Plasmodium falciparum infection
Conditions
Interventions
Product Name: ChAd63 ME-TRAP (AdCh63 ME-TRAP)
Pharmaceutical Form: Solution for injection
Product Name: MVA ME-TRAP
Pharmaceutical Form: Solution for injection
Sponsors
University of Oxford, CTRG
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 • 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. • 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. • Willingness to provide a named person who may be contacted in the event it is not possible to locate the volunteer following CHMI 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 52 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 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 undergo rechallenge, this exclusion criterion does not extend to the vaccines previously received in the VAC066 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). • Inability of the study team to contact the volunteer’s GP to confirm medical history and safety to participate • 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 (described in section 9.6.1). • 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. • 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 could affect susceptibility to malaria infection. • 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. • Contraindications to the use of both Riamet and Malarone. • Any clinical condition known to prolong
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy (occurrence of P. falciparum malaria parasitemia, assessed by PCR) of intramuscular vaccination followed by intravenous boosting with ChAd63 and MVA encoding ME-TRAP, against malaria sporozoite challenge, in healthy malaria-naïve volunteers • To assess the safety of intramuscular vaccination followed by intravenous boosting with ChAd63 and MVA encoding ME-TRAP, in healthy malaria-naïve volunteers ;Secondary Objective: • To assess cellular immune responses generated in malaria naïve individuals of vaccination schedules incorporating intramuscular prime dose(s) followed by intravenous booster with ChAd63 and MVA encoding ME-TRAP • To assess the efficacy as measured by time to infection and parasite growth rates, of intramuscular vaccination followed by intravenous boosting with ChAd63 and MVA encoding ME-TRAP, against malaria sporozoite challenge, in healthy malaria-naïve volunteers;Primary end point(s): The primary efficacy outcome measure will be the number of individuals completely protected against malaria compared to controls. Completely protected individuals are those who do not, by Day 21 following sporozoite challenge, develop blood stage infection as defined in the protocol. The proportion protected will be compared individually to controls by Fisher exact tests to ask if there is more protection in the vaccine group than controls. This CHMI study will use a highly sensitive PCR assay for the detection malaria parasite (nucleic acids)as the diagnostic endpoint. This is emerging as standard practice across CHMI centres due to its superior sensitivity to microscopy to allow for earlier and more accurate malaria diagnosis. The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed: • Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination • Occurrence of solicited systemic r | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in immune response before and after vaccination will be assessed by immunological assays. The key measure of immunogenicity will be ELISPOT to enumerate IFN-? producing T cells. Secondary end points for vaccine efficacy include time to P. falciparum parasitemia assessed by PCR, and parasite density dynamics assessed by PCR These measures enable more powerful distinction, than the use of sterile efficacy rates, between the performance of different vaccination regimens, and between individuals receiving the same vaccination regimen. ;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 relevant malaria diagnostic endpoints and PCR thresholds: 20 parasites per ml; time to 500 parasites per ml; time to 1000 parasites per ml as well as time to malaria diagnosis - >10,000 parasites per ml or 1000 parasites per/ml in the presence of malaria symptoms. | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Adrian Hill
University of Oxford
Outcome results
None listed