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

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.

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: 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)

Detailed 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 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:

1. 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);
2. 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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119435
    • Sechenov First Moscow State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety and portable study group; 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); Single administration of the decreased dose of vaccine (0.25 of regular dose) to evaluate the safety.
Placebo Comparator: Placebo safety study group; 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; Single administration of the placebo (0.5 ml) to a placebo safety study group (Arm 2).
Experimental: Immunogenicity study group #1; 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); Double sequential administration of the decreased dose of vaccine (0.25 of regular dose) to evaluate the immunogenicity.
Experimental: Immunogenicity study group #2; 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); Double sequential administration of the mean dose of vaccine (0.5 of regular dose) to evaluate the immunogenicity.
Experimental: Immunogenicity study group #3; 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); Double sequential administration of the regular dose of vaccine to evaluate the immunogenicity.

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Tkachuk AP, Gushchin VA, Potapov VD, Demidenko AV, Lunin VG, Gintsburg AL. Multi-subunit BCG booster vaccine GamTBvac: Assessment of immunogenicity and protective efficacy in murine and guinea pig TB models. PLoS One. 2017 Apr 28;12(4):e0176784. doi: 10.1371/journal.pone.0176784. eCollection 2017.

Helpful Links

• Tkachuk AP, Gushchin VA, Potapov VD, Demidenko AV, Lunin VG, Gintsburg AL. Multi-subunit BCG booster vaccine GamTBvac: Assessment of immunogenicity and protective efficacy in murine and guinea pig TB models. PLoS One. 2017 Apr 28

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2017
• Primary Completion (Actual): December 13, 2017
• Study Completion (Actual): December 13, 2017

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 27, 2017
• Last Update Submitted That Met QC Criteria: December 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Tuberculosis; Mycobacterium tuberculosis; Recombinant vaccine
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: GamTBvac Ph1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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