Plasmodium Vivax InfectionMIST2NCT05071079
A Controlled Human Vivax Malaria Infection Study Through Inoculation of Infected Erythrocytes
A study testing An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum, An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum and An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum in people with Plasmodium Vivax Infection, run by University of Oxford at 1 site in Thailand.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Vivax Infection
- What is being tested?
- An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum, An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum and An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteThailand
- Study dates
- 23 May 2022to Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- The volunteer must meet all of the following criteria to be eligible for the study:
- Healthy Thai adult aged 20 to 55 years with weight at least 50 kg.
- Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
- Women only: Must practice continuous effective contraception for the duration of study period until 3 months post-challenge.
- COVID-19 vaccination at least two doses of COVID-19 vaccines approved by WHO.
- Agreement to refrain from blood donation during the course of the study and for 1 year after the initiation of antimalarial treatment.
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- Willing to be admitted in the Hospital for Tropical Diseases for clinical monitoring, until antimalarial treatment is completed and their symptoms are settling.
- Willing to take a curative antimalarial treatment following CHMI.
- Willing to reside in Bangkok and its vicinity for 2 months after malarial treatment initiation.
- Able to read and write in Thai.
- Provide written informed consent to participate in the trial
- Answer all questions on the informed consent quiz correctly
- Educational level: has at least an undergraduate degree
Who cannot join
- The volunteer must NOT enter the study if any of the following apply:
- Positive malaria qPCR OR malaria film
- Presence of any medical condition (either physical or psychological) which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
- Presence of chronic disease or chronically use of medication
- Use of systemic antibiotics with known antimalarial activity in the 30 days before challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Use of immunoglobulins or blood products (e.g. blood transfusion) at any time in the 1 year preceding enrolment
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- Receipt of an investigational product, any vaccine in the 30 days preceding enrolment (D0), or planned receipt 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.
- Any confirmed, or suspected immunosuppressive, or immunodeficient state, including HIV infection, asplenia, history of splenectomy, recurrent, severe infections, and chronic infection
- Immunosuppressant medication within the past 6 months preceding enrolment (D0) (inhaled and topical steroids are allowed)
- History of allergic disease or reactions likely to be exacerbated by malaria infection
- Female participant who is pregnant as evidenced by positive beta-human chorionic gonadotropin (β-HCG) test, lactating, or planning pregnancy during the course of the study
- Contraindications to the use of antimalarial treatment (e.g. chloroquine, atovaquone / proguanil or dihydroartemisinin/piperaquine)
- Use of medications known to have a potentially clinically significant interaction with the antimalarial drug that will be used in this study (chloroquine, atovaquone / proguanil or dihydroartemisinin/piperaquine)
- Known existing positive family history in both 1st AND 2nd degree relatives < 50 years old for cardiac disease
- History of cardiac arrhythmia, including clinically relevant bradycardia
- Family history of congenital QT prolongation or sudden death
- Any clinical condition, including using medications, known to prolong the QT interval.
- Screening electrocardiogram (ECG) demonstrates a QTc interval ≥ 450 ms.
- Suspected or known or history of alcohol abuse
- Suspected or known or history of drug abuse.
- Concurrently participating in another clinical study, at any time during the study period
- Haemoglobin < 11 g/dL
- Positive hepatitis B surface antigen or seropositive for hepatitis C virus
- Finding on safety laboratory values as defined below:
- Abnormal AST (AST > 40 U/L for male, and > 32 U/L for female [upper normal range])
- Abnormal ALT (ALT > 41 U/L for male, and > 33 U/L for female [upper normal range])
- Abnormal serum creatinine (Scr) (Creatinine [Cr] > 1.17 mg/dL for male, and > 0.95 mg/dL for female [upper normal range])
- Abnormalities corrected calcium and magnesium blood levels
- Blood group Rhesus negative
- Blood incompatibility to the inoculum
- Positive for COVID-19 diagnosed by RT-PCR
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Thailand1 site, 1 recruiting
- Recruiting
Faculty of Tropical Medicine
Bangkok, 10400
Borimas Hanboonkunupakarn, MD, +66 (0)8 6 9705705, borimas@tropmedres.ac
Podjanee Jittamala, MD, +66 (0)8 1956 3371, podjanee@tropmedres.ac
About this study
Official title: 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 each 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) . There are currently 4 stocks of inocula from 6 volunteers in the NCT04083508 study, which have differing quantities and stages of parasites.
The total number of volunteers of this study will be up to 48 (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 funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A.
Read the detailed description
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 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.
