A Safety and Immunogenicity Trial With an Adjuvanted TB Subunit Vaccine (Ag85B-ESAT-6 + IC31)

Study Overview
=================
Brief Summary
-----------------
The study has the following objectives: Primary objective To evaluate the safety profile of an adjuvanted TB subunit vaccine administered in different antigen/adjuvant formulations at 0 and 2 months Secondary objective To determine the immunogenicity profile of an adjuvanted TB subunit vaccine administered in different antigen/adjuvant formulations at 0 and 2 months.

Detailed Description
-----------------
Number of trial subjects=48 Investigational product=Ag85B - ESAT-6 + IC31 Dosage Group 1: TST negative, 50 µg antigen Group 2: TST negative, 50 µg antigen + fixed adjuvant Group 3: BCG vaccinated, 50 µg antigen + fixed adjuvant Group 4 : Latent TB, 50 µg antigen + fixed adjuvant Dosage volume 0.5 ml Administration Intramuscularly into deltoid muscle, alternate arms at day 0 (right) and day 56 (left).

Official Title
-----------------
A Safety and Immunogenicity Phase 1 Trial With an Adjuvanted TB Subunit Vaccine (Ag85B-ESAT-6 + IC31) Administered in Different Antigen/Adjuvant Formulations in TST Negative and TST Positive Volunteers at 0 and 2 Months

Conditions
-----------------
Tuberculosis

Intervention / Treatment
-----------------
* Biological: Antigen (Ag85B-ESAT-6)
* Biological: Antigen (Ag85B-ESAT-6) with adjuvant (IC31)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male between 18 and 40 years old TST negative groups: TST- and negative QuantiFERON-TB Gold In tube test BCG group: known to be BCG-vaccinated > 2 years before(scar, vaccination card), TST+ (> 6 or any documented value > 6 mm on medical file in the past), with no active, chronic or past TB disease as confirmed by chest X ray, negative QuantiFERON-TB Gold In Tube test and negative 6-day lymphocyte tests. Infection group: latent TB, TST+ ( = or > 10 mm or documented = or > 10 mm positive on medical file in the past), previously TB infected but with no active disease confirmed by chest X ray, may have received chemoprophylaxis but with no TB treatment/chemoprophylaxis within the preceding 2 years, positive QuantiFERON-TB Gold In Tube test and/or positive 6-day lymphocyte test. Healthy based on medical examination/history at the inclusion Signed informed consent Prepared to grant authorized persons access to the medical records The volunteer is likely to comply with instructions Exclusion Criteria: Confirmed active TB based on clinical evaluation(history, physical findings and investigations) Vaccinated with any vaccine 3 months before first vaccination Administration of immune modulating drugs (steroids, immunosuppressive drugs or immunoglobulins) HBV, HCV or HIV sero-positive Participation in other clinical trials Known hypersensitivity to any of the vaccine components Laboratory parameters outside of normal range considered clinically relevant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12 TST negative volunteers antigen only<br> | Biological: Antigen (Ag85B-ESAT-6)<br>* Solution for injection, 0.5 mL, 50 ug antigen, 2 vaccinations with 2 months interval<br>|
| Experimental: 12 TST negative volunteers<br> | Biological: Antigen (Ag85B-ESAT-6) with adjuvant (IC31)<br>* Suspension for injection, 0.5 mL, 50 ug antigen, 2 vaccinations with 2 months interval<br>|
| Experimental: 12 BCG vaccinated volunteers<br> | Biological: Antigen (Ag85B-ESAT-6) with adjuvant (IC31)<br>* Suspension for injection, 0.5 mL, 50 ug antigen, 2 vaccinations with 2 months interval<br>|
| Experimental: 12 with Latent TB infection >= 2 years ago<br> | Biological: Antigen (Ag85B-ESAT-6) with adjuvant (IC31)<br>* Suspension for injection, 0.5 mL, 50 ug antigen, 2 vaccinations with 2 months interval<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety on Physical examination , and Laboratory safety tests of hematology clinical chemistry |  | 12 visits in a total of 224 days duratiion from the day of first vaccinantion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity assessment by: A.Detection of IFN gama production after stimulation with Ag85B, ESAT-6 and H1. B.Detection of IgG antibodies to recombinant proteins Ag85B, ESAT-6 and H1 in serum/plasma. |  | 12 visits in a total of 224 days duratiion from the day of first vaccinantion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
safety, immunogenicity, adjuvanted TB subunit vaccine