Study to Assess Efficacy of New Malaria Vaccine Candidates AdCh63 AMA1, MVA AMA1, AdCh63 MSP1, MVA MSP1, AdCh63 ME-TRAP & MVA ME-TRAP
March 25, 2011 updated by: University of Oxford
A Phase I/IIa Sporozoite Challenge Study to Assess the Protective Efficacy of New Malaria Vaccine Candidates AdCh63 AMA1, MVA AMA1, AdCh63 MSP1, MVA MSP1, AdCh63 ME-TRAP & MVA ME-TRAP
This study aims to test the safety and efficacy of six new malaria vaccines - AdCh63 AMA1, MVA AMA1, AdCh63 MSP1, MVA MSP1, AdCh63 ME-TRAP & MVA ME-TRAP.
These vaccines consist of inactivated viruses which have been modified - so they cannot reproduce (replicate) in humans, and also to include genetic material (genes) for malaria proteins which are expressed by the malaria parasite during both liver and blood stage infection.
The vaccines are designed to stimulate an immune response to these malaria proteins (immunogenicity describes the nature and magnitude of this immune response) and thus provide protection against malaria infection.
The protective efficacy of vaccines will be evaluated by challenging a small number of volunteers who have received the vaccines with malaria infection from the bites of infected mosquitos(sporozoite challenge).
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Anticipated)
52
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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London, United Kingdom, WC1E 6JB
- Hospital for Tropical Diseases Mortimer Market
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Oxford, United Kingdom, OX3 7LJ
- Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford
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Southampton, United Kingdom, SO16 6YD
- Wellcome Trust Clinical Research Facility, University of Southampton
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy adults aged 18 to 50 years
- 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 female volunteers, willingness to practice continuous effective contraception for the duration of the study.
- Agreement to refrain from blood donation during the course of the study
- Written informed consent
Exclusion Criteria:
- History of clinical P. falciparum malaria
- Travel to a malaria endemic region during the study period or within the preceding six months with a risk of malaria exposure.
- 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 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 & chloroquine
- Concomitant use with other drugs known to cause QT-interval prolongation (e.g. macrolides, quinolones, amiodarone etc)
- History of epilepsy
- History of arrhythmia or prolonged QT interval.
- Family history for sudden cardiac death.
- An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system 107
- 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 post vaccination
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- History of serious psychiatric condition that may affect participation in the study
- 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 in the 5 years preceding enrolment.
- Seropositive for hepatitis B surface antigen (HBsAg)
- Seropositive for hepatitis C virus (antibodies to HCV)
- Any clinically significant abnormal finding on biochemistry or haematology blood tests or urinalysis
- Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Group 1
1 dose of AdCh63 MSP1 and 1 dose MVA MSP1 followed by sporozoite challenge
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1 dose of AdCh63 MSP1 5 x 1010 vp intramuscularly and 1 dose MVA MSP1 2.5 x 108 pfu intramuscularly 8 weeks later (range 6-12 weeks) followed by sporozoite challenge 12-28 days later
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EXPERIMENTAL: Group 2
1 dose of AdCh63 AMA1 and 1 dose MVA AMA1 followed by sporozoite challenge
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1 dose of AdCh63 AMA1 5 x 1010 vp intramuscularly and 1 dose MVA AMA1 2.5 x 108 pfu intramuscularly 8 weeks later (range 6-12 weeks) followed by sporozoite challenge 12-28 days later
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EXPERIMENTAL: Group 3
1 dose of AdCh63 AMA1 and 1 dose AdCh63 MSP1 co-administered into separate arms followed by 1 dose of MVA AMA1 and 1 dose MVA MSP1 co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge
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1 dose of AdCh63 AMA1 5 x 1010 vp intramuscularly and 1 dose AdCh63 MSP1 5 x 1010 vp intramuscularly co-administered into separate arms followed 8 weeks later (range 6-12 weeks) by 1 dose of MVA AMA1 2.5 x 108 pfu intramuscularly and 1 dose MVA MSP1 2.5 x 108 pfu intramuscularly co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge 12-28 days later.
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EXPERIMENTAL: Group 4
1 dose of AdCh63 MSP1 and 1 dose AdCh63 ME-TRAP co-administered into separate arms followed by 1 dose of MVA MSP1 and 1 dose MVA ME-TRAP co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge
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1 dose of AdCh63 MSP1 5 x 1010 vp intramuscularly and 1 dose AdCh63 ME-TRAP 5 x 1010 vp intramuscularly co-administered into separate arms followed 8 weeks later (range 6-12 weeks) by 1 dose of MVA MSP1 2.5 x 108 pfu intramuscularly and 1 dose MVA ME-TRAP 2 x 108 pfu intramuscularly co-administered into separate arms (but the same arm as the corresponding AdCh63 vaccine) followed by sporozoite challenge 12-28 days later.
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OTHER: Group 5
Non-vaccinated controls for sporozoite challenge
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Non-vaccinated controls for sporozoite challenge
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Safety and efficacy of vaccine
Time Frame: Up to 18 months
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To assess if volunteers who receive the novel vaccine candidates; AdCh63 MSP1, MVA MSP1, AdCh63 AMA1, MVA AMA1, AdCh63 ME-TRAP and MVA ME-TRAP in heterologous prime boost regimens are protected wholly or partially against malaria infection in a sporozoite challenge model. This will be determined by noting the number of subjects who develop malaria infection and the time in hours between exposure and parasitaemia as detected by thick-film blood smear compared with controls. To assess the safety of the immunisation regimens alone and during co-administration. |
Up to 18 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Immunogenicity of vaccine
Time Frame: Up to 18 months
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To assess immunogenicity of the vaccine regimes by measuring IFN-γ ELISPOT, flow cytometry and antibody responses to MSP1, AMA1 and ME-TRAP antigens before and after malaria infection.
If there is evidence of partial or complete protection, we will explore immunological correlates of protective immunity.
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Up to 18 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2010
Primary Completion (ACTUAL)
March 1, 2011
Study Completion (ACTUAL)
March 1, 2011
Study Registration Dates
First Submitted
June 7, 2010
First Submitted That Met QC Criteria
June 10, 2010
First Posted (ESTIMATE)
June 11, 2010
Study Record Updates
Last Update Posted (ESTIMATE)
March 28, 2011
Last Update Submitted That Met QC Criteria
March 25, 2011
Last Verified
March 1, 2011
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VAC039
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