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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I Trial of the Safety and Immunogenicity of an Adjuvated TB Subunit Vaccine (Ag85B-ESAT6 + LTK63) Administered at 0 and 2 Months

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: Ag85B-ESAT6 fusion protein H1
* Biological: Ag85B-ESAT6 fusion protein H1
* Biological: Ag85B-ESAT6 fusion protein H1
* Biological: Ag85B-ESAT6 fusion protein H1
* Biological: Ag85B-ESAT6 fusion protein H1
* Biological: Ag85B-ESAT6 fusion protein H1


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>100 ug H1 antigen alone in BCG naive subjects | Biological: Ag85B-ESAT6 fusion protein H1<br>* 100 ug H1 antigen in BCG naive subjects<br>|
| Experimental: 2<br>100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects | Biological: Ag85B-ESAT6 fusion protein H1<br>* 100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG naive subjects<br>|
| Experimental: 3<br>50 ug H1 antigen in BCG immunized subjects | Biological: Ag85B-ESAT6 fusion protein H1<br>* 50 ug H1 antigen in BCG immunized subjects<br>|
| Experimental: 4<br>50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects | Biological: Ag85B-ESAT6 fusion protein H1<br>* 50 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects<br>|
| Experimental: 5<br>100 ug H1 antigen in BCG immunized subjects | Biological: Ag85B-ESAT6 fusion protein H1<br>* 100 ug H1 antigen in BCG immunized subjects<br>|
| Experimental: 6<br>100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects | Biological: Ag85B-ESAT6 fusion protein H1<br>* 100 ug H1 antigen + LTK63 adjuvant 30 ug in BCG immunized subjects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, vaccine, nasal immunization