| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary Objectives
To assess if volunteers who received AdCh63 ME-TRAP alone, as a homologous prime and boost, or as a heterologous boost with MVA ME-TRAP are protected wholly or partially against malaria infection in a sporozoite challenge model. This will be determined by noting the number of subjects who develop malaria infection and the time in hours between exposure and parasitaemia as detected by thick-film blood smear or clinical symptoms in the presence of positive PCR, and compared with controls.
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| E.2.2 | Secondary objectives of the trial |
Secondary Objectives
To measure the safety of the vaccination regimes and to measure ex-vivo and cultured IFN-g ELISPOT responses to the ME-TRAP antigens and anti-sporozoite antibodies before and after malaria infection. If there is evidence of partial or complete protection by the vaccinations then we will explore immunological correlates of protective immunity
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The volunteer must satisfy all the following criteria to be eligible for the study:
• Healthy adult aged 18 to 50 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 practise effective contraception throughout the study
• Agreement to refrain from blood donation during the course of the study
• Written informed consent
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| E.4 | Principal exclusion criteria |
The volunteer may not enter the study if any of the following apply:
• Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period.
• Prior receipt of an investigational malaria vaccine encoding ME-TRAP or any other investigational vaccine likely to impact on interpretation of the trial data
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• 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)
• Pregnancy, lactation or intention to become pregnant during the study
• Contraindication to both anti-malarial drugs (chloroquine)
o concomitant use with other drugs known to cause QT-interval prolongation, ( e.g. macrolides, quinolones, amiodarone etc)
o history of epilepsy
• An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system [58]
• History of arrhythmia or prolonged QT interval;
• positive family history for sudden death
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products, Kathon.
• History of clinically significant contact dermatitis
• Any history of anaphylaxis in reaction to vaccination
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition
• 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
• Seropositive for hepatitis B surface antigen (HBsAg)
• Seropositive for hepatitis C virus (antibodies to HCV)
• Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or may influence the result of the study, or the volunteer’s ability to participate in the study.
• History of clinical P. falciparum malaria
• Travel to a malaria endemic region during the study period or within the previous six months
• Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
• Any other finding which in the opinion of the investigators would significantly increase the risk of having an adverse outcome from participating in the protocol or impair interpretation of the study data.
Re-vaccination exclusion criteria
The following adverse events associated with vaccine immunisation constitute absolute contraindications to further administration of vaccine. If any of these events occur during the study, the subject must be withdrawn and followed until resolution of the event, as with any adverse event.
Anaphylactic reaction following administration of vaccine
Pregnancy
The following adverse events constitute contraindications to administration of vaccine at that point in time; if any one of these adverse events occurs at the time scheduled for vaccination, the subject may be vaccinated at a later date, or withdrawn at the discretion of the investigator. The subject must be followed until resolution of the event as with any adverse event
Acute disease at the time of vaccination. (Acute disease is defined as the presence of a moderate or severe illness with or without fever.) All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature of <37.5°C/99.5°F).
Temperature of 37.5°C (99.5°F) at the time of vaccination.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Evaluation Criteria
Definition of the Criteria
The protection against malaria infection in a sporozoite challenge model will be assessed by measuring the number of subjects who develop malaria infection and the time (in hours) between exposure and parasitaemia as detected by thick-film blood smear, and compared with controls.
End-points:
Primary: One thick smear positive for one or more morphologically-normal parasites during the 21 day observation period, OR
Secondary: Subject is manifesting typical clinical symptoms or signs of malaria in the opinion of the Chief Investigator (such as fever >37.5C, rigors, moderate or severe myalgia, in the absence of another obvious cause) and has negative blood smears but has a PCR result that is positive for malaria.
Parameters to be Measured
Clinical Symptoms
Definitions:
No solicited adverse events will be recorded, but the following predictable symptoms of malaria will be enquired about at each visit :
Symptoms of feverishness
Chills
Rigors
Sweats
Headache
Anorexia
Nausea / vomiting
Diarrhoea
Myalgia /Arthralgia
Low back pain
Subjects will be instructed to record their oral temperature with the thermometer provided should they feel feverish.
The subjects will be instructed to contact the investigator immediately should they manifest any signs or symptoms they perceive as serious.
Parasitological Parameters
The parasitaemia will be assessed by thick smears and PCR.
Method and Timing of Measurement
Clinical signs:
The clinical assessment and the check of vital signs will be performed and recorded at each timepoint from visit 4 to visit 29.
Parasitology parameters:
Blood smears and PCR will be performed for each volunteer, from visit 1 to visit 27. From D6 to D14, the samples will be taken twice a day (approximately 12 hourly).
After a positive blood film, blood samples will be collected daily until two consecutive negative thick smears are obtained. These will be examined by blood smear examination immediately. PCR analysis will also be done until the first positive thick smear.
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Secondary Evaluation Criteria
Immunological assays will be conducted according to the procedures established in the test laboratories. With the volunteers’ informed consent, any leftover cells and serum will be frozen for future immunological analysis of malaria-specific responses.
Tertiary Evaluation Criteria
Durability of immunity in protected individuals will be measured by a re-challenge and reassessing primary and secondary criteria as described above.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| Last visit of the last subject undergoing the trial |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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