A Phase I Study of the Safety and Immunogenicity of a Recombinant MVA Vaccine Encoding a Secreted Antigen From M. Tuberculosis, Antigen 85A, Delivered Intradermally by a Needle Injection in Healthy Volunteers Who Have Received BCG Immunisation 1 Month Previously

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT00427453

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase I study to test the immunogenicity of a recombinant vaccine based on Modified Vaccinia Ankara (MVA) expressing the antigen 85A (from Mycobacterium tuberculosis). This vaccine is delivered intradermally by a needle injection in healthy volunteers previously vaccinated with BCG.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: MVA85A	Phase 1

Detailed Description

Selection of volunteers

Volunteers for the study will be recruited through advertisements. Each volunteer will have received an information sheet concerning the study and will have agreed to participate in writing. Volunteers will be given at least 48 hours between reading the information leaflet and agreeing to participate. Female volunteers will be told of the theoretical risk of congenital anomaly should they become pregnant during the study and only those who undertake to take precautions to avoid pregnancy during the study period will be eligible. Volunteers will give signed consent for their GP's to be notified about their participation in the trial. The GP will be faxed a letter on the day of screening and asked to reply if they know of a reason why the volunteer should not take part. The signed consent form will also be faxed with the letter.

Screening

Volunteers will be asked to sign the informed consent form for screening. The following will be performed:

Medical history and examination
Laboratory evaluations - including clinical chemistry, haematology, HLA typing, anti-vaccinia antibodies, anti-HBV antibodies, anti-HCV antibodies, anti-HIV antibodies
Heaf test - to exclude prior exposure to TB
Urinalysis and urine pregnancy test if female

Inclusion Criteria

Healthy adult aged 18-55 years.
Normal medical history and physical examination.
Normal urine dipstick, blood count, liver enzymes, and creatinine.

Exclusion Criteria
Exposure to TB/BCG vaccination at any point. Previous residence in a TB endemic area.
Clinically significant history of skin disorder (eczema, psoriasis, etc.), allergy, immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness, psychiatric disorder, drug or alcohol abuse.
Oral or systemic steroid medication or the use of immunosuppressive agents.
Positive HIV antibody test, HCV antibody test or positive HBV serology except post-vaccination.
Heaf test greater than Grade 0
Confirmed pregnancy
Previous MVA immunisations
Withdrawal Criteria
Withdrawal of consent by subject for any reason
Loss to follow-up
Non-compliance with study procedures
Protocol violation
Serious adverse event (as defined in Appendix 3)
Any other reason at discretion of the Principal Investigator
Confirmed pregnancy during study period
Immunisation

On Day 0, subjects will receive a single intradermal injection of 0.1ml BCG (SSI strain) over the deltoid muscle. Blood will be taken at 2 weeks and 4 weeks after this immunisation. At 4 weeks, after blood has been taken, volunteers will be immunised with 5 x 107pfu MVA85A in 0.1ml. Subjects will be observed for an hour after MVA85A immunisation. Vital signs will be monitored at 30 and 60 minutes post-immunisation. Local reactions at the site of administration will be evaluated at 60 minutes.

A photograph of the injection site may be taken at 48 hours (with written consent). The injection site will be reviewed 7 days after each immunization.

Blood will be taken at the following time points: At the screening visit*, prior to the BCG vaccination, 2 weeks and 4 weeks after BCG, *1 week after the MVA85A vaccination, 2 weeks, 4 weeks, *8 weeks, and *24 weeks after the vaccination. Up to 55 mls will be taken at any one time with the total being no more than 500 mls over the study period. *Samples taken on these dates will be tested for full blood count and biochemical screen. Immunological assays will be performed at all time points to determine vaccine immunogenicity. A pregnancy test will be performed prior to vaccination for female volunteers. Peripheral blood mononuclear cells will be prepared for cellular immunological assays to be performed without or following cryopreservation. Other serological measures of immune response, i.e. antibody titres, will be assayed on frozen plasma samples.

All blood tests will be taken within 1-3 days of the due date as described in the schedule above.

Endpoints

The occurance and severity of local side-effects The occurance and severity of systemic side-effects The induction of T cell responses (as measured by an interferon-gamma Elispot assay).

Proliferation assays and cytotoxic T cell assays will be performed on strong CD4+ and CD8+ responses respectively.

Study Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase I Study of the Safety and Immunogenicity of a Recombinant MVA Vaccine Encoding a Secreted Antigen From M. Tuberculosis, Antigen 85A, Delivered Intradermally by a Needle Injection in Healthy Volunteers Who Have Received BCG Immunisation 1 Month Previously

Study Start Date :

Jun 1, 2003

Study Completion Date :

Mar 1, 2005

Outcome Measures

Primary Outcome Measures

The occurance and severity of local and systemic side effects will be monitored. Vital signs and local reactions will be monitored at 30 and 60 minutes after each mmunisation (and after 7 days). []
Blood will be taken at: the screening visit, prior to the BCG vaccination, 1 and 4 weeks after the BCG vaccination, and also at 1,4, 8, 12 and 24 weeks after the MVA85A vaccination. []

Secondary Outcome Measures

Immunogenicity will be measured: The induction of T cell responses (as measured by an interferon-gamma Elispot assay) will be performed on PBMCs from blood samples taken at the specified time points. []
Proliferation assays and cytotoxic T cell assays will be performed. Other serological measures of immune response, i.e. antibody titres will be analysed on frozen plasma samples. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy adult aged 18-55 years.
Normal medical history and physical examination.
Normal urine dipstick, blood count, liver enzymes, and creatinine.

Exclusion Criteria:

Exposure to TB/BCG vaccination at any point. Previous residence in a TB endemic area.
Clinically significant history of skin disorder (eczema, psoriasis, etc.), allergy, immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness, psychiatric disorder, drug or alcohol abuse.
Oral or systemic steroid medication or the use of immunosuppressive agents.
Positive HIV antibody test, HCV antibody test or positive HBV serology except post-vaccination.
Heaf test greater than Grade 0
Confirmed pregnancy
Previous MVA immunisations