E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Malaria (Plasmodium vivax) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Parasitic Diseases [C03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047665 |
E.1.2 | Term | Vivax malaria (benign tertian) |
E.1.2 | System Organ Class | 100000004862 |
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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 efficacy of the PvDBPII in Matrix M1 vaccine |
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E.2.2 | Secondary objectives of the trial |
To assess the humoral and cellular immunogenicity of PvDBPII in Matrix M1 vaccine candidate. To assess immunological readouts for association with a reduced parasite multiplication rate
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Healthy adult aged 18 to 45 years. • Red blood cells positive for the Duffy antigen/chemokine receptor (DARC). • Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PD). • Negative haemoglobinopathy screen • 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. • Women only: Must practice continuous effective contraception* for the duration of the study • Agreement to permanently refrain from blood donation • Written informed consent to participate in the trial. • Reachable (24/7) by mobile phone during the period between CHMI and completion of all antimalarial treatment. • Willing to take a curative anti-malarial regimen following CHMI. • Willing to reside in Oxford for the duration of the study, until antimalarials have been completed. • Answer all questions on the informed consent quiz correctly at first or second attempt.
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E.4 | Principal 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. • Current or planned treatment with long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). • Chronic use of antibiotics with antimalarial effects (e.g. tetracyclines for dermatologic patients, trimethoprim-sulfamethoxazole for recurrent urinary tract infections, etc.). • Weight less than 50kg, as measured at the screening visit • Receipt of immunoglobulins within the three months prior to planned administration of the vaccine candidate. Receipt of blood products (e.g., blood transfusion) at any time in the past. • Peripheral venous access unlikely to allow twice daily blood testing (as determined by the Investigator). • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. • Concurrent involvement in another clinical trial or planned involvement during the study period • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data or the P. vivax parasite as assessed by the Investigator.
• Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt during the study period • 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 allergic disease or reactions likely to be exacerbated by malaria infection. • History of clinically significant contact dermatitis • Any history of anaphylaxis in reaction to vaccinations • Pregnancy, lactation or intention to become pregnant during the study. • 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. • Any clinical condition known to prolong the QT interval. • History of cardiac arrhythmia, including clinically relevant bradycardia. • Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia. • Family history of congenital QT prolongation or sudden death. • Contraindications to the use of both of the proposed anti-malarial medications; Riamet Malarone. • 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 25 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 or (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). • Positive family history in both 1st AND 2nd degree relatives < 50 years old for cardiac disease. • Volunteers unable to be closely followed for social, geographic or psychological reasons. • Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. • 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. • 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) |
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 reactogenicity signs and symptoms for 7 days following the vaccination • Occurrence of unsolicited adverse events for 28 days following the vaccination • Change from baseline for safety laboratory measures for 28 days following vaccination • Occurrence of serious adverse events during the whole study duration
Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between the vaccinated volunteers and non-vaccinated, malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and reactogenicity will be monitored throughout the study as detailed above.
The efficacy evaluation using qPCR measurement of parasitaemia will begin at 7 days following blood-stage challenge and will continue until diagnosis or for up to 28 days post challenge if diagnosis is not made before then. |
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E.5.2 | Secondary end point(s) |
PvDBP_RII -specific immunogenicity will be assessed by a variety of immunological assays, with comparison before and after vaccination. The main outcome measures will be humoral and B cell responses to the P. vivax Duffy-binding protein (PvDBP) – total IgG, isotypes and avidity; T cell responses to PvDBP by flow cytometry assays and in vitro functional PvDBP_RII inhibitory binding assays. Other established and exploratory immunology assays may be carried out, including through collaboration with other specialist laboratories.
The relationship between PMR in vaccinated subjects and anti-PvDBP_RII antibody responses induced by the PvDBPII in Matrix M1 vaccine and PMR will also be assessed.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
immunogenicity data will be collected at pre-specified timepoints throughout the study. |
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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 | Yes |
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 | 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 | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Unvaccinated volunteers who undergo malaria |
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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
| 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 | No |
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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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 | 5 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 30 |