A Study of MVA85A, in Asymptomatic Volunteers Infected With TB, HIV or Both

NCT00480558 | Completed Phase 1 DMC

• 1 other identifier: TB011
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the safety of MVA85A in asymptomatic volunteers in South Africa who are infected with M.tb, HIV or both. A single vaccination with MVA85A, when administered at a dose of 5 x 107pfu intradermally, is safe and highly immunogenic in mycobacterially naïve individuals, BCG vaccinated individuals and M.tb latently infected individuals. We will use the same vaccination regime in this study. Participants will be defined as being infected with M.tb.if they have a positive Elispot response to ESAT6 or CFP10. Participants will be defined as being infected with HIV.if they have a positive HIV rapid test (Determine®, Abbott Laboratories) followed by a positive HIV ELISA result. Participants will be identified from the general population living in Worcester, Western Cape, South Africa

Conditions

HIV Infections; TB

Keywords

HIV; MVA85A; TB; Tuberculosis; Human Immunodeficiency Virus; Safety; Immunogenicity; Efficacy; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• To assess the safety of a single intradermal injection of 5 x 107p.f.u. MVA85A.

  One year

Secondary Outcomes (1)

• To assess the effect of a single vaccination with MVA85A in asymptomatic participants who are infected with M.Tb or HIV or both on the immune response, both to antigen 85A (the antigen in the vaccine) and to ESAT6/CFP10 antigens (M.tb specific).

  One year

Study Arms (4)

1

ACTIVE COMPARATOR

Group 1: M. tb

Biological: MVA 85A

2

ACTIVE COMPARATOR

Group 2: HIV (not on antiretrovirals \[ARV\])

Biological: MVA 85A

3

ACTIVE COMPARATOR

Group 3: M. tb and HIV (not on ARV)

Biological: MVA 85A

4

ACTIVE COMPARATOR

Group 4: M. tb and HIV (on ARV)

Biological: MVA 85A

Interventions

MVA 85A BIOLOGICAL

Modified vaccinia Ankara virus expressing antigen 85A from M. tuberculosis. Dose is 5x10\^7

Also known as: TB Vaccine, modified vaccinia virus Ankara

1; 2; 3; 4

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• For all groups:
• Asymptomatic adults aged 21 to 50 years
• Chest x-ray normal with no evidence of past/present TB infection or disease or any other clinically significant finding
• Resident in or near Worcester for the duration of the vaccination study
• Willingness to allow the investigators to discuss the volunteer's medical history with the
• volunteer's usual doctor or HIV physician
• Agreement to refrain from blood donation during the course of the study
• Willing and able to provide written informed consent
• Willingness to undergo an HIV test
• For the M.Tb infected- and M.Tb/HIV coinfected- groups:
• Screening Elispot positive (more than 50 spots/million PBMC): for either the pool of ESAT6 peptides and/or the pool of CFP10 peptides and screening Elispot positive for PPD.
• Positive Mantoux test. (\>10mm induration)
• For the HIV infected and M.Tb/HIV coinfected groups:
• HIV antibody positive; diagnosed at least 3 months previously
• CD4 count \>300; nadir CD4 not \< 300

You may not qualify if:

• For all groups:
• Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis that is considered to be clinically significant
• Any previous ARV therapy
• 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.)
• Pregnant/lactating female and any female who is willing or intends to become pregnant during the study
• Any AIDS defining illness
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
• 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) and or hepatitis C (antibodies to HCV)
• 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)
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any history of anaphylaxis in reaction to vaccination
• PI assessment of lack of willingness to participate and comply with all requirements of the protocol

Sponsors & Collaborators

• University of Oxford: lead
• University of Cape Town: collaborator

Study Sites (1)

University Cape Town

Cape Town, South Africa

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

• Scriba TJ, Tameris M, Smit E, van der Merwe L, Hughes EJ, Kadira B, Mauff K, Moyo S, Brittain N, Lawrie A, Mulenga H, de Kock M, Makhethe L, Janse van Rensburg E, Gelderbloem S, Veldsman A, Hatherill M, Geldenhuys H, Hill AV, Hawkridge A, Hussey GD, Hanekom WA, McShane H, Mahomed H. A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected adults. Am J Respir Crit Care Med. 2012 Apr 1;185(7):769-78. doi: 10.1164/rccm.201108-1548OC. Epub 2012 Jan 26.

  PMID: 22281831 DERIVED

MeSH Terms

Conditions

HIV Infections; Tuberculosis; Acquired Immunodeficiency Syndrome

Interventions

MVA 85A; MVA Pfs25-IMX313 malaria vaccine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Slow Virus Diseases

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: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 30, 2007
• First Posted: May 31, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 28, 2011

Record last verified: 2011-03

Locations

ZA (1)