E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Plasmodium falciparum infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Parasitic Diseases [C03] |
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 |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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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 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.
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E.4 | Principal 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 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 the QT interval and existing contraindication to the use of Malarone. • Family history of congenital QT prolongation or sudden death and existing contraindication to the use of Malarone. • History of cardiac arrhythmia, including clinically relevant bradycardia and existing contraindication to the use of Malarone. • Positive family history in both 1st and 2nd degree relatives < 50 years old for cardiac disease. • Volunteer unable to be closely followed for social, geographic or psychological reason • Inability of the study team to contact the volunteer’s GP to confirm medical history and safety to participate
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | 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 up until there is a satisfactory resolution or stabilisation occurs or until a non study related causality is found.
Evaluation for blood stage malaria infection will occur from Day 6.5 following malaria challenge to Day 21 following malaria challenge. |
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E.5.2 | 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.
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E.5.2.1 | 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. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Unvaccinated volunteers who undergo malaria challenge |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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 | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 5 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |