Using BCG Vaccine to Understand Tuberculosis Infection

NCT05820594 | Unknown DMC

• 2 other identifiers: 23-005321376
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) is a disease that usually causes an infection in the lungs. The only vaccine to prevent TB is called BCG (Bacillus Calmette-Guérin). BCG contains a live germ similar to Mycobacterium tuberculosis, the germ that causes TB. BCG does not work very well, and TB remains the most common cause of death by infection worldwide. Human challenge models involve exposing healthy volunteers to an infectious disease in a safe and controlled way. This helps researchers understand more about an infectious disease and the body's response and can help develop new vaccines and treatments. The purpose of this study is to set up a human challenge model using BCG to understand how the body responds to this. If our human challenge model works well it may be used to help researchers develop new vaccines and tablets to treat TB in the future. This study will recruit healthy volunteers, of all genders, age 18-50 years. The first part of the study (phase A) will recruit 10 participants. Participants in phase A will receive intradermal injection with BCG into the upper arm at three times the usual dose. On day 14 after BCG the following skin samples will be taken from the BCG site with the use of local anaesthetic: skin swab, microbiopsy, skin scrape and punch biopsy. Participants in this phase of the study will also have blood tests to ensure they are safe to take part and to monitor the immune response to BCG. The overall aim of this part of the study will be to ensure BCG can be isolated (grown in culture and by molecular techniques) from participants' BCG site 14 days after the injection. The investigators aim to test whether BCG can be isolated by punch biopsy and minimally invasive techniques (microbiopsy, skin scrape and skin swab). If the investigators find that they can isolate BCG successfully using the minimally invasive methods of skin sampling and the participants have not experienced any serious adverse events, they can proceed to phase B of the study. In phase B 20 participants will be recruited. These participants will receive BCG as described for phase A. They will then have serial skin samples taken using either microbiopsy, skin scrape or skin swab on days 0, 2, 7, 14 and 28. The focus of this phase of the study is to assess immune responses to intradermal injection at the local (skin), systemic (blood) and respiratory mucosal (nose) compartments. This will involve longitudinal sampling from blood, nose and skin to measure BCG growth and the immune response over time.

Conditions

Tuberculosis

Keywords

BCG; bacille calmette-guérin; Human challenge; Controlled human infection

Outcome Measures

Primary Outcomes (1)

• To quantify BCG recovered from the intradermal BCG challenge site.

  Culture and PCR quantification of BCG at intradermal challenge site by punch biopsy at day 14, Phase A.

  Day 14 (post BCG injection), phase A.

Secondary Outcomes (9)

• To monitor for adverse events and any serious adverse events in participants

  Daily symptom diary for 14 days, clinic review on day 2, 7, 14, 21 and 28 post BCG injection

• Confirm agreement between BCG recovery between punch biopsy and minimally invasive skin biopsy.

  Day 14, phase A.

• Confirm agreement between BCG recovery between punch biopsy and minimally invasive skin scrape.

  Day 14, phase A.

• Longitudinal quantification of BCG recovery from the intradermal BCG challenge site.

  Day 2, 7, 14, 21, 28, Phase B

• Evaluate the immune response to BCG at intradermal injection site from skin biopsy

  Day 2, 7, 14, 21, 28, Phase B.

Study Arms (1)

Intradermal injection with BCG SSI

EXPERIMENTAL

Intradermal injection with BCG (bacillus calmette-guerin) vaccine at day 0.

Biological: Intradermal BCG (bacillus calmette-guerin) vaccine AJV

Interventions

Intradermal BCG (bacillus calmette-guerin) vaccine AJV BIOLOGICAL

Participants will receive a one off dose of BCG (bacillus calmette-guerin) Vaccine AJV which contains the Danish Strain of Mycobacterium bovis BCG at a dose of 6 - 24 x 105 CFU (three times the standard dose). This will be injected intradermally into the upper deltoid region.

Intradermal injection with BCG SSI

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Resident near LSTM (\<1hr drive) for the duration of the study period
• Allows the investigators to discuss the volunteer's medical history with their GP
• Females of childbearing potential with a negative urine pregnancy test at screening and willing to practice adequate birth control measures during the study.
• Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement
• Capacity to provide written informed consent
• Able and willing (in the investigators opinion) to comply with all the study requirements

You may not qualify if:

• Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
• Clinical, radiological, or laboratory evidence of current active TB disease
• Previous vaccination with BCG, or any candidate TB vaccine
• Within the last year had close household contact with an individual with smear positive pulmonary tuberculosis
• Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer, cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness or psychiatric disorder.
• Current medical issues
• Acute respiratory tract infection in the four weeks preceding recruitment
• Any uncontrolled medical or surgical condition at the discretion of the study doctor
• Maternal
• Female participants who are pregnant
• Female participants who are lactating
• Female participants who intend to become pregnant during the study
• Female participants who are unable to take contraception measures during the study
• Smoking
• Current (defined as ≥5/week) or ex-smoker (cigarettes / cigars / e-cigarette / vaping / smoking of recreational drugs) in the last 6 months.

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead
• University of Oxford: collaborator

Study Sites (1)

Liverpool School of Tropical Medicine

Liverpool, L3 5QA, United Kingdom

RECRUITING

Related Publications (4)

• Minassian AM, Ronan EO, Poyntz H, Hill AV, McShane H. Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy. PLoS One. 2011;6(5):e19840. doi: 10.1371/journal.pone.0019840. Epub 2011 May 24.

  PMID: 21629699 BACKGROUND

• Minassian AM, Satti I, Poulton ID, Meyer J, Hill AV, McShane H. A human challenge model for Mycobacterium tuberculosis using Mycobacterium bovis bacille Calmette-Guerin. J Infect Dis. 2012 Apr 1;205(7):1035-42. doi: 10.1093/infdis/jis012.

  PMID: 22396610 BACKGROUND

• Harris SA, Meyer J, Satti I, Marsay L, Poulton ID, Tanner R, Minassian AM, Fletcher HA, McShane H. Evaluation of a human BCG challenge model to assess antimycobacterial immunity induced by BCG and a candidate tuberculosis vaccine, MVA85A, alone and in combination. J Infect Dis. 2014 Apr 15;209(8):1259-68. doi: 10.1093/infdis/jit647. Epub 2013 Nov 23.

  PMID: 24273174 BACKGROUND

• Carter E, Morton B, ElSafadi D, Jambo K, Kenny-Nyazika T, Hyder-Wright A, Chiwala G, Chikaonda T, Chirwa AE, Gonzalez Sanchez J, Yip V, Biagini G, Pennington SH, Saunderson P, Farrar M, Myerscough C, Collins AM, Gordon SB, Ferreira DM. A feasibility study of controlled human infection with intradermal Bacillus Calmette-Guerin (BCG) injection: Pilot BCG controlled human infection model. Wellcome Open Res. 2024 Jun 5;8:424. doi: 10.12688/wellcomeopenres.19811.2. eCollection 2023.

  PMID: 39219857 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Ben Morton, MD. MPH, MBChB

  Liverpool School of Tropical Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ben Morton, MD, MPH, MBChB

CONTACT

+44 (0)151 705 3295; ben.morton@lstmed.ac.uk

Emma Carter, MBBS

CONTACT

+44 (0)151 702 9455; emma.carter@lstmed.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single centre, prospective longitudinal controlled human infection study after intradermal injection with BCG SSI

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 19, 2023
• Study Start: June 30, 2023
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: July 7, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: At the end of study
• Access Criteria: Data may be shared on suitable direct request from individual researchers to the chief investigator.

Locations

GB (1)