as controls and will be given FSME-immune according to standard recommendations (0+30 days).

Serum samples (10 ml of blood) will be obtained at five times: 0,60,120,360 and 400 days after first dose Samples will be analysed for neutralising antibodies at the Swedish institute for Infectious disease control - other options possible.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 50 years or more
  • generally healthy
  • no immunosuppressive condition
  • fertile women must use contraceptives

Exclusion Criteria:

  • Previous TBE infection
  • Previously immunized with TBE vaccine
  • Anaphylactic reaction to egg protein
  • Any disease or therapy which might suppress the immune response
  • Vaccination should be delayed if a participant has fever
  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: NCT01361776

Locations
Finland
Dept infectious diseases
Helsingfors, Finland, 00029
Sweden
Dept infectious diseases
Eskilstuna, Sweden, 631 88
Dept infectious diseases
Karlstad, Sweden, 651 85
Department of infectious diseases
Stockholm, Sweden, 17176
Dept infectious diseases
Uppsala, Sweden, 751 85
Department of infectious diseases
Örebro, Sweden
Sponsors and Collaborators
Sormland County Council, Sweden
Investigators
Principal Investigator: lars rombo, MD Karolinska Institutet
  More Information

Responsible Party: Lars Rombo, professor, Sormland County Council, Sweden
ClinicalTrials.gov Identifier: NCT01361776     History of Changes
Other Study ID Numbers: 2011/4-31/2 
Study First Received: May 25, 2011
Last Updated: November 17, 2015
Health Authority: Sweden: Medical Products Agency

Keywords provided by Sormland County Council, Sweden:
immune response
TBE-vaccine
elderly
additional doses

Additional relevant MeSH terms:
Encephalitis
Encephalitis, Tick-Borne
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Arbovirus
Arbovirus Infections
Virus Diseases
Tick-Borne Diseases
Encephalitis, Viral
Central Nervous System Viral Diseases
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Infectious Encephalitis
Central Nervous System Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016