Plasmodium falciparum infection
Conditions
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 (defined as: Established use of oral, injected or implanted hormonal contraceptives; Intrauterine Device or Intrauterine System; Barrier methods (condoms or diaphragm with additional spermicide); Male sterilisation (with appropriate post-vasectomy documentation of absence of sperm in the ejaculate); True abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]. • 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. 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 58 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • 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. If any volunteers in Group 1, 2 & 3 undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC059 trial • 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 and existing contraindication to the use of Malarone • Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone • 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 standard UK units every week. • Suspected or known injecting drug abuse in the 5 years preceding enrolment. • Hepatitis B surface antigen (HBsAg) detected in serum. • Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study). • An estimated, ten year risk of fatal cardiovascular disease of =5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system. • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a clinical trial in which healthy volunteers will be administered experimental malaria vaccines. Two groups of volunteers will receive vaccination with the leading malaria vaccine candidate, RTS,S/AS01. One group will receive 3 standard doses of RTS,S/AS01, while another will receive 2 standard doses of RTS,S/AS01 with a fractional 3rd dose (consisting of one fifth of the standard dose). Two other groups will receive vaccination with RTS,S, but they will also receive concurrent vaccination with ChAd63 ME-TRAP with the first RTS,S and MVA ME-TRAP with the next two doses of RTS,S. One of these two groups will receive 3 standard doses of RTS,S, the other will receive a fractional 3rd dose. Vaccines will be delivered at 4 week intervals (ie. At 0, 4 & 8 weeks). The vaccine schedule containing RTS,S alone, and ChAd63 ME-TRAP and MVA ME-TRAP have been tested independently in clinical trials, however, the vaccine schedule containing both RTS,S/AS01, ChAd63 ME-TRAP and MVA ME-TRAP c;Secondary Objective: The 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. Another secondary objective is to assess the length of time taken to malaria diagnosis as a secondary measure of vaccine effect.;Primary end point(s): To assess the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of a combination immunization regimen of ChAd63 ME-TRAP and MVA ME-TRAP delivered concomitantly with RTS,S/AS01B, at either full standard dose or with a fractional 3rd dose (1/5 standard dose), and of RTS,S/AS01B alone with a fractional 3rd dose, against malaria sporozoite challenge, in healthy malaria-naïve volunteers. To assess the safety of a combination immunization regimen of ChAd63 ME-TRAP and MVA ME-TRAP delivered concomitantly with RTS,S | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Interferon gamma ELISPOT and flow cytometry to measure T cell responses will be used to assess the malaria-specific immune responses induced by vaccination. ELISAs will be used to assess humoral immune responses. Other laboratory investigations including microarray analysis may be performed. PCR data will be collected from Day 6.5 to day 23 (or until malaria diagnosis) to establish time to 20 parasites per ml and time to 500 parasites per ml.;Timepoint(s) of evaluation of this end point: Immunology investigations will be collected on blood specimens taken from volunteers across the course of their participation in the trial. PCR data will be collected from Day 6.5 to day 23 (or until malaria diagnosis) to establish time to 20 parasites per ml and time to 500 parasites per ml. | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Adrian Hill
University of Oxford
Outcome results
None listed