Safety and Immunogenicity of MVA85A in Volunteers Latently Infected With TB.

NCT00456183 | Completed Phase 1 DMC

• 1 other identifier: TB007
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the safety of MVA85A in healthy volunteers in the UK who are latently infected with M.tb. A single vaccination with MVA85A, when administeredat a dose of 5 x 107pfu intradermally, is safe in both mycobacterially naïve individuals and those previously vaccinated with BCG. We will use the same vaccination regime in this study. Subjects will be defined as being latently infected if they have a positive elispot response to ESAT6 or CFP10. Subjects will be identified from TB contact clinics.

Conditions

Tuberculosis

Keywords

Tuberculosis; Latent; TB; Vaccine; MVA 85A

Outcome Measures

Primary Outcomes (1)

• Safety of a single intradermal injection of 5 x 107pfu MVA85A

  One year

Secondary Outcomes (7)

• Efficacy

  One year

• latently infected with MVA85A on the immune response, both to antigen 85A (the antigen in

• the vaccine) and to ESAT6/CFP10 antigens (M.tb specific).

• Endpoints:

• The specific endpoints for safety and reactogenicity will be actively and passively collected

Interventions

MVA 85A BIOLOGICAL

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18 to 50 years
• Resident in or near Oxford for the duration of the vaccination study
• Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's GP
• Screening Elispot positive (more than 50 spots/million PBMC) for at least any 1 of the 3 ESAT6 peptide pools or any one of the 3 CFP10 pools ; and screening Elispot positive for PPD.
• Heaf test grade II-IV or positive Mantoux test.
• CXR normal; or abnormal but not clinically significant CXR findings with no evidence of past/present TB infection or disease on the CXR.
• 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

You may not qualify if:

• Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis
• Heaf grade IV
• 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, ε 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 insulin requiring diabetes mellitus
• Chronic or active neurological disease requiring ongoing specialist supervision

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Related Publications (8)

• McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med. 2004 Nov;10(11):1240-4. doi: 10.1038/nm1128. Epub 2004 Oct 24.

  PMID: 15502839 BACKGROUND

• Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV. Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J Immunol. 2003 Aug 1;171(3):1602-9. doi: 10.4049/jimmunol.171.3.1602.

  PMID: 12874255 BACKGROUND

• Bejon P, Peshu N, Gilbert SC, Lowe BS, Molyneux CS, Forsdyke J, Lang T, Hill AV, Marsh K. Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya. Clin Infect Dis. 2006 Apr 15;42(8):1102-10. doi: 10.1086/501459. Epub 2006 Mar 14.

  PMID: 16575727 BACKGROUND

• Huygen K, Content J, Denis O, Montgomery DL, Yawman AM, Deck RR, DeWitt CM, Orme IM, Baldwin S, D'Souza C, Drowart A, Lozes E, Vandenbussche P, Van Vooren JP, Liu MA, Ulmer JB. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996 Aug;2(8):893-8. doi: 10.1038/nm0896-893.

  PMID: 8705859 BACKGROUND

• McShane H, Brookes R, Gilbert SC, Hill AV. Enhanced immunogenicity of CD4(+) t-cell responses and protective efficacy of a DNA-modified vaccinia virus Ankara prime-boost vaccination regimen for murine tuberculosis. Infect Immun. 2001 Feb;69(2):681-6. doi: 10.1128/IAI.69.2.681-686.2001.

  PMID: 11159955 BACKGROUND

• Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994 Mar 2;271(9):698-702.

  PMID: 8309034 BACKGROUND

• 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.

  PMID: 25466778 DERIVED

• Sander CR, Pathan AA, Beveridge NE, Poulton I, Minassian A, Alder N, Van Wijgerden J, Hill AV, Gleeson FV, Davies RJ, Pasvol G, McShane H. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium tuberculosis-infected individuals. Am J Respir Crit Care Med. 2009 Apr 15;179(8):724-33. doi: 10.1164/rccm.200809-1486OC. Epub 2009 Jan 16.

  PMID: 19151191 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

MVA 85A

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Helen McShane

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 3, 2007
• First Posted: April 4, 2007
• Study Start: August 1, 2005
• Study Completion: April 1, 2007
• Last Updated: May 31, 2007

Record last verified: 2007-05

Locations

GB (1)