E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Plasmodium Falciparum Malaria |
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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 |
The main purpose of this study is to assess the safety and effectiveness of two new vaccines against malaria in healthy volunteers.
The vaccines are two different types of virus which contain genetic information (DNA) from the malaria parasite. This genetic material produces a parasite component named MSP1. We will be checking the safety of different doses of one of the vaccines. 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 vaccine is called AdCh63 MSP1.
The other virus is Modified Vaccinia Ankara Virus, (MVA), which is a safer form of the virus previously widely used for smallpox vaccination. The vaccine is called MVA MSP1. The safety of the vaccines will also be assessed during a malaria challenge.
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess markers of the effectiveness of two new vaccines against malaria. We want to test the response of the human immune system to the vaccines. The vaccines help the body make an immune response against the malaria parasite, and so to test the effectiveness of the vaccine we will also expose a small group of volunteers to experimental malaria infection to see if the vaccine combination can prevent or delay malaria developing. We will take regular blood samples to see what effect the vaccines have had on the immune system.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Healthy adults 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 practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of vaccination and / or challenge • For males only, to use barrier contraception until three months after the last vaccination • Agreement to refrain from blood donation during the course of the study • Written informed consent
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E.4 | Principal exclusion criteria |
• Significant concern raised by GP in relation to participation • 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 a recombinant adenoviral and/or MVA vectored vaccine. • 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) • 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 • Contraindication to both anti-malarial drugs (Riamet® and chloroquine) o concomitant use with other drugs known to cause QT-interval prolongation, (e.g. macrolides, quinolones, amiodarone etc) • A predicted ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system • History of arrhythmia or congenital QT interval prolongation • Family history of sudden cardiac death • Any history of anaphylaxis in reaction to vaccination • Pregnancy, lactation or willingness/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 • 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. • Any history of malaria or • 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measures: -To assess the safety in healthy volunteers of two new candidate malaria vaccines, AdCh63 MSP1 and MVA MSP1. The safety of AdCh63 MSP1 when administered alone and in combination with MVA MSP1 will be assessed.
-To assess the safety of the prime-boost blood stage vaccine strategy following malaria sporozoite challenge.
The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events, including laboratory safety data, following vaccination (all groups) and sporozoite challenge (group 2C). The collection and interpretation of adverse event data including severity grading scales are summarised in Section 12 of the clinical trial protocol.
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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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 last volunteer |
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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 | 1 |
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 | 1 |
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 |