Tuberculosis Clinical Trial
Official title:
A Human Challenge Study to Evaluate Innate and Adaptive Immune Responses to a Controlled Human Infection With BCG Administered by the Intradermal or Aerosol Inhaled Route in Healthy, BCG-naïve or Historically BCG-vaccinated, UK Adult Volunteers
Verified date | January 2024 |
Source | University of Oxford |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
TB043 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive (Group 1-7) as well as historically BCG vaccinated UK adults (Group 8) . The trial will also look to evaluate and compare the amount of BCG recovered from the lungs as various points after challenge.
Status | Active, not recruiting |
Enrollment | 94 |
Est. completion date | June 2024 |
Est. primary completion date | June 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 50 Years |
Eligibility | Inclusion Criteria: - Healthy adult aged 18-50 years - Resident in or near Oxford for the duration of the study period - Screening IGRA negative - No relevant findings in medical history or on physical examination - Allow the Investigators to discuss the individual's medical history with their GP - Use effective contraception (see below) for the duration of the study period (people of child bearing potential only) - Refrain from blood donation during the study - Give written informed consent - Allow the Investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials - Willing to be tested for evidence of SARS-CoV-2 infection, if indicated and to allow public health notification of results if required. - Able and willing (in the Investigator's opinion) to comply with all the study requirements - For Group 8 only- previously vaccinated with BCG (at least 12 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records) Exclusion Criteria: - Previously resident for more than 12 months concurrently in a rural area of a tropical climate where significant non-tuberculous mycobacterial exposure is likely - Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period - Prior vaccination with BCG (G1-7 only) or any other candidate TB vaccine (all groups). - Administration of immunoglobulins and/or any blood products within the three months preceding the planned study challenge date - Clinically significant history of skin disorder, allergy, atopy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse - Concurrent oral, inhaled or systemic steroid medication or the concurrent use of other immunosuppressive agents - Shares a household with someone with clinically significant immunodeficiency (either from infection or medication) who is deemed to be at risk of developing disseminated BCG infection if exposed to BCG - History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, essential study procedures, sedative drugs, or any local or general anaesthetic agents - Pregnancy, lactation or intention to become pregnant during study period - Any clinically significant respiratory disease, including asthma - Current smoker (defined as any smoking including e-cigarettes in the last 3 months) - Clinically significant abnormality on screening chest radiograph - Clinically significant abnormality of pulmonary function - Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy - Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs - Clinical, radiological, or laboratory evidence of current active TB disease - Past treatment for TB disease - Any clinically significant abnormality of screening blood or urine tests - Positive HBsAg, HCV or HIV antibodies - Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the study or impair interpretation of the study data People of Child Bearing Potential (POCBP) are required to use an effective form of contraception during the course of the study. Acceptable forms of contraception for POCBP volunteers include: - Established use of oral, injected on implanted hormonal methods of contraception - Placement of an intrauterine device (IUD) or intrauterine system (IUS) - Permanent sterilisation or bilateral tubal occlusion - Barrier methods of contraception (condom; or occlusive cap with spermicide) - Male sterilisation, if the vasectomised partner is the sole partner for the subject - True abstinence, when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence and withdrawal are not acceptable methods of contraception) - Exclusive same sex intercourse |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital | Oxford | Oxfordshire |
United Kingdom | Oxford University Hospitals- John Warin Ward, University of Oxford | Oxford | Oxfordshire |
Lead Sponsor | Collaborator |
---|---|
University of Oxford | National Institute for Health Research, United Kingdom, University of Leicester, Wellcome Trust |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Adverse Events (AEs) | Collection of AE data at each visit and via diary card, and laboratory parameters of BCG cfu counts in induced sputum, BAL and matrix from adapted duck bill mask collection | Up to day 168 | |
Primary | Identification of markers of innate immunity-cytokines | Established markers of innate immunity in blood, BAL and biopsy samples will be aggregated to determine overall characterisation of innate response. Specifically, cytokine levels will be measured by ELISpot and ELISA. | Up to day 168 | |
Primary | Identification of markers of innate immunity-antigen presenting cells | Established markers of innate immunity in blood, BAL and biopsy samples will be aggregated to determine overall characterisation of innate response. Specifically, the activity of antigen presenting cells will be measured by flow cytometry | Up to day 168 | |
Primary | Identification of markers of innate immunity-inflammation in tissue | Established markers of innate immunity in blood, BAL and biopsy samples will be aggregated to determine overall characterisation of innate response. Specifically IHC staining will be done to examine changes in tissue samples. | Up to day 168 | |
Primary | Identification of markers of adaptive immunity-antibodies | Established markers of adaptive immunity in blood, BAL and biopsy samples will be aggregated to determine overall characterisation of adaptive response. Specifically, the presence of antibodies will be measured. | Up to day 168 | |
Primary | Identification of markers of adaptive immunity-T cells | Established markers of adaptive immunity in blood, BAL and biopsy samples will be aggregated to determine overall characterisation of adaptive response. Specifically, T-cell activity will be determined by a flow cytometry panel. | Up to day 168 | |
Secondary | Mycobacterial growth inhibition assay | MGIA outcome on PBMCs collected at Day 56; readout in CFUs (colony forming units) | Up to day 56 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05738681 -
Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial
|
Phase 2/Phase 3 | |
Recruiting |
NCT05526885 -
Tuberculosis Diagnostic Trial of CAD4TB Screening Alone Compared to CAD4TB Screening Combined With a CRP Triage Test, Both Followed by Confirmatory Xpert MTB/RIF Ultra in Communities of Lesotho and South Africa
|
N/A | |
Completed |
NCT04369326 -
Community Initiated Preventive Therapy for TB
|
N/A | |
Recruiting |
NCT04568967 -
TB-CAPT EXULTANT - HIV
|
N/A | |
Completed |
NCT02337270 -
Phase 1 Clinical Trial of the Safety and Immunogenicity of an Adenovirus-based TB Vaccine Administered by Aerosol
|
Phase 1 | |
Not yet recruiting |
NCT06253715 -
Shortened Regimen for Drug-susceptible TB in Children
|
Phase 3 | |
Recruiting |
NCT04271397 -
Immunological Biomarkers in Tuberculosis Management
|
N/A | |
Withdrawn |
NCT03639038 -
Tuberculosis Diagnosis by Flow Cytometry
|
||
Completed |
NCT03199313 -
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid
|
Phase 1 | |
Recruiting |
NCT04975178 -
Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa
|
Phase 3 | |
Completed |
NCT04463680 -
Rifampin and the Contraceptive Implant
|
Phase 4 | |
Completed |
NCT03973970 -
Assessing the Ability of the T-SPOT®.TB Test (IQ)
|
||
Recruiting |
NCT04230395 -
Alcohol Reduction Among People With TB and HIV in India
|
N/A | |
Completed |
NCT04874948 -
Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment
|
Phase 1 | |
Active, not recruiting |
NCT02906007 -
Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT05917210 -
Peer-led Implementation of TB-HIV Education and Adherence Counseling in Uganda
|
N/A | |
Not yet recruiting |
NCT05845112 -
Start Taking Action For TB Diagnosis
|
||
Not yet recruiting |
NCT06017843 -
Impact Evaluation of Use of MATCH AI Predictive Modelling for Identification of Hotspots for TB Active Case Finding
|
N/A | |
Active, not recruiting |
NCT02715271 -
Study of TB Lesions Obtained in Therapeutical Surgery
|
||
Completed |
NCT02781909 -
Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis
|
Phase 2 |