A Phase I Study of a New Tuberculosis (TB) Vaccine, MVA85A, in Healthy Volunteers With HIV

NCT ID: NCT00731471

Last Updated: 2011-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2011-01-31

Brief Summary

This is an open Phase I study of a candidate TB vaccine, MVA85A, in healthy subjects who are infected with HIV. It is designed to study the safety and immunogenicity of the vaccine.

Detailed Description

This study is designed to evaluate the safety of MVA85A in healthy volunteers in Senegal who are infected with HIV. In phase I studies, a single vaccination with MVA85A, when administered at a dose of 5 x 107pfu intradermally, has been shown to be safe in both mycobacterially naïve individuals, those previously vaccinated with BCG and latently infected individuals. We will use 1 x 10^8 pfu MVA85A intradermally in this study. A trial in BCG vaccinated subjects showed that the higher dose (1 x 10^8 pfu MVA85A) induced a significantly higher immune response but did not have a higher AE profile. In addition, because of a variable immune response, the trial in HIV positive subjects in the UK is split into two groups, the first getting 5 x 10^7 pfu and the second getting 1 x 10^8 pfu MVA85A. It has, therefore, been decided to use the higher dose in order to maximise the immune response whilst maintaining a good safety profile.

Conditions

Tuberculosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

12 Healthy adults infected with HIV

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

Modified vaccinia virus Ankara expressing antigen 85A from Mycobacterium tuberculosis. Both arms will receive two vaccinations six months apart.

2

12 HIV+ adults on antiretroviral therapy

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

Modified vaccinia virus Ankara expressing antigen 85A from Mycobacterium tuberculosis. Both arms will receive two vaccinations six months apart.

Interventions

MVA85A

Modified vaccinia virus Ankara expressing antigen 85A from Mycobacterium tuberculosis. Both arms will receive two vaccinations six months apart.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Healthy adults aged 18 to 50 years
• Resident in or near Dakar for the duration of the study
• Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's HIV lead physician
• Willing to use effective contraception throughout duration of study (if female)
• HIV antibody positive; diagnosed at least 6 months previously
• CD4 count >300
• Arm 1: HIV viral load not >100,000 copies per millilitre
• Arm 2: Undetectable HIV viral load
• Written informed consent

Exclusion Criteria

• Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or on urinalysis
• Group 1 only: Any ARV therapy within the past 6 months
• Previous history of TB disease and/or treatment
• Any AIDS defining illness
• Group 1: CD4 count nadir <300
• Group 2: CD4 count nadir <100
• CXR showing TB or evidence of other active infection
• 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.)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
• Presence of any underlying disease that compromises the diagnosis and evaluation of response to the vaccine (including evidence of cardiovascular disease, history of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ), history of insulin requiring diabetes mellitus, any ongoing chronic illness requiring ongoing specialist supervision (e.g., gastrointestinal), and chronic or active neurological disease)
• History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
• Suspected or known current drug and/or alcohol abuse
• Seropositive for hepatitis B surface antigen (HBsAg) and/ or hepatitis C (antibodies to HCV)
• Evidence of serious psychiatric condition
• Any other on-going chronic illness requiring hospital specialist supervision
• Any confirmed or suspected immunosuppressive or immunodeficient condition, other than HIV infection, such as asplenia
• Evidence of hepatomegaly
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Pregnant/lactating female and any female who is willing or intends to become pregnant during the study
• Any history of anaphylaxis in reaction to vaccination
• PI assessment of lack of willingness to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the participant's risk of suffering an adverse outcome

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Le Dantec, Dakar, Senegal

UNKNOWN

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

University of Oxford

Principal Investigators

Helen McShane

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Souleymane Mboup

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Le Dantec

Locations

Centre Hospitalier Le Dantec

Dakar, , Senegal

Countries

Senegal

References

Dieye TN, Ndiaye BP, Dieng AB, Fall M, Brittain N, Vermaak S, Camara M, Diop-Ndiaye H, Ngom-Gueye NF, Diaw PA, Toure-Kane C, Sow PS, Mboup S, McShane H. Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naive subjects gives comparable immunogenicity to one dose in ART+ subjects. PLoS One. 2013 Jun 28;8(6):e67177. doi: 10.1371/journal.pone.0067177. Print 2013.

Reference Type: DERIVED

PMID: 23840618 (View on PubMed)

Other Identifiers

TB019

Identifier Type: -

Identifier Source: org_study_id