Forty-eight healthy Thai adults, aged between 20 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 (women 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 currently 4 inoculum banks and 20 volunteers have been enrolled to date so 28 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 becomes positive the monitoring of clinical well-being will continue. Blood will be drawn twice daily to monitor blood parasitaemia and allow 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.
When the malaria slide positivity and/or symptoms thresholds have been reached study physician will immediately prescribe antimalarial treatment with chloroquine according to local standard guidelines. Blood will be collected to test for malaria (blood films and qPCR) once daily until clinically recovered and two consecutive malaria blood films are negative (completing of the chloroquine treatment course) and volunteers will be discharged from the hospital. Before discharge from the hospital, HIV-I and HIV-II antigen, HBV and HCV serology, COVID-19 testing (RT-PCR) and COVID-19 serology test will be carried out to confirm that volunteers did not acquire COVID-19 during their inpatient stay.
If any volunteer reaches day 21 post-challenge without a positive malaria blood film, they shall be started on 3-day course of antimalarial treatment (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 visits on day 7, 28, 60, 90, 180, and 1 year post antimalarial treatment initiation. Blood will be collected to detect malaria parasites by blood film and qPCR, and for malaria gametocyte qPCR, membrane feeding assays (MFA), HIV-I and HIV-II antigen, HBV, HCV, CMV, and EBV, 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.
- Conditions
- Plasmodium Vivax Infection
- Being tested
- An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum, An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum, An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum, An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculum
- Keywords
- controlled human malaria infection, Plasmodium Vivax Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculumBiological
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with whole dose blood-stage inoculum (neat)
An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculumBiological
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:5 dilution blood-stage inoculum
An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculumBiological
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:10 dilution blood-stage inoculum
An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculumBiological
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:20 dilution blood-stage inoculum
| Study group | Role | What they receive |
|---|---|---|
| Challenge with whole dose blood-stage inoculum (neat) | Experimental | Whole dose: one whole vial, containing approximately 0.5 mL of red blood cells, will be reconstituted in 0.9% saline, to a total volume of 5 mL Receives: Biological: An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum |
| Challenge with 1:5 dilution blood-stage inoculum | Experimental | 1:5 dilution: one fifth of a vial (containing approximately 0.1 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL. Receives: Biological: An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum |
| Challenge with 1:10 dilution blood-stage inoculum | Experimental | 1:10 dilution: one tenth of a vial (containing approximately 0.05 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL. Receives: Biological: An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum |
| Challenge with 1:20 dilution blood-stage inoculum | Experimental | 1:20 dilution: one twenties of a vial (containing approximately 0.025 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL. Receives: Biological: An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incident of treatment-emergent adverse events of blood-stage controlled human P. vivax malaria infection
Measured by (serious) adverse event (AE) occurrences
Measured: Through study completion, over one year
Choosing the optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration.
The optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration
Measured: Through study completion, over one year
Feasibility of primary P. vivax blood-stage CHMI, as measured by successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)
Measured: Through study completion, over one year
Secondary outcomes (4)
Geometric mean and standard deviation/error of Pvs25 gene transcript copy number/microL at each time point
Measured by qPCR in experimental P. vivax infection through blood-stage challenge
Measured: Challenge day; day 1 to 5 or up to day of treatment and during subsequent days of follow-up through study completion, over one year
Transmissibility of gametocytes from the infected volunteer to Anopheles mosquito vector
Measured by gametocytes from the infected volunteer to Anopheles mosquito vector using Membrane feeding assay
Measured: Through study completion, over one year
Cellular Immune response to primary P. vivax infection (frequencies, percentages (%), and expression level of mononuclear cells)
Immune cells including Innate and adaptive immune cells react and express during the PV infection (profile and frequency)
Measured: Day-1, Day 2, Day 5, Day of blood donation, DayRx7, DayRx28, DayRx90, DayRx1 year
Level of antibodies and cytokines responses to primary P. vivax infection during different phase of infection
Immune cells defense PV antigen by determining the level of antibody response and inflammatory cytokine
Measured: Day-1, Day 2, Day 5, Day of blood donation, DayRx7, DayRx28, DayRx90, DayRx1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2021
- Study start23 May 2022
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Vivax InfectionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Controlled Plasmodium vivax human malaria infection through experimental inoculation of cryopreserved infected erythrocytes in healthy Thai adults, with a randomized double blind design.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- Nicholas Day, MD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05071079
- Sponsor's protocol ID
- MAL21001
- Acronym
- MIST2
- Status last verified
- Jan 2026
- First submitted
- 28 Jul 2021
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Volunteer's data and results from blood analyses stored in our database may be shared with other researchers to use in the future. However, the other researchers will not be given any information that could identify the subject.
