A Study to Assess the Effectiveness of a New Malaria Vaccine Candidate by Infecting Vaccinated Volunteers With Malaria Parasites

This study has been completed.
Sponsor:
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00890760
First received: April 29, 2009
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

Malaria affects around 515 million people each year, about a million of whom die from the disease. It is a major problem for those who live in affected areas as well as for travellers to affected areas. There is a great need for a safe, effective malaria vaccine. The purpose of this study is to test 2 new vaccination regimes that include a new malaria vaccine candidate, for their ability to prevent malaria infection.

The vaccines are different types of virus which contain genetic information (DNA) from the malaria parasite. This genetic material is named ME-TRAP. The aim is to use these viruses to help the body make an immune response against the malaria parasite. Both viruses are inactivated so that they are unable to multiply within the body.

The first vaccine virus is a weakened version of a common cold virus. Such adenoviruses occur in many strain types and commonly infect chimpanzees as well as people and this vaccine uses a strain originally derived from a chimpanzee. The vaccine is called AdCh63 ME-TRAP.

The other virus is Modified Vaccinia Ankara Virus, (MVA), which is a safer form of the vaccine virus previously widely used for smallpox vaccination. The vaccine is called MVA ME-TRAP.

This study will enable the investigators to assess:

  1. The ability of different vaccine combinations to prevent malaria infection
  2. The safety of the vaccine combinations in healthy volunteers
  3. The response of the human immune system to the vaccines

Condition Intervention Phase
Malaria
Biological: AdCh63 ME-TRAP
Biological: MVA ME-TRAP
Other: Sporozoite challenge
Biological: Mixture of AdCh63 ME-TRAP and MVA ME-TRAP intramuscularly
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Assessment of Protection Against Malaria by Sporozoite Challenge of Healthy Adults Vaccinated With AdCh63 ME-TRAP and MVA ME-TRAP

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Vaccine prevention (partial or complete) of malaria infection by sporozoite challenge [ Time Frame: Approxiamately 5-16 months following last intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of vaccine [ Time Frame: Approxiamately 5-16 months following last intervention ] [ Designated as safety issue: Yes ]

Enrollment: 55
Study Start Date: March 2009
Study Completion Date: February 2011
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
AdCh63 ME-TRAP prime followed by MVA ME-TRAP boost 8 weeks later and challenged by sporozoite 3 weeks after boost
Biological: AdCh63 ME-TRAP
5 x 10*10 vp IM
Biological: MVA ME-TRAP
2 x 10*8 pfu ID
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 2
AdCh63 ME-TRAP alone followed by sporozoite challenge 3 weeks later
Biological: AdCh63 ME-TRAP
5 x 10*10 vp IM
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 3
Non-vaccinated Control for Groups 1 and 2 challenged with sporozoite
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 4
AdCh63 ME-TRAP prime followed by MVA ME-TRAP boost 8 weeks later and challenged by sporozoite 11 weeks after boost
Biological: AdCh63 ME-TRAP
5 x 10*10 vp IM
Biological: MVA ME-TRAP
2 x 10*8 pfu ID
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 5
AdCh63 ME-TRAP prime followed by MVA ME-TRAP boost 8 weeks later and challenged by sporozoite 3 weeks after boost
Biological: AdCh63 ME-TRAP
5 x 10*10 vp IM
Biological: MVA ME-TRAP
2 x 10*8 pfu ID
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 6
Protected volunteers from Group 1 re-challenged with sporozoite after 6 months
Biological: AdCh63 ME-TRAP
5 x 10*10 vp IM
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 7
Non vaccinated control for Groups 4-6, 8-10 challenged with sporozoite
Other: Sporozoite challenge
Infected mosquito bite
Experimental: Group 8
3 vaccinations of mixture formulation AdCh63 ME-TRAP and MVA ME-TRAP give at 8 weeks interval each followed by sporozoite challenge 3 weeks after last vaccination
Other: Sporozoite challenge
Infected mosquito bite
Biological: Mixture of AdCh63 ME-TRAP and MVA ME-TRAP intramuscularly
AdCh63 ME-TRAP 5 x 10*10 vp MVA ME-TRAP 2 x 10*8 pfu
Experimental: Group 9
2 vaccinations of mixture formulation AdCh63 ME-TRAP and MVA ME-TRAP give at 8 weeks interval followed by sporozoite challenge 3 weeks after last vaccination
Other: Sporozoite challenge
Infected mosquito bite
Biological: Mixture of AdCh63 ME-TRAP and MVA ME-TRAP intramuscularly
AdCh63 ME-TRAP 5 x 10*10 vp MVA ME-TRAP 2 x 10*8 pfu
Experimental: Group 10
3 vaccinations of mixture formulation AdCh63 ME-TRAP and MVA ME-TRAP give at 4 weeks interval each followed by sporozoite challenge 3 weeks after last vaccination
Other: Sporozoite challenge
Infected mosquito bite
Biological: Mixture of AdCh63 ME-TRAP and MVA ME-TRAP intramuscularly
AdCh63 ME-TRAP 5 x 10*10 vp MVA ME-TRAP 2 x 10*8 pfu

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner
  • For females only: willingness to practise effective contraception throughout the study
  • Agreement to refrain from blood donation during the course of the study
  • Written informed consent

Exclusion Criteria:

  • Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period.
  • Prior receipt of an investigational malaria vaccine encoding ME-TRAP or any other investigational vaccine likely to impact on interpretation of the trial data
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
  • Pregnancy, lactation or intention to become pregnant during the study
  • Contraindication to both anti-malarial drugs (Riamet® and chloroquine)

    o concomitant use with other drugs known to cause QT-interval prolongation, ( e.g. macrolides, quinolones, amiodarone etc)

  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products, Kathon.
  • History of clinically significant contact dermatitis
  • Any history of anaphylaxis in reaction to vaccination
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  • History of serious psychiatric condition
  • Any other serious chronic illness requiring hospital specialist supervision
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
  • Suspected or known injecting drug abuse
  • Seropositive for hepatitis B surface antigen (HBsAg)
  • Seropositive for hepatitis C virus (antibodies to HCV)
  • Seropositive for simian adenovirus 63 (antibodies to AdCh63) at a titre > 1: 200 ( EXCEPT CONTROL VOLUNTEERS)
  • Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer's ability to participate in the study.
  • History of clinical P. falciparum malaria
  • Travel to a malaria endemic region during the study period or within the previous six months
  • Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
  • Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the protocol or impair interpretation of the study data.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890760

Locations
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
Oxford, Headington, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Adrian VS Hill, D.Phil, FRCP University of Oxford
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Adrian VS Hill, Centre for Clinical Vaccinology and Tropical Medicine University of Oxford
ClinicalTrials.gov Identifier: NCT00890760     History of Changes
Other Study ID Numbers: MAL 034
Study First Received: April 29, 2009
Last Updated: November 28, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
Malaria
Vaccine

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections

ClinicalTrials.gov processed this record on October 23, 2014