A Phase I/IIa Sporozoite Challenge Study to Assess the Efficacy of Candidate Combination Malaria Vaccine Approaches Using the ChAd63 and MVA Vectors Encoding the Antigens ME-TRAP, CS and AMA1
1 other identifier
interventional
48
1 country
3
Brief Summary
This is an open label, multi-centre phase I/IIa sporozoite-challenge trial to assess the safety, immunogenicity and efficacy of two combination ChAd63-MVA heterologous prime-boost vaccination regimens. All volunteers recruited will be healthy, malaria naïve adults aged between 18 and 45 years. To determine the efficacy of each of two combinations of heterologous prime-boost immunisation strategies:
- 1.ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS
- 2.ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2013
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 28, 2012
CompletedFirst Posted
Study publicly available on registry
November 30, 2012
CompletedStudy Start
First participant enrolled
January 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2013
CompletedNovember 11, 2013
November 1, 2013
9 months
November 28, 2012
November 8, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The effectiveness of ChAd63-MVA ME-TRAP combined with ChAd63-CS and ChAd63-MVA AMA1 at preventing malaria infection.
To assess the efficacy of each of two combinations of heterologous prime-boost immunisation strategies: 1. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS 2. ChAd63-MVA ME-TRAP combined with ChAd63-MVA CS and ChAd63-MVA AMA1 Kaplan-Meier analysis of time to blood stage infection in vaccinees compared to unvaccinated control volunteers. Comparison of the number of individuals who develop malaria infection between vaccinees and unvaccinated control volunteers.
Up to 30 days post challenge
Secondary Outcomes (1)
Safety and immunogenicity of ChAd63-MVA ME-TRAP, ChAd63-MVA CS, ChAd63-MVA AMA1.
Up to 7 months post first vaccination
Study Arms (4)
Group 4
ACTIVE COMPARATORUnvaccinated control volunteers who undergo controlled human malaria infection.
Group 3
ACTIVE COMPARATORControlled human malaria infection administered at an interval of approximately 8-12 months after the initial controlled human malaria infection that the volunteers received in the VAC045 clinical trial.
Group 2
ACTIVE COMPARATORIntramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp and ChAd63 AMA1 5 x 1010 vp followed by intramuscular administration of a mixture of MVA ME-TRAP 1.33 x 108 pfu and MVA CS 1.33 x 108 pfu and MVA AMA1 1.33 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later.
Group 1
ACTIVE COMPARATORIntramuscular administration of a mixture of ChAd63 ME-TRAP 5 x 1010 vp and ChAd63 CS 5 x 1010 vp, followed by intramuscular administration of a mixture of MVA ME-TRAP 2 x 108 pfu and MVA CS 2 x 108 pfu eight weeks later, followed by controlled human malaria infection 17-24 days later.
Interventions
Mixture of ChAd63 CS 5 x 1010 vp and ChAd63 ME-TRAP 5 x 1010 vp. Intramuscular needle injection.
Mixture of MVA CS 2 x 108 pfu and MVA ME-TRAP 2 x 108 pfu. Intramuscular needle injection.
Mixture of ChAd63 CS 5 x 1010 vp, ChAd63 ME-TRAP 5 x 1010 vp, and ChAd63 AMA1 5 x 1010 vp. Intramuscular needle injection.
Mixture of MVA CS 1.33 x 108 pfu, MVA ME-TRAP 1.33 x 108 pfu, and MVA AMA1 1.33 x 108 pfu. Intramuscular needle injection.
Approximately three weeks post MVA dosing.
Eligibility Criteria
You may qualify if:
- Healthy adults aged 18 to 45 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.
- Women only: Must practice continuous effective contraception for the duration of the study.
- Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
- Written informed consent to participate in the trial.
- Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment.
- Willingness to take a curative anti-malaria regimen following CHMI.
- For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (from at least day 6.5 post mosquito bite until anti-malarial treatment is completed).
- Answer all questions on the informed consent quiz correctly.
- Group 3 volunteers only: have been sterilely protected against malaria following CHMI after receiving ChAd63-MVA prime-boost vaccination in the VAC045 clinical trial
You may not qualify if:
- History of clinical malaria (any species).
- Travel to a malaria endemic region during the study period or within the preceding six months with significant risk of malaria exposure.
- Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- 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).
- Use of immunoglobulins or blood products within 3 months prior to enrolment.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon) or malaria infection.
- Any history of anaphylaxis post vaccination.
- History of clinically significant contact dermatitis.
- History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
- Pregnancy, lactation or intention to become pregnant during the study.
- Use of medications known to cause prolongation of the QT interval or to otherwise have a potentially clinically significant interaction with Riamet
- Any clinical condition known to prolong the QT interval
- History of cardiac arrhythmia, including clinically relevant bradycardia
- Disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
Wellcome Trust CRF, Southampton General Hospital
Southampton, Hampshire, SO16 6YD, United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, OX3 7LE, United Kingdom
Infection and Immunity Section, Imperial College of Science, Technology and Medicine
London, SW7 2AZ, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Adrian V S Hill, MD
University of Oxford
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 28, 2012
First Posted
November 30, 2012
Study Start
January 1, 2013
Primary Completion
October 1, 2013
Study Completion
October 1, 2013
Last Updated
November 11, 2013
Record last verified: 2013-11