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TuberculosisPhase 1NCT01194180

A BCG Challenge Model Study to Assess Anti-mycobacterial Immunity Induced by BCG and a Candidate TB Vaccine, MVA85A

A Phase 1 study testing BCG: 100 microlitres ~ 2-8 x 105 pfu and MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu in people with Tuberculosis, run by University of Oxford at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the BCG 'challenge' model a four-arm study design has been chosen. Twelve subjects will be recruited into each arm of the study. Allocation of BCG-naïve volunteers to either group A or B, and BCG-vaccinated volunteers to either group C or D, will be performed on a one-to-one… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Tuberculosis
What is being tested?
BCG: 100 microlitres ~ 2-8 x 105 pfu and MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited Kingdom
Study dates
May 2010to Jan 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy adult aged 18-55 years
  • Resident in or near Oxford for the duration of the study period
  • No relevant findings in medical history or on physical examination
  • Willingness to allow the Investigators to discuss the individual's medical history with their GP
  • Willingness to use effective contraception for the duration of the study period (females only)
  • Agreement to refrain from blood donation during the course of the study
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  • Willingness to give written informed consent
  • Agreement to allow the Investigator to register volunteer details with a confidential database to prevent concurrent entry into clinical trials
  • Able and willing (in the Investigator's opinion) to comply with all the study requirements
  • Additional criteria to be met for subjects in group A:
  • None
  • Additional criteria to be met for subjects in group B:
  • Willingness to use continuous effective barrier contraception for three months after receiving
  • MVA85A vaccination (males and females)
  • Additional criteria to be met for subjects in group C:
  • Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation)
  • Additional criteria to be met for subjects in group D:
  • Confirmation of prior vaccination with BCG not less than three months prior to projected study enrolment date (by visible BCG scar on examination or written documentation)
  • Willingness to use continuous effective barrier contraception for three months after receiving MVA85A vaccination (males and females)

Who cannot join

  • Clinical, radiological, or laboratory evidence of current active TB disease
  • Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT test (>17 sfc/million PBMC) in any ESAT6 peptide or CFP10 peptide poola
  • Previous vaccination with candidate TB vaccine MVA85A or candidate TB vaccine FP85A
  • Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
  • History of serious psychiatric condition
  • Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
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  • History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study vaccine
  • Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the studyb
  • Positive HBsAg, HCV or HIV antibodies
  • Female currently lactating, confirmed pregnancy or intention to become pregnant during study period
  • Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 60 days prior to dosing with the study vaccine, or planned use during the study period
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
  • Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk or may influence the result of the study or may affect the volunteer's ability to participate in the study
  • Additional exclusion criteria for subjects in group A:
  • Previous vaccination with BCG
  • Additional exclusion criteria for subjects in group B:
  • Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A
  • Previous vaccination with BCG
  • Additional exclusion criteria for subjects in group C:
  • None
  • Additional exclusion criteria for subjects in group D:
  • Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Centre for Clinical Vaccinology and Tropical Medicine

    Oxford, Oxon, OX3 7LJ

Other trials in United Kingdom

About this study

Official title: A Phase 1 Study to Evaluate a BCG Challenge Model as a Method of Assessing Anti-mycobacterial Immunity Induced by BCG and a Candidate TB Vaccine, MVA85A, Alone and in Combination

The purpose of this study is to evaluate the BCG 'challenge' model a four-arm study design has been chosen. Twelve subjects will be recruited into each arm of the study. Allocation of BCG-naïve volunteers to either group A or B, and BCG-vaccinated volunteers to either group C or D, will be performed on a one-to-one alternating basis. Subjects in each group will be challenged by BCG administered intradermally. Prior to challenge, pre-existing immunity to TB will be induced by vaccination with BCG, MVA85A, and both in combination (when compared to BCG- \& MVA85A-naïve individuals). BCG quantification will be assessed by analysing the tissue obtained in a punch biopsy of volunteers' skin over the site of BCG 'challenge' vaccination. Any reduction in BCG quantification between groups will then be correlated to existing (and future) laboratory assays of vaccine-induced immune responses in order to identify potential immunological correlates of protection.

Conditions
Tuberculosis
Being tested
BCG: 100 microlitres ~ 2-8 x 105 pfu, MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
Keywords
Mycobacterium tuberculosis, BCG, MVA85A
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BCG: 100 microlitres ~ 2-8 x 105 pfuBiological

    BCG vaccination at day C (challenge day) then punch biopsy at day C+14

  • MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfuBiological

    MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14

Study groups in NCT01194180
Study groupRoleWhat they receive
Group AExperimentalBCG-naive subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy
Receives: Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
Group BExperimentalBCG-naïve subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy
Receives: Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
Group CExperimentalBCG-experienced subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy
Receives: Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
Group DExperimentalBCG-experienced subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy
Receives: Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Culture and RT-PCR quantification of BCG in challenge site biopsy

    Measured: 10 weeks post biopsy

Secondary outcomes (1)
  1. Established and exploratory markers of cell mediated immunity in blood samples and biopsied tissue

    Measured: 10 weeks post biopsy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Sep 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionJan 2012
  4. Study completionJan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01194180
Sponsor's protocol ID
TB023
Status last verified
Oct 2011
First submitted
31 Aug 2010
Last updated
30 Aug 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Tanner R, Satti I, Harris SA, O'Shea MK, Cizmeci D, O'Connor D, Chomka A, Matsumiya M, Wittenberg R, Minassian AM, Meyer J, Fletcher HA, McShane H. Tools for Assessing the Protective Efficacy of TB Vaccines in Humans: in vitro Mycobacterial Growth Inhibition Predicts Outcome of in vivo Mycobacterial Infection. Front Immunol. 2020 Jan 10;10:2983. doi: 10.3389/fimmu.2019.02983. eCollection 2019.

    PubMed 31998295
  • 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.

    PubMed 24273174

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BCG: 100 microlitres ~ 2-8 x 105 pfu and MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu in people with Tuberculosis, run by University of Oxford at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Culture and RT-PCR quantification of BCG in challenge site biopsy (time frame: 10 weeks post biopsy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01194180, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2012.

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