A Phase I Trial of a LTK63 Adjuvated Tuberculosis Nasal Subunit Vaccine (Ag85B-ESAT6) - Full Text View

Sponsors and Collaborators:	St George's, University of London Statens Serum Institut Novartis Vaccines Commission of the European Union
Information provided by:	St George's, University of London
ClinicalTrials.gov Identifier:	NCT00440544

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 I

MedlinePlus related topics: Tuberculosis

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Active Control, Parallel Assignment, Safety Study
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

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
1: Experimental 100 ug H1 antigen alone in BCG naive subjects	Biological: Ag85B-ESAT6 fusion protein H1 100 ug H1 antigen in BCG naive subjects
2: Experimental 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
3: Experimental 50 ug H1 antigen in BCG immunized subjects	Biological: Ag85B-ESAT6 fusion protein H1 50 ug H1 antigen in BCG immunized subjects
4: Experimental 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
5: Experimental 100 ug H1 antigen in BCG immunized subjects	Biological: Ag85B-ESAT6 fusion protein H1 100 ug H1 antigen in BCG immunized subjects
6: Experimental 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00440544

Locations

United Kingdom, England
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

Commission of the European Union

Investigators

Principal Investigator:

David JM Lewis, MD

St George's, University of London, UK

More Information

St George's Vaccine Institute Home website This link exits the ClinicalTrials.gov site

MUVAPRED website of the European Union consortium funding the project This link exits the ClinicalTrials.gov site

Responsible Party:	SGUL ( David JM Lewis, Principal Investigator )
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
ClinicalTrials.gov Identifier:	NCT00440544
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

Study placed in the following topic categories:

Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Tuberculosis

Additional relevant MeSH terms:

Actinomycetales Infections

ClinicalTrials.gov processed this record on January 14, 2009