Publications
Baird JK. Evidence and implications of mortality associated with acute Plasmodium vivax malaria. Clin Microbiol Rev. 2013 Jan;26(1):36-57. doi: 10.1128/CMR.00074-12.
PubMed 23297258Rahimi BA, Thakkinstian A, White NJ, Sirivichayakul C, Dondorp AM, Chokejindachai W. Severe vivax malaria: a systematic review and meta-analysis of clinical studies since 1900. Malar J. 2014 Dec 8;13:481. doi: 10.1186/1475-2875-13-481.
PubMed 25486908Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM. Vivax malaria: neglected and not benign. Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):79-87.
PubMed 18165478Watson J, Taylor WRJ, Bancone G, Chu CS, Jittamala P, White NJ. Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria. PLoS Negl Trop Dis. 2018 Apr 20;12(4):e0006440. doi: 10.1371/journal.pntd.0006440. eCollection 2018 Apr.
PubMed 29677199Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, Caridha D, Zeng Q, Reichard GA, Ockenhouse C, Bennett J, Walker LA, Ohrt C, Melendez V. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J. 2013 Jun 20;12:212. doi: 10.1186/1475-2875-12-212.
PubMed 23782898Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med. 2013 Oct 3;369(14):1381-2. doi: 10.1056/NEJMc1301936. No abstract available.
PubMed 24088113Grabowsky M. The billion-dollar malaria moment. Nature. 2008 Feb 28;451(7182):1051-2. doi: 10.1038/4511051a. No abstract available.
PubMed 18305524Moorthy VS, Newman RD, Okwo-Bele JM. Malaria vaccine technology roadmap. Lancet. 2013 Nov 23;382(9906):1700-1. doi: 10.1016/S0140-6736(13)62238-2. Epub 2013 Nov 14. No abstract available.
PubMed 24239252Mueller I, Shakri AR, Chitnis CE. Development of vaccines for Plasmodium vivax malaria. Vaccine. 2015 Dec 22;33(52):7489-95. doi: 10.1016/j.vaccine.2015.09.060. Epub 2015 Oct 1.
PubMed 26428453Payne RO, Griffin PM, McCarthy JS, Draper SJ. Plasmodium vivax Controlled Human Malaria Infection - Progress and Prospects. Trends Parasitol. 2017 Feb;33(2):141-150. doi: 10.1016/j.pt.2016.11.001. Epub 2016 Dec 10.
PubMed 27956060Keith JA, Agostini Bigger L, Arthur PA, Maes E, Daems R. Delivering the promise of the Decade of Vaccines: opportunities and challenges in the development of high quality new vaccines. Vaccine. 2013 Apr 18;31 Suppl 2:B184-93. doi: 10.1016/j.vaccine.2012.12.032.
PubMed 23598480Pronker ES, Weenen TC, Commandeur H, Claassen EH, Osterhaus AD. Risk in vaccine research and development quantified. PLoS One. 2013;8(3):e57755. doi: 10.1371/journal.pone.0057755. Epub 2013 Mar 20.
PubMed 23526951Knezevic I, Moorthy V, Sheets R. WHO consultation on clinical evaluation of vaccines, 17-18 July 2014, WHO Headquarters, Geneva, Switzerland. Vaccine. 2015 Apr 21;33(17):1999-2003. doi: 10.1016/j.vaccine.2015.01.056. Epub 2015 Mar 4.
PubMed 25749249Stanisic DI, McCarthy JS, Good MF. Controlled Human Malaria Infection: Applications, Advances, and Challenges. Infect Immun. 2017 Dec 19;86(1):e00479-17. doi: 10.1128/IAI.00479-17. Print 2018 Jan.
PubMed 28923897Roestenberg M, Hoogerwerf MA, Ferreira DM, Mordmuller B, Yazdanbakhsh M. Experimental infection of human volunteers. Lancet Infect Dis. 2018 Oct;18(10):e312-e322. doi: 10.1016/S1473-3099(18)30177-4. Epub 2018 Jun 18.
PubMed 29891332
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05071079
- Acronym / sponsor ID
- MIST2 / MAL21001
- Conditions
- Plasmodium Vivax Infection
- Keywords
- controlled human malaria infection, Plasmodium Vivax Infection
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- 23 May 2022 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 7 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 each 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) . There are currently 4 stocks of inocula from 6 volunteers in the NCT04083508 study, which have differing quantities and stages of parasites.
