A Phase I Trial of a LTK63 Adjuvated Tuberculosis Nasal Subunit Vaccine (Ag85B-ESAT6) (TMUVA-01)

This study has been terminated.
(Safety Issues)
Sponsor:
Collaborators:
Statens Serum Institut
Novartis Vaccines
European Union
Information provided by:
St George's, University of London
ClinicalTrials.gov Identifier:
NCT00440544
First received: February 26, 2007
Last updated: October 31, 2008
Last verified: October 2008
  Purpose

The purpose of this study is to determine whether a subunit tuberculosis vaccine given as two nasal immunizations composed of a hybrid protein antigen from M. tuberculosis virus mixed with a toxoid adjuvant, causes untoward adverse reactions when administered to healthy adult volunteers. Both subjects who have not received Bacillus Calmette-Guerin (BCG) and subjects who have already received BCG will be enrolled. An initial evaluation of immune responses to the vaccine will also be undertaken.


Condition Intervention Phase
Tuberculosis
Biological: Ag85B-ESAT6 fusion protein H1
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase I Trial of the Safety and Immunogenicity of an Adjuvated TB Subunit Vaccine (Ag85B-ESAT6 + LTK63) Administered at 0 and 2 Months

Resource links provided by NLM:


Further study details as provided by St George's, University of London:

Primary Outcome Measures:
  • To evaluate the safety profile (medical examinations, adverse events and laboratory safety tests) of a nasal TB subunit vaccine with and without adjuvant given as two doses with 2 months interval. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the cell mediated and humoral immunogenicity profile of a nasal TB subunit vaccine with and without adjuvant, given as two doses with 2 months interval. [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: January 2007
Study Completion Date: February 2008
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
100 ug H1 antigen alone in BCG naive subjects
Biological: Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen in BCG naive subjects
Experimental: 2
100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects
Biological: Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects
Experimental: 3
50 ug H1 antigen in BCG immunized subjects
Biological: Ag85B-ESAT6 fusion protein H1
50 ug H1 antigen in BCG immunized subjects
Experimental: 4
50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects
Biological: Ag85B-ESAT6 fusion protein H1
50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects
Experimental: 5
100 ug H1 antigen in BCG immunized subjects
Biological: Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen in BCG immunized subjects
Experimental: 6
100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects
Biological: Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Detailed Description:

The purpose of this study is to determine whether a subunit tuberculosis vaccine given as two nasal immunizations composed of a hybrid protein antigen from M. tuberculosis virus mixed with a toxoid adjuvant, causes untoward adverse reactions when administered to healthy adult volunteers. Both subjects who have not received BCG and subjects who have already received BCG will be enrolled. An initial evaluation of immune responses to the vaccine will also be undertaken using flow cytometry to enumerate antigen specific IFNg containing T cells; ELISPOT to determine IFNg secreting antigen specific T cells; serology and nasal wash antibody.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Healthy, based on medical examination at inclusion
  • Male or female subjects, aged between 18 and 55 years
  • Willing and likely to be able to comply with the trial procedures
  • Prepared to grant authorized persons access to their medical records

Additional inclusion criterion for BCG-non-vaccinated subjects:

  • BCG-non-vaccinated (i.e., absence of a BCG-scar)
  • Negative Mantoux skin test

Additional inclusion criterion for BCG-vaccinated subjects:

  • BCG-vaccinated (i.e., presence of a BCG-scar)

Exclusion Criteria:

  • History of TB or known exposure to TB
  • Radiological findings on chest X ray compatible with previous or current infection with tuberculosis
  • Positive QuantiFERON® TB-Gold test Evidence of previous, current or latent tuberculosis
  • Evidence of previous, current or latent tuberculosis
  • History of severe organ-system diseases
  • Known hypersensitivity to any of the vaccine components
  • History of allergic disorders
  • Vaccinated with other vaccine within 3 months before first vaccination
  • Congenital and/or acquired immune diseases
  • Administration of systemic immune modulating drugs (steroids, immunosuppressive drugs or immunoglobulin) within 3 months before the first vaccination (topical steroids not included)
  • Autoimmune diseases
  • HIV, HBV and HCV sero-positive
  • Established diagnosis of a neurological or neuromuscular disease, and specifically any history of abnormality with respect to sense of smell (olfactory nerve dysfunction), or previous or current facial nerve paralysis
  • Congenital or acquired abnormalities or disorders related to nasal and nasopharyngeal cavities
  • Current use of any medication taken through the nasal/inhalatory route including cocaine or other drugs
  • Laboratory parameters outside of normal ranges considered clinically significant
  • Pregnant according to urine pregnancy test
  • Females not willing to use contraceptives or who are breastfeeding
  • Intake of trial medication in other clinical trials within 6 months of the first vaccination
  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: NCT00440544

Locations
United Kingdom
St George's Vaccine Institute
London, England, United Kingdom, SW17 0RE
Sponsors and Collaborators
St George's, University of London
Statens Serum Institut
Novartis Vaccines
European Union
Investigators
Principal Investigator: David JM Lewis, MD St George's, University of London, UK
  More Information

Additional Information:
No publications provided

Responsible Party: David JM Lewis, Principal Investigator, SGUL
ClinicalTrials.gov Identifier: NCT00440544     History of Changes
Other Study ID Numbers: TMUVA-01, EudraCT Number: 2005-005140-81, FP6-2002-LIFESCIHEA-2.3 503240
Study First Received: February 26, 2007
Last Updated: October 31, 2008
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by St George's, University of London:
Tuberculosis
vaccine
nasal immunization

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 01, 2014