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

NCT04975737 | Active Not Recruiting Phase 3

• 1 other identifier: 02-GamTBvac-2020
• Study Type: interventional
• Target: 9,500
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (6)

Vaccine Group (Stage 1)

EXPERIMENTAL

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

Placebo group (Stage 1)

PLACEBO COMPARATOR

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

Vaccine Group (Stage 2)

EXPERIMENTAL

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

Placebo group (Stage 2)

PLACEBO COMPARATOR

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

Vaccine Group (Stage 3)

EXPERIMENTAL

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

Placebo group (Stage 3)

PLACEBO COMPARATOR

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

Interventions

GamTBvac BIOLOGICAL

The subunit recombinant tuberculosis vaccine GamTBvac (lyophilisate for preparation of solution for subcutaneous administration, 5.35 mg / dose)

Vaccine Group (Stage 1); Vaccine Group (Stage 2); Vaccine Group (Stage 3)

Placebo BIOLOGICAL

Placebo for subcutaneous administration

Placebo group (Stage 1); Placebo group (Stage 2); Placebo group (Stage 3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female volunteers aged ≥ 18 years.
• Absence of active tuberculosis, confirmed by chest X ray or chest computed tomography (CT), clinical evaluation, and laboratory findings.
• For the purpose of additional safety evaluations of the investigational product in Stage I: no history of active respiratory tuberculosis.
• 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.
• For the purpose of the primary efficacy and safety evaluations in Stage III: no history of active respiratory tuberculosis.
• Body mass index (BMI) 18.5 - 30 kg/m² (inclusive), calculated as weight/height² (Quetelet index).
• Written informed consent obtained from the volunteer to participate in the study in accordance with applicable laws and regulations.
• Prior BCG vaccination, as documented in the medical records or confirmed by the presence of a BCG scar.
• Negative pregnancy test for female volunteers of childbearing potential at screening and on the day of first vaccination.
• 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).
• 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.
• 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);
• History of extrapulmonary tuberculosis, with the exception of bronchial tuberculosis;
• 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;

You may not qualify if:

• Participation of a volunteer in the study may be terminated for the following reasons:
• Development of tuberculosis of any localization, including respiratory tuberculosis, or recurrence of respiratory tuberculosis.
• The investigator determines that the volunteer should be withdrawn in the volunteer's best interest.
• Occurrence of a serious adverse event (SAE) related to the investigational vaccine.
• Non-compliance by the volunteer with the study participation requirements.
• Retusal to cooperate or non-compliance by the participant.
• Development of any other significant adverse events.
• Deterioration of the volunteer's health status.
• Initiation of another investigational product by the volunteer.
• Major protocol violations that may affect the volunteer's safety or the integrity of the study data.

Sponsors & Collaborators

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

Study Sites (1)

City hospital #40

Saint Petersburg, 197706, Russia

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 23, 2021
• Study Start: January 20, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 6, 2026

Record last verified: 2026-06

Locations

RU (1)