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Safety and Immunogenicity of MVA85A, in Healthy Volunteers in Cape Town

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 1

Locations

South Africa

Study Type

Interventional

Intervention

MVA 85A

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, TB, MVA 85A

Eligibility Criteria

12 Years - 50 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy adults aged 18 to 50 years (for the first 2 arms)
Healthy adolescents (aged 12-14) for the third arm of the study
Screening Elispot negative (less than 17 spots/million PBMC) in all 3 ESAT6 pools and all 3 CFP10 pools
Mantoux test <15mm (<10mm if BCG naïve)
CXR normal with no evidence of active or past TB
For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination
Agreement to refrain from blood donation during the course of the study
Written informed consent
Willingness to undergo an HIV test

Exclusion Criteria:

Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix I
Mantoux >15mm
Prior receipt of a recombinant MVA or Fowlpox vaccine
Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisolone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
Evidence of cardiovascular disease
History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
History of diabetes mellitus
Chronic or active neurological disease requiring ongoing specialist or medical supervision
Chronic gastrointestinal disease requiring ongoing specialist or medical supervision
History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
Seropositive for hepatitis B surface antigen (HBsAg)
Seropositive for hepatitis C virus (antibodies to HCV)
Evidence of serious psychiatric condition
Any other on-going chronic illness requiring hospital specialist or medical supervision
Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
Pregnant or lactating female
Female who is willing or intends to become pregnant during the study
Any history of anaphylaxis in reaction to vaccination
Inability to give informed consent
PI assessment of lack of willingness to participate and comply with all requirements of the protocol
Any other finding which in the opinion of the investigator would significantly increase the risk of having an adverse outcome from participating in this protocol

Sites / Locations

University Cape Town

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm Description

12 adults with prior BCG

12 adults without prior BCG

12 Adolescents

Outcomes

Primary Outcome Measures

To assess the safety of a single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects. The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events (AEs).

Secondary Outcome Measures

To assess the immunogenicity of a single vaccination with MVA85A in healthy subjects. The specific endpoints for immunogenicity will be markers of cell-mediated immunity as outlined above

Full Information

NCT ID

NCT00460590

First Posted

April 13, 2007

Last Updated

August 6, 2008

Sponsor

University of Oxford

Collaborators

University of Cape Town

1. Study Identification

Unique Protocol Identification Number

NCT00460590

Brief Title

Safety and Immunogenicity of MVA85A, in Healthy Volunteers in Cape Town

Official Title

A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine MVA85A, in Healthy Volunteers With no Evidence of Infection With Mycobacterium Tuberculosis, in Cape Town

Study Type

Interventional

2. Study Status

Record Verification Date

June 2008

Overall Recruitment Status

Completed

Study Start Date

October 2005 (undefined)

Primary Completion Date

June 2008 (Actual)

Study Completion Date

June 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University of Oxford

Collaborators

University of Cape Town

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is designed to evaluate the safety of MVA85A in healthy volunteers in Cape Town. We have shown that MVA85A is safe and immunogenic in both a mycobacterially naïve population in the UK and in a more mycobacterially exposed population in The Gambia. The studies described here will be to assess the safety of MVA85A in 2 groups of adults, those with and without prior BCG vaccination. Once safety data has been obtained in these 2 groups, we will assess the safety of MVA85A in adolescents who have been previously vaccinated with BCG.

