Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01194180
First received: August 31, 2010
Last updated: August 29, 2012
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Culture and RT-PCR quantification of BCG in challenge site biopsy [ Time Frame: 10 weeks post biopsy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Established and exploratory markers of cell mediated immunity in blood samples and biopsied tissue [ Time Frame: 10 weeks post biopsy ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: May 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
BCG-naive subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
BCG vaccination at day C (challenge day) then punch biopsy at day C+14
Experimental: Group B
BCG-naïve subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14
Experimental: Group C
BCG-experienced subjects receiving intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: BCG: 100 microlitres ~ 2-8 x 105 pfu
BCG vaccination at day C (challenge day) then punch biopsy at day C+14
Experimental: Group D
BCG-experienced subjects receiving intradermal injection of MVA85A followed by intradermal "challenge" injection of BCG and challenge site punch biopsy
Biological: MVA85A: 1 x 108 pfu BCG: 100 microlitres ~ 2-8 x 105 pfu
MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • 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)

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194180

Locations
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxon, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Helen McShane University of Oxford
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01194180     History of Changes
Other Study ID Numbers: TB023
Study First Received: August 31, 2010
Last Updated: August 29, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
Mycobacterium tuberculosis
BCG
MVA85A

Additional relevant MeSH terms:
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014