The total number of volunteers of this study will be up to 48 (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 funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A.
Detailed description
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 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.
Forty-eight healthy Thai adults, aged between 20 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 (women 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 currently 4 inoculum banks and 20 volunteers have been enrolled to date so 28 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 becomes positive the monitoring of clinical well-being will continue. Blood will be drawn twice daily to monitor blood parasitaemia and allow 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.
When the malaria slide positivity and/or symptoms thresholds have been reached study physician will immediately prescribe antimalarial treatment with chloroquine according to local standard guidelines. Blood will be collected to test for malaria (blood films and qPCR) once daily until clinically recovered and two consecutive malaria blood films are negative (completing of the chloroquine treatment course) and volunteers will be discharged from the hospital. Before discharge from the hospital, HIV-I and HIV-II antigen, HBV and HCV serology, COVID-19 testing (RT-PCR) and COVID-19 serology test will be carried out to confirm that volunteers did not acquire COVID-19 during their inpatient stay.
If any volunteer reaches day 21 post-challenge without a positive malaria blood film, they shall be started on 3-day course of antimalarial treatment (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 visits on day 7, 28, 60, 90, 180, and 1 year post antimalarial treatment initiation. Blood will be collected to detect malaria parasites by blood film and qPCR, and for malaria gametocyte qPCR, membrane feeding assays (MFA), HIV-I and HIV-II antigen, HBV, HCV, CMV, and EBV, 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Controlled Plasmodium vivax human malaria infection through experimental inoculation of cryopreserved infected erythrocytes in healthy Thai adults, with a randomized double blind design.
| Arm | Type | Receives |
|---|---|---|
| Challenge with whole dose blood-stage inoculum (neat) | Experimental | Biological: An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculumWhole dose: one whole vial, containing approximately 0.5 mL of red blood cells, will be reconstituted in 0.9% saline, to a total volume of 5 mL |
| Challenge with 1:5 dilution blood-stage inoculum | Experimental | Biological: An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum1:5 dilution: one fifth of a vial (containing approximately 0.1 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL. |
| Challenge with 1:10 dilution blood-stage inoculum | Experimental | Biological: An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum1:10 dilution: one tenth of a vial (containing approximately 0.05 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL. |
| Challenge with 1:20 dilution blood-stage inoculum | Experimental | Biological: An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculum1:20 dilution: one twenties of a vial (containing approximately 0.025 mL of red blood cells) will be reconstituted in 0.9% saline, to a total volume of 5 mL. |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Healthy Thai adult aged 20 to 55 years with weight at least 50 kg.
- Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
- Women only: Must practice continuous effective contraception for the duration of study period until 3 months post-challenge.
- COVID-19 vaccination at least two doses of COVID-19 vaccines approved by WHO.
- Agreement to refrain from blood donation during the course of the study and for 1 year after the initiation of antimalarial treatment.
Key exclusion criteria (32 listed)
- Positive malaria qPCR OR malaria film
- Presence of any medical condition (either physical or psychological) which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
- Presence of chronic disease or chronically use of medication
- Use of systemic antibiotics with known antimalarial activity in the 30 days before challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
- Use of immunoglobulins or blood products (e.g. blood transfusion) at any time in the 1 year preceding enrolment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculumAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with whole dose blood-stage inoculum (neat) | Biological | Challenge with whole dose blood-stage inoculum (neat) |
| An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculumAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:5 dilution blood-stage inoculum | Biological | Challenge with 1:5 dilution blood-stage inoculum |
| An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculumAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:10 dilution blood-stage inoculum | Biological | Challenge with 1:10 dilution blood-stage inoculum |
| An inoculum of malaria parasitised red blood cells with 1:20 dilution blood-stage inoculumAn inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:20 dilution blood-stage inoculum | Biological | Challenge with 1:20 dilution blood-stage inoculum |
Primary outcome
Incident of treatment-emergent adverse events of blood-stage controlled human P. vivax malaria infection
Time frame: Through study completion, over one year
Measured by (serious) adverse event (AE) occurrences
Choosing the optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration.
