Study of the Safety and Efficacy of the Subunit Recombinant Tuberculosis Vaccine GamTBvac

A Multicenter, Double-blind, Randomized, Placebo-controlled Study of the Safety and Efficacy of the GamTBvac Recombinant Subunit Tuberculosis Vaccine for the Prevention of Non-HIV-associated Pulmonary Tuberculosis in Volunteers Aged 18 Years and Older.

This study is a multicenter, double-blind, randomized, placebo-controlled Phase III trial designed to evaluate the efficacy and safety of the GamTBvac recombinant subunit tuberculosis vaccine for the prevention of active non-HIV-associated pulmonary tuberculosis.

The study is divided into three stages. A total of 9,500 volunteers are planned to be enrolled in the study.

Stage 1: A total of 354 volunteers with no history of pulmonary tuberculosis will be enrolled. Volunteers will be randomized in a 1:1 ratio into one of two groups receiving either GamTBvac or placebo. Within each group, stratification will be performed according to the presence or absence of a risk factor (smoking). Based on the results of this stage, the safety of the GamTBvac vaccine will be evaluated according to the criteria specified in the study objectives for Stage 1.

Stage 2: A total of 2,146 volunteers with a history of active pulmonary tuberculosis that resulted in cure without residual changes or with minor residual changes, without aggravating factors, and who at the time of participation are registered and under follow-up in Dispensary Group III will be enrolled. Volunteers will be randomized in a 1:1 ratio into one of two groups receiving either GamTBvac or placebo. Based on the results of this stage, the prophylactic efficacy and safety of the GamTBvac vaccine will be evaluated according to the criteria specified in the study objectives for Stage 2.

In the absence of statistically significant data on vaccine efficacy by Visit 6 (24 months ± 30 days), the study will proceed to Stage 3. In the event that statistically significant data on the prophylactic efficacy of GamTBvac are obtained by Visit 6 (24 months ± 30 days), the study will be terminated.

Stage 3: Up to 7,000 volunteers with no history of active pulmonary tuberculosis will be enrolled. Volunteers will be randomized in a 1:1 ratio into one of two groups receiving either GamTBvac or placebo. Within each group, stratification will be performed according to the presence or absence of a risk factor (smoking). Based on the results of this stage, the safety and prophylactic efficacy of the GamTBvac vaccine will be evaluated according to the criteria specified in the study objectives for Stage 3.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: GamTBvac; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 9500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russia
  • Saint Petersburg, Russia, 197706
    • City hospital #40

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female volunteers aged ≥ 18 years.
2. Absence of active tuberculosis, confirmed by chest X ray or chest computed tomography (CT), clinical evaluation, and laboratory findings.
3. For the purpose of additional safety evaluations of the investigational product in Stage I: no history of active respiratory tuberculosis.
4. For the purpose of the primary and secondary efficacy and safety evaluations in Stage II: a history of active respiratory tuberculosis with documented cure, with no residual changes or only minor residual changes without aggravating factors, and the volunteer must have been transferred to and remain under Group III dispensary follow up (clinical Group III*) for tuberculosis at the time of study enrollment.
5. For the purpose of the primary efficacy and safety evaluations in Stage III: no history of active respiratory tuberculosis.
6. Body mass index (BMI) 18.5 - 30 kg/m² (inclusive), calculated as weight/height² (Quetelet index).
7. Written informed consent obtained from the volunteer to participate in the study in accordance with applicable laws and regulations.
8. Prior BCG vaccination, as documented in the medical records or confirmed by the presence of a BCG scar.
9. For volunteers without a history of active pulmonary tuberculosis: negative immune response markers to mycobacterial proteins ESAT 6 and CFP 10 (indicating no prior probable contact with M. tuberculosis before study entry), as assessed by Diaskintest® and Mantoux test. For volunteers with a history of active respiratory tuberculosis that has resolved with cure and no residual or only minor residual changes without aggravating factors, and who are under Group III dispensary follow up at the time of enrollment, testing for ESAT 6/CFP 10 immune markers is not an inclusion/exclusion criterion.
10. Negative pregnancy test for female volunteers of childbearing potential at screening and on the day of first vaccination.
11. Agreement by male participants and female participants of childbearing potential to use adequate contraception (dual barrier method: male or female condom combined with hormonal contraception [oral, vaginal, or transdermal], or use of a condom or diaphragm with spermicide) throughout the entire vaccination period and for 1 month after the last vaccination. Exceptions: surgically sterile individuals (for > 6 months) or postmenopausal individuals (for > 12 months).

12. Agreement by male participants to refrain from sperm donation throughout the entire vaccination period and for 1 month after the last vaccination.

    • According to the Russian tuberculosis clinical classification, Group III dispensary registration applies to individuals cured of tuberculosis who are at low risk of relapse and require regular follow-up monitoring.

