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

Tuberculosis Clinical Trial

— TMUVA-01  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00440544
• Other study ID #: TMUVA-01
• Secondary ID: EudraCT Number:
• Status: Terminated
• Phase: Phase 1
• First received: February 26, 2007
• Last updated: October 31, 2008
• Start date: January 2007
• Est. completion date: February 2008

Study information

• Verified date: October 2008
• Source: St George's, University of London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: February 2008
• Est. primary completion date: November 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Biological:
• Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen in BCG naive subjects
• Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects
• Ag85B-ESAT6 fusion protein H1
50 ug H1 antigen in BCG immunized subjects
• Ag85B-ESAT6 fusion protein H1
50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects
• Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen in BCG immunized subjects
• Ag85B-ESAT6 fusion protein H1
100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Locations

Country	Name	City	State
United Kingdom	St George's Vaccine Institute	London	England

Sponsors (4)

Lead Sponsor	Collaborator
St George's, University of London	European Union, Novartis Vaccines, Statens Serum Institut

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		8 months	Yes
Secondary	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.		8 months	No

External Links

•   MUVAPRED website of the European Union consortium funding the project
•   St George's Vaccine Institute Home website