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

Tuberculosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01194180
• Other study ID #: TB023
• Status: Completed
• Phase: Phase 1
• First received: August 31, 2010
• Last updated: August 29, 2012
• Start date: May 2010
• Est. completion date: January 2012

Study information

• Verified date: October 2011
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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:

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:

Additional exclusion criteria for subjects in group D:

• Previous vaccination with a recombinant MVA vaccine other than MVA85A or FP85A

Study Design

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

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Biological:
• BCG: 100 microlitres ~ 2-8 x 105 pfu
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 pfu
MVA85A vaccination at day C-28 followed by BCG vaccination at day C (challenge day) then biopsy at day C+14

Locations

Country	Name	City	State
United Kingdom	Centre for Clinical Vaccinology and Tropical Medicine	Oxford	Oxon

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Culture and RT-PCR quantification of BCG in challenge site biopsy		10 weeks post biopsy	No
Secondary	Established and exploratory markers of cell mediated immunity in blood samples and biopsied tissue		10 weeks post biopsy	No