Safety, Immunogenicity, and Impact of MVA85A, on the Immunogenicity of the EPI Vaccines

NCT00480454 | Completed Phase 1 DMC

• 1 other identifier: TB012
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

This study is preliminary to proving that this vaccine could protect against tuberculosis in humans. Although there is no proven data to show that infants will benefit directly from participation in this study by being protected against TB, MVA85A protection of mice, guinea pigs and monkeys against tuberculosis is encouraging. It is hoped that the information gained from this study will contribute to the development of a safe and effective TB vaccine for HIV negative and positive individuals. Participants in this study will benefit by having information about their general health status, and the rigorous follow up visit that could enhance early detection and management of medical conditions that might arise in the course of the study.

Conditions

TB

Keywords

TB; Tuberculosis; Infants; EPI

Outcome Measures

Primary Outcomes (1)

• Dose selection, safety and immunogenicity of MVA85A vaccines in 4 month old healthy Gambian infants

  one year

Secondary Outcomes (1)

• Impact of MVA85A on the immunogenicity of EPI vaccines (DTwPHib, Hep B) and vice versa when administered simultaneously to children who have had BCG vaccine within the first two weeks of life.

  One year

Study Arms (2)

1

ACTIVE COMPARATOR

Stage 1 would require 12 per group low dose and 12 per group high dose (total 72)

Biological: MVA 85A

2

ACTIVE COMPARATOR

Stage 2 would require 48 per group (total 144)

Biological: MVA 85A

Interventions

MVA 85A BIOLOGICAL

intradermal vaccine

Also known as: TB vaccine, modified vaccinia virus Ankara

1; 2

Eligibility Criteria

• Age: 2 Months - 3 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy infants aged 2 - 3 months
• Recorded BCG vaccination within first two weeks of life with typical BCG scar on the left arm
• Receiving standard EPI immunizations according to national immunization programme (DTwPHib at 2/3/4 months, OPV at birth, 1, 2 and 3 months, Hep B at birth, 2 \& 4 months)
• Written informed consent by parent / guardian

You may not qualify if:

• Any clinically significant abnormal finding on screening from biochemistry or haematology
• Any AIDS defining illness
• Prior receipt of a recombinant MVA or Fowlpox vaccine, or other experimental vaccine
• Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 2 weeks 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 6 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
• History of \> 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
• Any other on-going chronic illness requiring hospital specialist supervision
• Administration of immunoglobulins and/or any blood products within one month preceding the planned administration of the vaccine candidate
• Any history of anaphylaxis in reaction to vaccination
• Research Physician's assessment of lack of willingness by parents to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the infant's risk of suffering an adverse outcome
• Likelihood of travel away from the study area
• Untreated malaria infection

Sponsors & Collaborators

• University of Oxford: lead
• Medical Research Council: collaborator

Study Sites (1)

MRC

Banjul, The Gambia

Location

Related Publications (4)

• 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

MeSH Terms

Conditions

Tuberculosis

Interventions

MVA 85A; MVA Pfs25-IMX313 malaria vaccine

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: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 30, 2007
• First Posted: May 31, 2007
• Study Start: October 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: February 9, 2010

Record last verified: 2010-02

Locations

TH (1)