Detailed Description

This is an open label Phase I safety study of a single intradermal injection of 5 x 107pfu MVA85A, when administered to healthy subjects with no evidence of infection with M.tb Sample size: This is an observational and descriptive safety study, 12 subjects with evidence of prior BCG vaccination and 12 adults with no evidence of prior BCG vaccination will be recruited and vaccinated with MVA85A. This sample size should allow determination of the magnitude of the outcome measures, especially of serious and severe adverse events rather than aiming to obtain statistical significance. Once three month follow-up of these two arms of the study is complete, we will recruit 12 adolescent school children (aged 12-14) and assess the safety and immunogenicity of a single immunisation with MVA85A in this group. Rules for progression from adult studies to adolescents: No increased incidence in local and systemic side-effects compared with trials with MVA85A in Oxford and The Gambia. In the trials in the UK and The Gambia, all volunteers experience some mild local side-effects for 1-4 days after vaccination. Approximately two- thirds of volunteers experience some mild systemic side-effects in the first 24 hours after vaccination. These are self-limiting and all spontaneously resolve. These side-effects are consistent with data from use with other recombinant MVAs expressing other antigens (Moorthy VS et al, 2003). Immune responses measured 1 week after vaccination. We see strong immune responses 1 week after vaccination in the Oxford and Gambian volunteers (McShane et al, 2004). We do not know how long the responses in the South African volunteers will last for, but we would expect to see the induction of significant (compared with baseline) immune responses as measured by the ex-vivo Elispot assay, 1 week after vaccination

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis, TB, MVA 85A

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

12 adults with prior BCG

Arm Title

Arm Type

Experimental

Arm Description

12 adults without prior BCG

Arm Title

Arm Type

Experimental

Arm Description

12 Adolescents

Intervention Type

Biological

Intervention Name(s)

MVA 85A

Intervention Description

ID vaccine

Primary Outcome Measure Information:

Title

Time Frame

year

Secondary Outcome Measure Information:

Title

To assess the immunogenicity of a single vaccination with MVA85A in healthy subjects. The specific endpoints for immunogenicity will be markers of cell-mediated immunity as outlined above

Time Frame

year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy adults aged 18 to 50 years (for the first 2 arms) Healthy adolescents (aged 12-14) for the third arm of the study Screening Elispot negative (less than 17 spots/million PBMC) in all 3 ESAT6 pools and all 3 CFP10 pools Mantoux test <15mm (<10mm if BCG naïve) CXR normal with no evidence of active or past TB For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination Agreement to refrain from blood donation during the course of the study Written informed consent Willingness to undergo an HIV test Exclusion Criteria: Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis as defined in Appendix I Mantoux >15mm Prior receipt of a recombinant MVA or Fowlpox vaccine Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisolone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products Evidence of cardiovascular disease History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) History of diabetes mellitus Chronic or active neurological disease requiring ongoing specialist or medical supervision Chronic gastrointestinal disease requiring ongoing specialist or medical supervision History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis) Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week Seropositive for hepatitis B surface antigen (HBsAg) Seropositive for hepatitis C virus (antibodies to HCV) Evidence of serious psychiatric condition Any other on-going chronic illness requiring hospital specialist or medical supervision Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate Pregnant or lactating female Female who is willing or intends to become pregnant during the study Any history of anaphylaxis in reaction to vaccination Inability to give informed consent PI assessment of lack of willingness to participate and comply with all requirements of the protocol Any other finding which in the opinion of the investigator would significantly increase the risk of having an adverse outcome from participating in this protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Greg Hussey, Professor

Organizational Affiliation

University Cape Town

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Cape Town

City

Cape Town

ZIP/Postal Code

7925

Country

South Africa

12. IPD Sharing Statement

Citations:

PubMed Identifier

25466778

Citation

Tanner R, Kakalacheva K, Miller E, Pathan AA, Chalk R, Sander CR, Scriba T, Tameris M, Hawkridge T, Mahomed H, Hussey G, Hanekom W, Checkley A, McShane H, Fletcher HA. Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. BMC Infect Dis. 2014 Dec 3;14:660. doi: 10.1186/s12879-014-0660-7.

Results Reference

derived

PubMed Identifier

18582195

Citation

Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, Lang T, Veldsman A, Hatherill M, Merwe Lv, Fletcher HA, Mahomed H, Hill AV, Hanekom WA, Hussey GD, McShane H. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis. 2008 Aug 15;198(4):544-52. doi: 10.1086/590185. Erratum In: J Infect Dis. 2011 Jul;204(1):176.

Results Reference

derived

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Safety and Immunogenicity of MVA85A, in Healthy Volunteers in Cape Town

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