Non-inclusion criteria:

1. Positive test results for HIV-1/2 antibodies, HBsAg, or hepatitis C virus antibodies at screening (results obtained no later than 30 days prior to study enrollment may be used);
2. History of extrapulmonary tuberculosis, with the exception of bronchial tuberculosis;
3. History of chronic non-infectious respiratory diseases, including idiopathic pulmonary fibrosis (IPF), bronchial asthma, severe or very severe chronic obstructive pulmonary disease (COPD), or pulmonary hypertension;
4. Presence of family contact with a tuberculosis patient at the time of the study;
5. Incarceration in a penal institution within 24 months prior to study enrollment;
6. Clinically significant ECG abnormalities at screening;
7. History of significant allergic conditions (bronchial asthma, history of anaphylactic reactions);
8. Hypersensitivity to any component of the investigational product or placebo; history of drug intolerance;
9. Presence of any disease or use of any medication that, in the investigator's opinion, may interfere with the assessment of vaccine safety or efficacy;
10. History or physical/laboratory findings suggestive of any possible immunodeficiency condition;
11. History of any autoimmune disease (including systemic lupus erythematosus, type 1 diabetes mellitus, etc.);
12. Regular use (for more than 2 weeks) of immunosuppressants or other immunomodulating drugs within 6 months prior to the study enrollment (with the exception of inhaled or topical corticosteroids);
13. Use of immunoglobulin or blood products within 3 months prior to or planned use during the study enrollment;
14. Use of antibacterial (including anti-tuberculosis) drugs within 14 days prior to vaccination orally and/or within 28 days prior to vaccination (parenterally);
15. Pregnancy, breastfeeding, refusal to use a double-barrier method of contraception, participation of a woman in an oocyte donation program;
16. Inability of the volunteer to understand the objectives, goals, and design of the study; known inability to comply with the protocol-specified plan, visit schedule, and procedures;
17. Participation in clinical trials of medicinal products within 3 months prior to the study enrollment, or planned participation in another clinical trial;
18. Previous receipt of the GamTBvac vaccine and/or participation in clinical trials of any experimental anti-tuberculosis vaccines;
19. Any vaccination or planned vaccination within less than one month prior to the first vaccination in this study or within one month after each vaccination in this study;
20. Confirmed history of alcoholism, drug addiction, or substance abuse;
21. Positive urine drug test for narcotic and psychotropic substances;
22. Positive ethanol test (in exhaled breath)/using saliva test strips.

Exclusion Criteria:

Participation of a volunteer in the study may be terminated for the following reasons:

