Phase 2 Study of the ТВ/Flu-05Е Tuberculosis Vaccine

Randomized, Double-blind, Placebo-controlled Phase 2 Trial of ТВ/Flu-05Е Intranasal Vector Vaccine for the Prevention of Tuberculosis Infection in BCG-vaccinated Volunteers Aged 18-50 Years

The aim of the study is to investigate immunogenicity and safety of the TB/Flu-05E single-dose intranasal vaccine for the prevention of Tuberculosis infection in BCG-vaccinated Volunteers aged 18-50 years

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Biological: TB/Flu-05E; Other: Placebo

Detailed Description

Study includes 160 participants aged 18 to 50, randomized at 3:1 ratio, to receive single intranasal dose of TB/Flu-05E vaccine or placebo, correspondingly. Duration of the study for each participant is about 4 months (no more than 114 days).

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • St Petersburg, Russian Federation, 197022
    • Smorodintsev Research Institute of Influenza
  • St. Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • St. Petersburg, Russian Federation, 197198
    • St. Petersburg City Polyclinic No. 34

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy BCG-vaccinated men and women aged 18 to 50 years
2. Availability of signed informed consent
3. Diagnosed "healthy" according to the data of standard clinical, laboratory and instrumental examination methods, with the absence of clinically significant changes. Participants with chronic conditions that do not require special treatment, such as diabetes mellitus, hypertension, or heart disease, are eligible to participate in this study if the investigator considers the participant's condition to be medically stable
4. The ability and willingness to make entries in the diary of self-observation, as well as to carry out all the visits foreseen in the study for control medical observation

5. Consent of study participants to use effective contraceptive methods throughout their participation in the study. In this study, volunteers can use the following methods of contraception:

   • Barrier methods:

     • male condom and spermicide
     • cervical cap and spermicide
     • vaginal diaphragm and spermicide
   • Intrauterine device
   • Hormonal intrauterine device

   • Hormonal contraceptives:

     • hormonal implants
     • hormone injections
     • combined oral contraceptives
     • mini-pill
     • contraceptive patch
   • Abstinence from sexual activity.
6. Body weight ≥ 50 kg
7. Negative test for alcohol in exhaled air
8. Values of the complete blood count and biochemical blood analysis (during the screening) within 0.9*reference range lower limit and 1,1 * reference range upper limit
9. Negative tests for HIV, hepatitis B, hepatitis C, and syphilis
10. Absence of pathological changes on the chest X-ray (fluorogram of the lungs).

Exclusion Criteria:

