Aerosol BCG Challenge Study in Historically BCG-vaccinated Volunteers

NCT04777721 | Completed Phase 1 Results

• 1 other identifier: TB044
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the human clinical response to BCG challenge in historically BCG-vaccinated healthy adult volunteers. It will involve 12 participants in a controlled dose escalation. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.

Conditions

Tuberculosis

Keywords

Tuberculosis; BCG; Human challenge; Aerosol BCG challenge

Outcome Measures

Primary Outcomes (1)

• To Quantify BCG Recoverable From Bronchial Sample

  Quantification of BCG culture by mycobacterial growth indicator tube (PCR quantification and DNA strip assay speciation as required)

  Day 14

Secondary Outcomes (1)

• Adverse Events

  Up to day 168

Other Outcomes (6)

• Identify Laboratory Markers of Immune Response That Correlate With the Levels of BCG Recovered From Bronchial and Other Samples.

  Up to day 168

• Identify Laboratory Markers of Immune Response That Correlate With the Levels of BCG Recovered From Bronchial Samples.

  Up to day 168

• Identify Laboratory Markers of Immune Response That Correlate With the Levels of BCG Recovered From Bronchial Samples.

  Up to day 168

Study Arms (4)

Group 1: 1 x 10^4 cfu aerosol inhaled BCG

EXPERIMENTAL

3 historically BCG-vaccinated volunteers will receive 1 x 10\^4 cfu aerosol inhaled BCG. All Group 1 volunteers will have a bronchoscopy 14 days post challenge.

Biological: BCG Danish

Group 2: 1 x 10^5 cfu aerosol inhaled BCG

EXPERIMENTAL

3 historically BCG-vaccinated volunteers will receive 1 x 10\^5 cfu aerosol inhaled BCG. All Group 2 volunteers will have a bronchoscopy 14 days post challenge.

Biological: BCG Danish

Group 3: 1 x 10^6 cfu aerosol inhaled BCG

EXPERIMENTAL

3 historically BCG-vaccinated volunteers will receive 1 x 10\^6 cfu aerosol inhaled BCG. All Group 3 volunteers will have a bronchoscopy 14 days post challenge.

Biological: BCG Danish

Group 4: 1 x 10^7 cfu aerosol inhaled BCG

EXPERIMENTAL

3 historically BCG-vaccinated volunteers will receive 1 x 10\^7 cfu aerosol inhaled BCG. All Group 3 volunteers will have a bronchoscopy 14 days post challenge.

Biological: BCG Danish

Interventions

BCG Danish BIOLOGICAL

BCG Danish 1331 is on the WHO list of pre-qualified vaccines and has a well-defined side effect profile. BCG is licensed for delivery via the intradermal route. It is not licensed for delivery via the aerosol route.

Group 1: 1 x 10^4 cfu aerosol inhaled BCG; Group 2: 1 x 10^5 cfu aerosol inhaled BCG; Group 3: 1 x 10^6 cfu aerosol inhaled BCG; Group 4: 1 x 10^7 cfu aerosol inhaled BCG

Eligibility Criteria

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

You may qualify if:

• Healthy adults aged 18-50 years
• Previously vaccinated with the BCG (at least 6 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records)
• Resident in or near Oxford for the duration of the study period
• Provide written informed consent
• Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner (or review summary care record, if available)
• Allow the investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials
• Agreement to refrain from blood donation during the course of the study
• For women of child-bearing potential only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, challenge and bronchoscopy
• Able and willing (in the investigator's opinion) to comply with all study requirements
• No clinically relevant findings in medical history or on physical examination
• Screening IGRA negative
• Willing to be tested for evidence of SARS-CoV-2 infection and to allow public health notification of the results

You may not qualify if:

• Any clinically significant respiratory disease, including asthma
• Current smoker (defined as any smoking including e-cigarettes in the last 3 months)
• History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, any essential study procedure, sedative drugs, or any local or general anaesthetic agents
• Clinically significant history of skin disorder, allergy, atopy, cancer (except BCC of the skin or CIS of the cervix), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
• Any autoimmune conditions or immunodeficiency (including HIV)
• Previous diagnosis or treatment for TB disease or latent TB infections
• Clinical, radiological, or laboratory evidence of current active TB disease or latent TB infection
• Previous receipt of any investigational TB vaccine
• Positive HBsAg, HCV or HIV antibodies
• Concurrent use of oral, inhaled or systemic steroid medication or use for more than 14 days within the last 6 months (steroids used as a cream or ointment are permissible), or the use of other immunosuppressive agents concurrently or for more than 14 days within the last 6 months
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned study challenge date
• Current use of any medication or other drug taken through the nasal or inhaled route including cocaine or other recreational drugs
• Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
• Pregnancy, lactation or intention to become pregnant during study period
• Previously resident for more than 12 months concurrently in a tropical climate where significant non-tuberculous mycobacterial exposure is likely

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX37LE, United Kingdom

Location

Related Publications (1)

• Fredsgaard-Jones T, Harris SA, Morrison H, Ateere A, Nassanga B, Ramon RL, Mitton C, Fletcher E, Decker J, Preston-Jones H, Jackson S, Mawer A, Satti I, Barer M, Hinks T, Bettinson H, McShane H. A dose escalation study to evaluate the safety of an aerosol BCG infection in previously BCG-vaccinated healthy human UK adults. Front Immunol. 2024 Nov 14;15:1427371. doi: 10.3389/fimmu.2024.1427371. eCollection 2024.

  PMID: 39611145 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Professor Helen McShane
• Organization: University of Oxford

helen.mcshane@ndm.ox.ac.uk

01865 617606

Study Officials

• Helen McShane, Professor

  University of Oxford

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I dose-escalation clinical challenge study in historically BCG-vaccinated healthy adult volunteers in which BCG will be administered via the aerosol inhaled route. There will be four study groups with three volunteers in each group. Volunteers will be sequentially enrolled into each group in turn based on their availability. The first volunteer in each group will be challenged at least 1 hour apart from any subsequent volunteers. There will be a review of safety data at least 7 days after challenge of all volunteers within each dose group. This safety review will be performed by the Safety Monitoring Committee (SMC). Dose escalation into the next group will only occur if there are no safety concerns. Safety review will include assessment of symptom diary card, safety bloods and lung function results.

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: March 2, 2021
• Study Start: May 17, 2022
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: February 6, 2025
• Results First Posted: February 6, 2025

Record last verified: 2025-01

Locations

GB (1)