Plasmodium falciparum infection
Conditions
Interventions
Product Name: ChAdOx1 LS2
Pharmaceutical Form: Solution for injection
Product Name: MVA LS2
Pharmaceutical Form: Solution for injection
Sponsors
University of Oxford, CTRG
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 • For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination • Agreement to refrain from blood donation during the course of the study • Provide written informed consent to participate in the trial. Additional inclusion criteria for group 2 and control groups A&B • 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. • 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 31 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 clearly malaria endemic locality during the study period or within the preceding six months • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data as assessed by the investigator. This may include non-malaria adenovirus vectored experimental vaccine. If any volunteers in Group 2 undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC067 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. • Pregnancy, lactation or intention to become pregnant during the study. • 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). • Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. • 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. Additional exclusion criteria for group 2 and control groups A&B • Clinically significant disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia • Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin). • History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of new candidate malaria vaccines ChAdOx1 LS2 administered alone, and with MVA LS2 in a prime-boost regimen by the intramuscular routes in healthy malaria-naïve volunteers To assess the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of ChAdOx1 LS2 and MVA LS2 administered in prime-boost vaccination regimen against malaria sporozoite challenge, in healthy malaria-naïve volunteers. ; Secondary Objective: To assess cell-mediated immunogenicity generated in malaria naïve individuals of intramuscular prime-boost vaccination schedule with ChAdOx1 LS2 and MVA LS2. To assess the efficacy (measured as time to P. falciparum parasitemia assessed by blood slide, by PCR, and parasite density dynamics assessed by PCR) of ChAdOx1 LS2 and MVA LS2 administered in prime-boost vaccination regimenagainst malaria sporozoite challenge, in healthy malaria-naïve volunteers. ; Primary end point(s): 1. To assess the safety and tolerability of new candidate malaria vaccines ChAdOx1 LS2 administered alone, and with MVA LS2 in a prime-boost regimen by the intramuscular routes in healthy malaria-naïve volunteers 2. To assess the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of ChAdOx1 LS2 and MVA LS2 administered in prime-boost vaccination regimen against malaria sporozoite challenge, in healthy malaria-naïve volunteers. ; Timepoint(s) of evaluation of this end point: Evaluation of the adverse events following vaccination will begin as soon as the first vaccine is given, and will continue throughout the remainder of the trial. It will be assessed by analysing adverse event data collected from diary cards, clinical review of volunteers, and laboratory measurements. Any adverse events persisting at the end of the trial will be followed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To assess cell-mediated immunogenicity generated in malaria naïve individuals of intramuscular prime-boost vaccination schedule with ChAdOx1 LS2 and MVA LS2. 2. To assess the efficacy (measured as time to P. falciparum parasitemia assessed by blood slide, by PCR, and parasite density dynamics assessed by PCR) of ChAdOx1 LS2 and MVA LS2 administered in prime-boost vaccination regimen against malaria sporozoite challenge, in healthy malaria-naïve volunteers. ; 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 21 (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