Time frame: Through study completion, over one year
The optimal inoculation dose for future P. vivax CHMI studies, which will be the lowest concentration that produces a reliable infection within a comparable timeframe as compare to the highest concentration
Feasibility of primary P. vivax blood-stage CHMI, as measured by successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)
Time frame: Through study completion, over one year
4 secondary outcomes
Geometric mean and standard deviation/error of Pvs25 gene transcript copy number/microL at each time point
Time frame: Challenge day; day 1 to 5 or up to day of treatment and during subsequent days of follow-up through study completion, over one year
Transmissibility of gametocytes from the infected volunteer to Anopheles mosquito vector
Time frame: Through study completion, over one year
Cellular Immune response to primary P. vivax infection (frequencies, percentages (%), and expression level of mononuclear cells)
Time frame: Day-1, Day 2, Day 5, Day of blood donation, DayRx7, DayRx28, DayRx90, DayRx1 year
Level of antibodies and cytokines responses to primary P. vivax infection during different phase of infection
Time frame: Day-1, Day 2, Day 5, Day of blood donation, DayRx7, DayRx28, DayRx90, DayRx1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
- Background: PubMed 23297258Baird JK. Evidence and implications of mortality associated with acute Plasmodium vivax malaria. Clin Microbiol Rev. 2013 Jan;26(1):36-57. doi: 10.1128/CMR.00074-12.
- Background: PubMed 25486908Rahimi BA, Thakkinstian A, White NJ, Sirivichayakul C, Dondorp AM, Chokejindachai W. Severe vivax malaria: a systematic review and meta-analysis of clinical studies since 1900. Malar J. 2014 Dec 8;13:481. doi: 10.1186/1475-2875-13-481.
- Background: PubMed 18165478Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM. Vivax malaria: neglected and not benign. Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):79-87.
- Background: PubMed 29677199Watson J, Taylor WRJ, Bancone G, Chu CS, Jittamala P, White NJ. Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria. PLoS Negl Trop Dis. 2018 Apr 20;12(4):e0006440. doi: 10.1371/journal.pntd.0006440. eCollection 2018 Apr.
- Background: PubMed 23782898Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, Caridha D, Zeng Q, Reichard GA, Ockenhouse C, Bennett J, Walker LA, Ohrt C, Melendez V. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J. 2013 Jun 20;12:212. doi: 10.1186/1475-2875-12-212.
- Background: PubMed 24088113Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med. 2013 Oct 3;369(14):1381-2. doi: 10.1056/NEJMc1301936. No abstract available.
- Background: PubMed 18305524Grabowsky M. The billion-dollar malaria moment. Nature. 2008 Feb 28;451(7182):1051-2. doi: 10.1038/4511051a. No abstract available.
- Background: PubMed 24239252Moorthy VS, Newman RD, Okwo-Bele JM. Malaria vaccine technology roadmap. Lancet. 2013 Nov 23;382(9906):1700-1. doi: 10.1016/S0140-6736(13)62238-2. Epub 2013 Nov 14. No abstract available.
- Background: PubMed 26428453Mueller I, Shakri AR, Chitnis CE. Development of vaccines for Plasmodium vivax malaria. Vaccine. 2015 Dec 22;33(52):7489-95. doi: 10.1016/j.vaccine.2015.09.060. Epub 2015 Oct 1.
- Background: PubMed 27956060Payne RO, Griffin PM, McCarthy JS, Draper SJ. Plasmodium vivax Controlled Human Malaria Infection - Progress and Prospects. Trends Parasitol. 2017 Feb;33(2):141-150. doi: 10.1016/j.pt.2016.11.001. Epub 2016 Dec 10.
- Background: PubMed 23598480Keith JA, Agostini Bigger L, Arthur PA, Maes E, Daems R. Delivering the promise of the Decade of Vaccines: opportunities and challenges in the development of high quality new vaccines. Vaccine. 2013 Apr 18;31 Suppl 2:B184-93. doi: 10.1016/j.vaccine.2012.12.032.
- Background: PubMed 23526951Pronker ES, Weenen TC, Commandeur H, Claassen EH, Osterhaus AD. Risk in vaccine research and development quantified. PLoS One. 2013;8(3):e57755. doi: 10.1371/journal.pone.0057755. Epub 2013 Mar 20.
- Individual participant dataSharing planned: Yes. Volunteer's data and results from blood analyses stored in our database may be shared with other researchers to use in the future. However, the other researchers will not be given any information that could identify the subject.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicholas Day, MD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing An inoculum of malaria parasitised red blood cells with whole dose blood-stage inoculum, An inoculum of malaria parasitised red blood cells with 1:5 dilution blood-stage inoculum and An inoculum of malaria parasitised red blood cells with 1:10 dilution blood-stage inoculum in people with Plasmodium Vivax Infection, run by University of Oxford at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicholas Day, MD (+66 (0)2 354 9170 ext. 2020, nickd@tropmedres.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incident of treatment-emergent adverse events of blood-stage controlled human P. vivax malaria infection (time frame: Through study completion, over one year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05071079, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026.