Plasmodium falciparum infection
Conditions
Interventions
Product Name: ChAd63 CS
Pharmaceutical Form: Solution for injection
Product Name: MVA CS
Pharmaceutical Form: Solution for injection
Product Name: ChAd63 ME-TRAP (AdCh63 ME-TRAP)
Pharmaceutical Form
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 7.2 Inclusion and Exclusion 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 challenge and completion of antimalarial treatment. • Willingness to take a curative anti-malaria regimen following challenge. • 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 48 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 P. falciparum malaria. • 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 challenge (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. • 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, thalassemia or thalassemia trait or any haematological condition that could affect susceptibility to malaria infection. • Pregnancy, lactation or intention to become pregnant during the study. • Contraindications to the use of all three proposed anti-malarial medications; Malarone, Riamet 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. • 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 participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main purpose of this study is to assess the protective effectiveness of four new vaccines against malaria in healthy volunteers. The vaccines are derived from two different types of virus which contain genetic information (DNA) from the malaria parasite. This genetic material produces a parasite component named CS or ME-TRAP. Both viruses are changed so that they are unable to multiply within the body. The first vaccine virus is a weakened version of a common cold virus which usually infects chimpanzees and is called an adenovirus. The vaccines made from this virus are called ChAd63 CS & ChAd63 ME-TRAP. The other virus is Modified Vaccinia Ankara Virus (MVA) which is a safer form of the virus previously widely used for smallpox vaccination. The vaccines made from this virus are called MVA CS & MVA ME-TRAP. Volunteers will receive varying vaccine regimens and will then be infected with malaria to see how effective the vaccines are at preventing malaria infection. This w;Secondary Objective: The secondary purpose of this study is to assess the safety and ability to stimulate the immune system of the four new malaria vaccines. ;Primary end point(s): Vaccine efficacy will be assessed by comparing the number of vaccinees who develop malaria infection and the time between malaria challenge and malaria diagnosis compared with unvaccinated controls. Volunteers will be diagnosed as having malaria according to the criteria in the protocol. ;Timepoint(s) of evaluation of this end point: The primary end point of the study will be evaluated when all volunteers who have undergone challenge have commenced treatment for malaria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The safety of the vaccine regimens will be assessed by analysing actively and passively collected data from clinical review of volunteers and laboratory measurements. The following parameters will be considered evidence of the impact of vaccination in inducing malaria-specific immune responses. (A) Interferon gamma ELISPOT. (B) Flow cytometry to measure T cell responses Other laboratory investigations including microarray analysis may be performed.;Timepoint(s) of evaluation of this end point: The secondary endpoints of the study will be evaluated when all data regarding safety and immunogenicity has been collected, cleaned and collated at the end of the study. | — |
Countries
United Kingdom
Contacts
Public ContactDr Alison Lawrie
University of Oxford
Outcome results
None listed