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

Primary Purpose

Tuberculosis

Status

Terminated

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Ag85B-ESAT6 fusion protein H1

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, vaccine, nasal immunization

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

St George's Vaccine Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Arm Description

100 ug H1 antigen alone in BCG naive subjects

100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects

50 ug H1 antigen in BCG immunized subjects

50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

100 ug H1 antigen in BCG immunized subjects

100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Outcomes

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.

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.

Full Information

NCT ID

NCT00440544

First Posted

February 26, 2007

Last Updated

October 31, 2008

Sponsor

St George's, University of London

Collaborators

Statens Serum Institut, Novartis Vaccines, European Union

1. Study Identification

Unique Protocol Identification Number

NCT00440544

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2008

Overall Recruitment Status

Terminated

Why Stopped

Safety Issues

Study Start Date

January 2007 (undefined)

Primary Completion Date

November 2007 (Actual)

Study Completion Date

February 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

St George's, University of London

Collaborators

Statens Serum Institut, Novartis Vaccines, European Union

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis, vaccine, nasal immunization

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

100 ug H1 antigen alone in BCG naive subjects

Arm Title

Arm Type

Experimental

Arm Description

100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects

Arm Title

Arm Type

Experimental

Arm Description

50 ug H1 antigen in BCG immunized subjects

Arm Title

Arm Type

Experimental

Arm Description

50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Arm Title

Arm Type

Experimental

Arm Description

100 ug H1 antigen in BCG immunized subjects

Arm Title

Arm Type

Experimental

Arm Description

100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Intervention Type

Biological

Intervention Name(s)

Ag85B-ESAT6 fusion protein H1

Intervention Description

100 ug H1 antigen in BCG naive subjects

Intervention Type

Biological

Intervention Name(s)

Ag85B-ESAT6 fusion protein H1

Intervention Description

100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects

Intervention Type

Biological

Intervention Name(s)

Ag85B-ESAT6 fusion protein H1

Intervention Description

50 ug H1 antigen in BCG immunized subjects

Intervention Type

Biological

Intervention Name(s)

Ag85B-ESAT6 fusion protein H1

Intervention Description

50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Intervention Type

Biological

Intervention Name(s)

Ag85B-ESAT6 fusion protein H1

Intervention Description

100 ug H1 antigen in BCG immunized subjects

Intervention Type

Biological

Intervention Name(s)

Ag85B-ESAT6 fusion protein H1

Intervention Description

100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David JM Lewis, MD

Organizational Affiliation

St George's, University of London, UK

Official's Role

Principal Investigator

Facility Information:

Facility Name

St George's Vaccine Institute

City

London

State/Province

England

ZIP/Postal Code

SW17 0RE

Country

United Kingdom

12. IPD Sharing Statement

Links:

URL

http://www.vaccine.ac.uk

Description

St George's Vaccine Institute Home website

Learn more about this trial

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

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