Plasmodium Vivax Infection Clinical Trial
A Clinical Study to Assess the Safety and Feasibility of Controlled Blood-stage Plasmodium Vivax Human Malaria Infection Through Experimental Inoculation of Cryopreserved Infected Erythrocytes in Healthy Thai Adults
The primary objectives of this study are to assess the safety and feasibility of blood-stage controlled human P. vivax malaria infection (CHMI) in healthy adult Thai volunteers through experimental injection of cryopreserved P. vivax infected erythrocytes, and to choose the optimal inoculation dose for future P. vivax CHMI studies. In this study, blood-stage CHMI will be conducted in 8 volunteers per inoculum stock who will be infected with P. vivax by experimental injection with cryopreserved P. vivax infected erythrocytes, which were collected from the controlled human Plasmodium vivax malaria infection model through experimental sporozoite infection in Thai adults (NCT04083508) . As there are currently 2 stocks of inocula from 2 volunteers in the NCT04083508 study, which have different quantity and stage of parasites. The total number of volunteers of this study would be up to 16 (8 volunteers per inocula stock). The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases, and will be treated according to the Research Proposal.
This study is a blood-stage P. vivax human challenge study with the primary aim of assessing the safety and feasibility of a challenge model using two banks of cryopreserved P. vivax infected erythrocytes produced from NCT04083508 study to identify the dose of the inocula to be used in the future CHMI studies. Sixteen healthy Thai adults, aged between 18 and 55 years will be recruited at the Clinical Therapeutics Unit (CTU) in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok. The overall period of each volunteer's participation will be 13 months: 2-week screening process prior to the Day 0 challenge, about 2-week inoculum process until reaching malarial treatment criteria, and follow-up period for 1 year after malarial treatment. All inclusion and exclusion criteria will be checked to ensure eligibility criteria have been met prior to Day 0. Volunteers will be admitted to the hospital one day prior to challenged day. All eligible volunteers will have physical examinations. Serum pregnancy test (woman only), malaria diagnosis, complete blood count (CBC), and biochemistry will be tested. Glucose -6-phospate dehydrogenase (G6PD) test and malaria immunological profiles will be tested for baseline information. On the challenged day (Day 0), four different doses of inoculum (one whole vial,1:5 dilution, 1:10 dilution, and 1:20 dilution) will be assessed. Each dose of inoculum will be tested in 2 volunteers to identify the lowest concentration producing a reliable infection within a practicable timeframe. Therefore, there will be 8 volunteers enrolled per inoculum bank. The assessment will be repeated in each inoculum bank. There are 2 inoculum banks so 16 volunteers will be enrolled into this study. From Day 1 after challenge, the volunteers will be assessed once daily until malaria qPCR becomes positive. The assessment includes a clinical well-being check, physical examination, vital signs, and blood drawn for parasitaemia (malaria blood film, qPCR, and gametocyte qPCR) and membrane feeding to assess the transmissibility of gametocyte. Malaria immunology and CBC will be performed on day 4 and the day that qPCR become positive. After qPCR become positive the clinical well-being will be continue. Blood will be drawn twice daily to monitor blood parasitemia and membrane feeding to assess the transmissibility of gametocyte. Malaria immunology, CBC, and blood biochemistry will be performed on day that volunteer reach malaria treatment criteria. A study physician will immediately prescribe malarial treatment with chloroquine according to local standard guideline. Blood will be collected to test for malaria (blood films and qPCR) once daily until clinically recovered and wo consecutive malaria blood films are negative (completing of the chloroquine treatment course) and volunteers will be discharged from the hospital. If any volunteer reaches day 21 post-challenge without a positive malaria blood film, they shall be started on 3-day course of antimalaria (chloroquine). If a volunteer withdraws/is withdrawn from the study after challenge but before reaching the criteria for malaria treatment, then a complete, appropriate, curative course of antimalarial therapy must be completed After discharge from the hospital, there will be out-patient visit on day 7, 28, 60, 90, 180, and 1 year post malarial treatment initiated. Blood will be collected to detect malaria parasites by blood film and qPCR, and for malaria gametocyte qPCR, membrane feeding assays (MFA), malaria immune response, CBC, and biochemistry according to the study protocol. Data analysis The safety of the CHMI will be assessed by descriptive analysis of the frequency, incidence and nature of adverse events and serious adverse events arising during the study. Since this is a feasibility study conducted in 2 volunteers per dosing group, formal statistical hypothesis testing will not be used for most analyses due to the limited sample size, and only a brief Statistical Analysis Plan (SAP) will be developed and finalized prior to database lock. The study will be conducted in accordance with the current approved protocol, the International Conference on Harmonisation-Good Clinical Practice (ICH GCP), relevant regulations, and standard operating procedures. Data will be evaluated for compliance with the protocol and accuracy in relation to source documents. Following written standard operating procedures, the monitors will verify that the clinical study is conducted and data are generated, documented and reported in compliance with the protocol. ;