A Safety and Immunogenicity Trial With an Adjuvanted Tuberculosis (TB) Subunit Vaccine in Purified Protein Derivative (PPD) Positive Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety profile of an adjuvanted TB subunit vaccine administered at 0 and 2 months.

Official Title
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A Safety and Immunogenicity Phase 1 Trial With an Adjuvanted TB Subunit Vaccine (Ag85B-ESAT-6 + IC31)Administered in PPD Positive Volunteers at 0 and 2 Months

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: 50 microg. antigen + adjuvant (500 nmol KLK + 20 nmol ODN1a)
* Biological: 50 microg. antigen + adjuvant (500 nmol KLK + 20 nmol ODN1a)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female between 18 and 55 years old BCG group: Known to be BCG-vaccinated over 2 years before, PPD positive (range 6-15 mm or any documented value between 6-15 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: Known to be treated for latent TB, PPDpositive (equal or over 10 mm or documented equal or over 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: Granulomatous disease (by chest X-ray) Vaccinated with live vaccine 3 months before first vaccination Administration of immune modulating drugs (steroids, immunosuppressive drugs or immunoglobulins) 3 months before the first vaccination 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 judged by PI to be clinically relevant Pregnant women/planned pregnancy and/or breastfeeding within the trial period

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: Latent TB infection group<br>The latent TB group will receive two injections of 50 microgram antigen + adjuvant (500 nmol KLK + 20 nmol ODN1a)two months apart. | Biological: 50 microg. antigen + adjuvant (500 nmol KLK + 20 nmol ODN1a)<br>* o,5 mL suspension for injection x 2 with 2 months interval<br>* Other names: Antigen H1 + adjuvant IC31;|
| Experimental: BCG vaccinated group<br>The BCG vaccinated group will receive two vaccinations of 50 microgram antigen + adjuvant (500 nmol KLK + 20 nmol ODN1a)two months apart | Biological: 50 microg. antigen + adjuvant (500 nmol KLK + 20 nmol ODN1a)<br>* o,5 mL suspension for injection x 2 with 2 months interval<br>* Other names: Antigen H1 + adjuvant IC31;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical examination. Local adverse events.Systemic adverse events. Laboratory safety tests including urine safety tests. |  | From first vaccination until 8 months after the first vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection by ELISPOT of IFNgamma spot-forming cells in PBMCs. Detection by ELISA of IFNgamma production in supernatants of PBMC. Detection by ELISA of IgG antibodies in serum/plasma. Detection by Elisa of TNFalfa and IFNgamma in serum |  | From first vaccination until 8 months after first vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Vaccine, Ag85B, ESAT-6, IC31