Evaluation of the Safety and Immunogenicity of the Recombinant Subunit Vaccine GamTBvac Against the Tuberculosis.

Study Overview
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Brief Summary
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The study is aimed to evaluate the safety and immunogenicity of the medicinal product GamTBvac - a recombinant subunit vaccine against the tuberculosis. The study is designed as a comparative placebo-controlled study with a two-fold increase of an applied dose among healthy volunteers aged 18-49 years.

Detailed Description
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The clinical trial study of the GamTBvac vaccine against the tuberculosis is a comparative placebo-controlled study with a two-fold increase of an applied dose among healthy volunteers aged 18-49 years. The product GamTBvac is a lyophilized substance consisted of the purified recombinant subunit antigens of Mycobacterium tuberculosis, that is applied for the preparing of the solution for a subcutaneous administration. Currently the study is at the first phase. The aims of the study are: a) to confirm the safety of the product in the healthy volunteers; b) to select the optimal administration dose; c) to evaluate of the immunogenicity of the vaccine; d) to investigate the immune cell memory as a response to the vaccination. The total number of the volunteers in the study is 60: at the first stage to estimate the safety and portable of the vaccine, two groups of volunteers each includes 12 persons got the single decreased dose (0.25 of the planned dose for regular administration) of the vaccine (the first group, 12 persons), and the 0.5 ml of the placebo (the second group, 12 persons); at the second stage to select the optimal dose and the scheme of the vaccine administration, additionally three groups, each consist of 12 persons of volunteers will be recruited. The first group will get double vaccination of a decreased dose (0.25 of the regular dose), the second group will get the double vaccination of a mean dose (0.5 of the regular dose), and the third one will get the double vaccination of the maximum (1.0 regular) dose. The inclusion criteria for the volunteers of the study are: healthy males either females aged 18-49 years who have previously got the BCG vaccine. The exclusion criterion is the presence of the latent tuberculosis in the patient that is confirmed during the preliminary laboratory screening.

Official Title
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Evaluation of the Safety and Immunogenicity of the Recombinant Subunit Vaccine GamTBvac Against the Tuberculosis. Comparative Placebo-controlled Study With a Two-fold Increase of the Vaccine Dose in Healthy Volunteers Aged 18-49 Years.

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: Single GamTBvac vaccination (0.25 dose)
* Biological: Placebo administration
* Biological: Double GamTBvac vaccination (0.25 dose)
* Biological: Double GamTBvac vaccination (0.5 dose)
* Biological: Double GamTBvac vaccination (1.0 dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: lack of the latent tuberculosis, laboratory confirmed BCG vaccination in the past signed informed consent Exclusion Criteria: presence of the latent tuberculosis, laboratory confirmed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: The clinical trial study of the GamTBvac vaccine against the tuberculosis is a comparative placebo-controlled study with a two-fold increase of an applied dose among healthy volonteers aged 18-49 years.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety and portable study group<br>12 persons who have got a single decreased dose (0.25 of the planned dose for regular administration) of the GamTBvac recombinant subunit vaccine. The intervention for the Arm: single GamTBvac vaccination (0.25 dose). | Biological: Single GamTBvac vaccination (0.25 dose)<br>* Single administration of the decreased dose of vaccine (0.25 of regular dose) to evaluate the safety.<br>|
| Placebo Comparator: Placebo safety study group<br>12 persons who have got a single dose of placebo (0.5 ml). The intervention for the Arm: Placebo administration (0.5 ml) | Biological: Placebo administration<br>* Single administration of the placebo (0.5 ml) to a placebo safety study group (Arm 2).<br>|
| Experimental: Immunogenicity study group #1<br>12 persons who will get a double sequential administration of the decreased dose (0.25 of the planned dose for regular applying) of the GamTBvac recombinant subunit vaccine. The intervention for the Arm: double GamTBvac vaccination (0.25 dose). | Biological: Double GamTBvac vaccination (0.25 dose)<br>* Double sequential administration of the decreased dose of vaccine (0.25 of regular dose) to evaluate the immunogenicity.<br>|
| Experimental: Immunogenicity study group #2<br>12 persons who will get a double sequential administration of the mean dose (0.5 of the planned dose for regular applying) of the GamTBvac recombinant subunit vaccine. The intervention for the Arm: double GamTBvac vaccination (0.5 dose). | Biological: Double GamTBvac vaccination (0.5 dose)<br>* Double sequential administration of the mean dose of vaccine (0.5 of regular dose) to evaluate the immunogenicity.<br>|
| Experimental: Immunogenicity study group #3<br>12 persons who will get a double sequential administration of the maximum (regular) dose of the GamTBvac recombinant subunit vaccine. The intervention for the Arm: double GamTBvac vaccination (1.0 dose). | Biological: Double GamTBvac vaccination (1.0 dose)<br>* Double sequential administration of the regular dose of vaccine to evaluate the immunogenicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and severity of adverse effects | Safety control: an active periodical examination of the health status of volunteers, including vital indicators, instrumental tests (ECG), laboratory blood and urine analysis (general and biochemistry). The presence, nature and severity of local and systemic reactions in different groups of volunteers, depending on the dose of vaccination, will be taken into account. | 140 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunogenicity control | Qualitative ELISA test for specific IgG antibodies, study of the stimulated T-cell | 140 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, Recombinant vaccine, Mycobacterium tuberculosis