Plasmodium falciparum Infection
Conditions
Interventions
Product Name: ChAd63 ME-TRAP (AdCh63 ME-TRAP)
Pharmaceutical Form: Solution for injection
Product Name: ChAd63 CS
Pharmaceutical Form: Solution for injection
Product Name: MVA ME-TRAP
Pharmaceutical
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The volunteer must satisfy all the following criteria to be eligible for the study: • 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 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: The volunteer may not enter the study if any of the following apply: • 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. • Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. For Group 3 participants, and Group 1 and 2 participants undergoing rechallenge, this exclusion criterion does not extend to the vaccines previously received for the VAC045 and VAC052 trials. • 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 • Family history of congenital QT prolongation or sudden death • Contraindications to the use of all three proposed anti-malarial medications; Riamet, Malarone and Chloroquine. • 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) with positive PCR for hepatitis C at screening. • An estimated, ten year risk of fatal cardiovascular disease of =5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system.76 • Positive family history in 1st and 2nd degree relatives < 50 years old for cardiac disease. • Volunteers unable to be closely followed for social, geographic or psychological reasons. • Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. • Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a clinical trial in which healthy volunteers will be administered experimental malaria vaccines. One group of volunteers will receive a vaccination composed of a mixture of the ChAd63 ME-TRAP and ChAd63 CS vaccines, followed by another vaccination 8 weeks later with a mixture of the MVA CS and MVA ME-TRAP vaccines. Another group will receive a vaccination composed of a mixture of the ChAd63 ME-TRAP, ChAd63 CS and ChAd63 AMA1 vaccines, followed by another vaccination 8 weeks later with a mixture of the MVA CS, MVA ME-TRAP and MVA AMA1 vaccines. The principal research objective is to measure how well each of these two new malaria vaccine strategies act to prevent malaria disease. This is called efficacy. We will measure it by infecting volunteers with malaria and seeing whether the vaccines change how long it takes for malaria disease to develope.;Secondary Objective: One secondary objective is to assess the safety of each of these vaccination strategies. We will assess this by analysing all the medical symptoms and signs and any abnormalities on blood tests that occur in volunteers who have received the vaccines. The other secondary objective is to assess the immune responses to these vaccination strategies. We will do this by taking blood from volunteers who have received the vaccines and doing tests on it, such as measuring the number of immune cells that are induced by the vaccines.;Primary end point(s): Efficacy of the Group 1 vaccination regimen will be assessed by comparing the number of volunteers who develop blood stage infection, and the time to blood stage infection following CHMI, between Group 1 volunteers and control volunteers (Group 4). Efficacy of the Group 2 vaccination regimen will be assessed in the same way, using results of Group 2 volunteers and the control Group (Group 4). Volunteers will be diagnosed as having blood stage malaria infection acording to the criteria in the protocol.;Timepoint(s) of evaluation of this | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety of vaccination will be assessed by analysing adverse event data collected from diary cards, clinical review of volunteers, and laboratory measurements. Interferon gamma ELISPOT and flow cytometry to measure T cell responses will be used to assess the malaria-specific immune responses induced by vaccination. Other laboratory investigations including microarray analysis may be performed.;Timepoint(s) of evaluation of this end point: Adverse events for assessment of safety will be collected and evaluated from the time of enrolment of the volunteer until their final visit. Any adverse events persisting at the end of the trial will be followed up until there is a satisfactory resolution or stabilisation occurs or until a non study related causality is found. Immunology investigations will be collected on blood specimens taken from volunteers across the course of their participation in the trial. | — |
Countries
United Kingdom
Contacts
Public ContactDr Alison Lawrie
University of Oxford
Outcome results
None listed