Plasmodium vivax malaria MedDRA version: 20.0 Level: LLT Classification code 10047665 Term: Vivax malaria (benign tertian) System Organ Class: 100000004862
Conditions
Interventions
Product Name: PvDBPII
Pharmaceutical Form: Solution for injection
Product Name: Matrix-M1
Pharmaceutical Form: Solution for injection
Sponsors
University of Oxford / Clinical Trials and Research Governance
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 12 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. • 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 fol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;Main Objective: To assess the safety and efficacy of the PvDBPII in Matrix M1 vaccine;Secondary Objective: 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 ;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. ;Timepoint(s) of evaluation of this end point: immunogenicity data will be collected at pre-specified timepoints throughout the study. | — |
Countries
United Kingdom
Contacts
Public ContactAngela Minassian
University of Oxford
Outcome results
None listed