1. Participation in another clinical study within three months prior to the start of the current study; planning to participate in another study during the current study period
2. Clinical, radiological or laboratory signs of active or previously transferred tuberculosis of any localization.
3. Existence in the past or present of contact with patients with any form of tuberculosis (at home, at work, in the circle of friends and acquaintances)
4. Tuberculous infection confirmed by the TB-FERON IGRA laboratory test
5. Immunization with BCG within six months prior to enrollment in the current study
6. Contact with COVID-19 patients within 14 days prior to the start of the clinical study
7. Positive rapid test result for SARS-CoV-2 antigen
8. Immunization with any other non-study vaccine product within three weeks prior to enrollment in the current study, or refusal to postpone such until the end of the three-week period after completion of the current study
9. Regular use of nasal irrigation therapy during the last six months prior to enrollment in the current study or episodic use of the above method of treatment in the two weeks prior to the screening
10. History of frequent nosebleeds (>5) during the year prior to the current study
11. Features of the nasal anatomy that may complicate intranasal administration of the study drug.
12. Surgical interventions or traumatic injuries in the sinus area, paranasal sinuses, or traumatic injuries of the nose within a month before screening
13. Symptoms of acute respiratory disease, including fever, or other acute illness at the time of screening or within two weeks prior to screening
14. Treatment with immunoglobulins or other blood derived medications in the three months prior to screening or planning such treatment during the period of participation in the current study
15. History of bronchial asthma
16. Hypersensitivity and the presence of severe allergic reactions, including Quincke's edema, anaphylactic shock after the previous administration of any vaccine
17. History of wheezing after previous immunization with live influenza vaccine
18. Other adverse events after immunization (fever above 40°C, syncope, non-febrile convulsions, anaphylaxis) when there is a minimal likelihood that they are associated with a previous administration of any vaccine
19. Suspicion of hypersensitivity to any component of the study vaccine, including egg protein
20. Acute or chronic clinically significant lung, cardiovascular, hepatic, endocrine, neurological, or psychiatric disorders, or impaired renal function identified by history, physical examination, or clinical laboratory findings that, in the opinion of the investigator, may influence the outcome of the study
21. History of oncological diseases
22. History of thrombocytopenic purpura or bleeding disorders
23. History of convulsions
24. Chronic alcohol dependence or chronic use of illicit drugs, drug abuse
25. Claustrophobia and social phobia according to history and / or available medical records
26. Inability to read Russian; inability or unwillingness to understand the essence of the study
27. Military personnel undergoing military service on conscription
28. Special diet (eg, vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical activity)
29. Any condition that, in the opinion of the investigator, may increase the risk to the health of a volunteer participating in the study or affect the results of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single dose of Placebo	Other: Placebo; Participants will receive single intranasal injection of physiological buffer in 0.5 ml
Experimental: TB/Flu-05E; Single dose of TB/Flu-05E vector vaccine	Biological: TB/Flu-05E; Participants will receive single intranasal injection of TB/Flu-05E vaccine in 0.5 ml, containing 7.7 lg EID50 of A/H1N1pdm09 recombinant attenuated influenza vector with modified NS gene, encoding for the TB10.4 and HspX antigens of M. tuberculosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of TB antigen-specific cytokine producing T-cells	Change from baseline in the level of cytokine producing T-cells upon in vitro stimulation of PBMC with M. tuberculosis peptide epitopes (TB10.4, HspX) measured by FACS/ELISPOT	Days 1, 7, 21
Level of TB antigen-specific cytokine release in whole blood assay	Change from the baseline of the cytokine concentration in whole-blood cytokine release assay upon in vitro stimulation with M. tuberculosis peptide epitopes (TB10.4, HspX) measured in ELISA	Days 1, 7, 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs)	Adverse events (AEs) and serious AEs (SAEs), both vaccine related, and non-vaccine related. AEs/SAEs of particular importance: - Immediate AEs (allergic reactions) occurring within two hours of vaccination; - Post-vaccination reactions (anticipated clinical manifestations of a local and systemic nature), usually due to intranasal vaccination between two hours and the next 7 days after vaccination	Throughout the study, average 4 months
Percent of participants with T-cell response to M. tuberculosis antigens	Relative number of participants with T-cell response to the M. tuberculosis antigens (TB10.4 or HspX) in any of the tests (FACS/ELISPOT, whole blood cytokine release assay) at any of the study days	Days 7, 21
Level of TB antigen-specific IgG antibody in serum	Change from the baseline in the level of TB10.4 and HspX specific IgG antibody measured in ELISA in serum	Days 1, 21, 111±3
Level of B-cell and Tfh-cell populations	Change from the baseline in the relative amount of B-cell and Tfh-cell populations measured by FACS	Days 1, 7, 21
Level of mucosal IgA antibody in nasal secret	Change from the baseline in the level of IgA antibody measured in ELISA in nasal secret	Days 1, 21
Level of influenza-specific cytokine producing T-cells	Change from baseline in the level of cytokine producing T-cells upon in vitro stimulation of PBMC with influenza antigen measured by ICS/ELISPOT	Days 1, 7, 21
Influenza specific systemic antibody immune response	Change from baseline in the titer of influenza specific antibodies in serum measured in hemagglutination inhibition/microneutralization assay	Days 1, 21, 111±3

Collaborators and Investigators

• Sponsor: Research Institute of Influenza, Russia
• Collaborators: Pavlov First Saint Petersburg State Medical University; St. Petersburg City Polyclinic No. 34
• Investigators: Study Director: Marina Stukova, Dr, Smorodintsev Research Institute of Influenza

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Actual): January 12, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Tuberculosis vaccine; influenza vector; BCG boost; mucosal vaccine
• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: ВПТ-2-06/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only IPD used in the results publication will be available
• IPD Sharing Access Criteria: IPD will be available upon reasonable request to Study Director. Once the request is approved, the data can be transferred via a secure online platform

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No