1. Development of tuberculosis of any localization, including respiratory tuberculosis, or recurrence of respiratory tuberculosis.
2. The investigator determines that the volunteer should be withdrawn in the volunteer's best interest.
3. Occurrence of a serious adverse event (SAE) related to the investigational vaccine.
4. Non-compliance by the volunteer with the study participation requirements.
5. Retusal to cooperate or non-compliance by the participant.
6. Enrollment of the participant in violation of the protocol's inclusion/non-inclusion criteria.
7. Development of any other significant adverse events.
8. Deterioration of the volunteer's health status.
9. Initiation of another investigational product by the volunteer.
10. Major protocol violations that may affect the volunteer's safety or the integrity of the study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccine Group (Stage 1); 177 volunteers will be receiving GamTBvac. Subcutaneous administration of the vaccine will be performed at Vaccination Visits No. 1 and No. 3 (Day 1 and Day 57 ± 1) in an outpatient setting. After each vaccination, participants will be observed for 5 hours. Subsequent follow-up visits are planned as follows: Visit 2 (Day 7 ± 1), Visit 4 (Day 64 ± 1), Visit 5 (12 months ± 14 days), and Visit 6 (24 months ± 30 days).	Biological: GamTBvac; The subunit recombinant tuberculosis vaccine GamTBvac (lyophilisate for preparation of solution for subcutaneous administration, 5.35 mg / dose)
Placebo Comparator: Placebo group (Stage 1); 177 volunteers will be receiving placebo. Subcutaneous administration of the placebo will be performed at Vaccination Visits No. 1 and No. 3 (Day 1 and Day 57 ± 1) in an outpatient setting. After each administration, participants will be observed for 5 hours. Subsequent follow-up visits are planned as follows: Visit 2 (Day 7 ± 1), Visit 4 (Day 64 ± 1), Visit 5 (12 months ± 14 days), and Visit 6 (24 months ± 30 days).	Biological: Placebo; Placebo for subcutaneous administration
Experimental: Vaccine Group (Stage 2); 1073 volunteers with a history of active pulmonary tuberculosis that resulted in cure without residual changes or with minor residual changes, without aggravating factors, and who at the time of participation are registered and under follow-up in Dispensary Group III will be receiving GamTBvac. Subcutaneous administration of GamTBvac will be performed at Vaccination Visits No. 1 and No. 3 (Day 1 and Day 57 ± 1) in an outpatient setting. Participants will be observed for 5 hours after each vaccination. Follow-up visits are planned as follows: Visit 2 (Day 7 ± 1), Visit 4 (Day 64 ± 1), Visit 5 (12 months ± 14 days), and Visit 6 (24 months ± 30 days). In addition, between Visit 5 and Visit 6, the investigator will contact participants by telephone once every 3 months (± 14 days) to assess their well-being and to record adverse events and concomitant therapy.	Biological: GamTBvac; The subunit recombinant tuberculosis vaccine GamTBvac (lyophilisate for preparation of solution for subcutaneous administration, 5.35 mg / dose)
Placebo Comparator: Placebo group (Stage 2); 1073 volunteers with a history of active pulmonary tuberculosis that resulted in cure without residual changes or with minor residual changes, without aggravating factors, and who at the time of participation are registered and under follow-up in Dispensary Group III will be receiving placebo. Subcutaneous administration of placebo will be performed at Vaccination Visits No. 1 and No. 3 (Day 1 and Day 57 ± 1) in an outpatient setting. Participants will be observed for 5 hours after each administration. Follow-up visits are planned as follows: Visit 2 (Day 7 ± 1), Visit 4 (Day 64 ± 1), Visit 5 (12 months ± 14 days), and Visit 6 (24 months ± 30 days). In addition, between Visit 5 and Visit 6, the investigator will contact participants by telephone once every 3 months (± 14 days) to assess their well-being and to record adverse events and concomitant therapy.	Biological: Placebo; Placebo for subcutaneous administration
Experimental: Vaccine Group (Stage 3); 3500 volunteers with no history of active pulmonary tuberculosis will be receiving GamTBvac. Subcutaneous administration of the vaccine will be performed at Vaccination Visits No. 1 and No. 3 (Day 1 and Day 57 ± 1) in an outpatient setting. After each vaccination, participants will be observed for 5 hours. Subsequent follow-up visits are planned as follows: Visit 2 (Day 7 ± 1), Visit 4 (Day 64 ± 1), Visit 5 (12 months ± 14 days), and Visit 6 (24 months ± 30 days). In addition, between Visit 5 and Visit 6, the investigator will contact participants by telephone once every 3 months (± 14 days) to assess their well-being and to record adverse events and concomitant therapy.	Biological: GamTBvac; The subunit recombinant tuberculosis vaccine GamTBvac (lyophilisate for preparation of solution for subcutaneous administration, 5.35 mg / dose)
Placebo Comparator: Placebo group (Stage 3); 3500 volunteers with no history of active pulmonary tuberculosis will be receiving placebo. Subcutaneous administration of the placebo will be performed at Vaccination Visits No. 1 and No. 3 (Day 1 and Day 57 ± 1) in an outpatient setting. After each administration, participants will be observed for 5 hours. Subsequent follow-up visits are planned as follows: Visit 2 (Day 7 ± 1), Visit 4 (Day 64 ± 1), Visit 5 (12 months ± 14 days), and Visit 6 (24 months ± 30 days). In addition, between Visit 5 and Visit 6, the investigator will contact participants by telephone once every 3 months (± 14 days) to assess their well-being and to record adverse events and concomitant therapy.	Biological: Placebo; Placebo for subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy assessment - Stage 1	Efficacy will be assessed in volunteers aged 18 years and older. All study participants will be informed of the potential signs and symptoms indicative of pulmonary tuberculosis and will be instructed to report to the study site promptly should any such symptoms develop, in order to undergo an Unscheduled Visit. For Stage 1, the primary efficacy endpoint will be the incidence rate of respiratory tuberculosis. The diagnosis will be confirmed by the presence of pulmonary foci or infiltrations (physiological parameter) as determined by chest radiography (diagnostic test).	24 months after vaccination
Primary endpoint for Stage 2 of the study	The prophylactic efficacy of the GamTBvac vaccine will be assessed by comparing the incidence rate of active pulmonary tuberculosis cases between the study groups during the post-vaccination follow-up period in volunteers with a prior history of active respiratory tuberculosis, at 24 month after the first vaccination.	24 months after vaccination
Primary endpoint for Stage 3 of the study	The prophylactic efficacy of the GamTBvac vaccine will be assessed by comparing the incidence rate of active pulmonary tuberculosis cases between the study groups during the post-vaccination follow-up period in volunteers with no prior history of active respiratory tuberculosis, at 24 months after the first vaccination.	24 months after vaccination
Safety Endpoint Analysis	Safety analyses will be performed in the safety population (SAF). The number and percentage of volunteers with adverse events (AEs) and serious adverse events (SAEs) will be tabulated by system organ class (SOC) and preferred term (PT) according to the MedDRA dictionary, by relationship to the investigational product.	24 months after the vaccination

Collaborators and Investigators

• Sponsor: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: 02-GamTBvac-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No