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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06148025




Registration number
NCT06148025
Ethics application status
Date submitted
29/09/2023
Date registered
28/11/2023

Titles & IDs
Public title
Antibiotics and Vaccine Immune Responses Study
Scientific title
A Human Experimental Medicine Study to Assess Whether the Gut Microbiota Regulates Specific and Non-specific Immune Responses to Vaccination
Secondary ID [1] 0 0
2023/HREC00066
Universal Trial Number (UTN)
Trial acronym
AVIRS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vaccine Response Impaired 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - BCG vaccine
Treatment: Other - Yellow Fever vaccine
Treatment: Drugs - Vancomycin Oral Capsule
Treatment: Drugs - Neomycin Oral Product

Experimental: Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine - Randomised to receive antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later

Experimental: Substudy 1 - BCG vaccine, no antibiotics and 2nd BCG vaccine - Randomised to receive no antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later

Experimental: Substudy 1 - BCG vaccine, antibiotics and placebo vaccine - Randomised to receive antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later

Experimental: Substudy 1 - BCG vaccine, no antibiotics and placebo vaccine - Randomised to receive no antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later

Experimental: Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine - Randomised to receive antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later

Experimental: Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine - Randomised to receive no antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later

Experimental: Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine - Randomised to receive antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later

Experimental: Substudy 2 - Yellow Fever vaccine, no antibiotics and placebo vaccine - Randomised to receive no antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later


Treatment: Other: BCG vaccine
0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

Treatment: Other: Yellow Fever vaccine
0.5ml injected subcutaneously

Treatment: Drugs: Vancomycin Oral Capsule
500mg every 6 hours for 3 days

Treatment: Drugs: Neomycin Oral Product
1000mg every 6 hours for 3 days
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sub-study 1 BCG re-challenge
Timepoint [1] 0 0
5 years
Primary outcome [2] 0 0
Sub-study 2 Yellow Fever vaccine
Timepoint [2] 0 0
5 years
Secondary outcome [1] 0 0
Sub-study 1 - Bacterial load
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Sub-study 2 - Bacterial load
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Sub-study 1 - Microbiota diversity
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Sub-study 2 - Microbiota diversity
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Sub-study 1 - Mycobacterial load
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Sub-study 1 - Mycobacterial IFN? responses
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Sub-study 1 - Mycobacterial T cell activation marker responses
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
Sub-study 2 - Peak viraemia
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Sub-study 2 - Heterologous TNFa responses following R848 stimulation
Timepoint [9] 0 0
5 years
Secondary outcome [10] 0 0
Sub-study 2 - Heterologous TNFa responses following LPS stimulation
Timepoint [10] 0 0
5 years
Secondary outcome [11] 0 0
Sub-study 2 - Heterologous TNFa responses following fungal stimulation
Timepoint [11] 0 0
5 years

Eligibility
Key inclusion criteria
* 18-35 years old
* Provided a signed and dated informed consent form
* BCG naïve (Arm 1) and BCG and YF vaccine naïve (Arm 2)
* Willing to take short antibiotic course
* Willing to undergo a punch biopsy (Arm 1)
* Willing to have up to 7 blood samples and 3 stool samples collected over 5-7 months
* Not pregnant or intending to get pregnant for the duration of the study (a pregnancy test will be offered to females)
Minimum age
18 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Previous BCG or YF vaccination
* Previous YF infection
* Evidence of latent TB infection (LTBI) (assessed through a questionnaire) (IGRA to confirm if needed)
* People with contraindications for BCG vaccination:

* malignancies involving bone marrow or lymphoid systems, primary or secondary immunodeficiencies, HIV infection
* moderate/severe skin disease including eczema, dermatitis or psoriasis
* requiring immunosuppressive drugs or other immune modifying drugs e.g. corticosteroids, non-biological immunosuppressants, biological agents (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha)
* People with contraindications to YF vaccination:

* History of thymus disease, including myasthenia gravis, thymoma, thymectomy, DiGeorge syndrome, thymic damage from chemoradiotherapy or graft-versus-host disease
* YF vaccination is contraindicated in immunocompromised individuals, including individuals who have HIV infection, primary immunodeficiencies (including inherited IFNAR1 deficiency), or are taking corticosteroids or other immunosuppressive agents and haematopoietic stem cell transplant recipients
* People who have had a haematopoietic stem cell transplant
* Individuals with history of severe allergic reactions to egg or chicken proteins
* Pregnant or breastfeeding or planning to become pregnant
* History of renal disease/insufficiency
* Tattoo obscuring BCG vaccination site(s)
* Any history of severe allergic reaction or anaphylaxis to vaccination
* People with chronic serious underlying illness
* Have received any prescribed oral or intravenous antibiotic in the 28 days prior to study visits 1 and 4 (including isoniazid, rifampicin, streptomycin and ethambutol as these particular antibiotics have activity against M. bovis)

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2028
Actual
Sample size
Target
348
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
South Australian Health and Medical Research Institute - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
South Australian Health and Medical Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Adelaide Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Flinders University
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Sydney
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Telethon Kids Institute
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Centenary Institute of Cancer Medicine and Cell Biology
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Simone Barry
Address 0 0
Royal Adelaide Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Lynn
Address 0 0
Country 0 0
Phone 0 0
+61 8 8128 4053
Fax 0 0
Email 0 0
david.lynn@sahmri.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Non-identifiable individual participant data from the study may be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept SAHMRI's conditions, under a collaborator agreement, for accessing:

* Individual participant data that underlie the results reported in our articles after deidentification (text, tables, figures and appendices)
* Study protocol, Statistical Analysis Plan, PICF

Molecular data generated from this study (i.e. transcriptomic, epigenomic and metagenomic) will be labelled with a unique identification code and stored on an appropriate data repository (e.g. Gene Expression Omnibus, Sequence Read Archive) with demographic information (age and sex). No identifying participant information will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
When will data be available (start and end dates)?
At time of publication. Data will be available indefinitely.
Available to whom?
Researchers from a recognised research institution can approach SAHMRI for access of data. The researcher will need to provide evidence that the proposed use of the data has been ethically reviewed and approved by an Institutional Review Board (IRB)/ Human Research Ethics Committee(HREC), and accept SAHMRI's conditions, under a collaborator agreement.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06148025