Plasmodium Vivax InfectionPhase 2MIST3NCT05380388
A Safety, Immunogenicity and Efficacy Study of PvRII/Matrix-M in Healthy Thai Adults Living in Thailand ( MIST3 )
A Phase 2 study testing Malaria Vaccine and HBV vaccine in people with Plasmodium Vivax Infection and Malaria Vaccine, run by University of Oxford at 1 site in Thailand.
Trial summary
This project is the third part of a 5-year research program entitled "Malaria Infection Studies in Thailand (MIST)" and known as MIST3. MIST3's primary objectives are to assess the safety of the PvRII/Matrix-M vaccine candidate in healthy adult Thai volunteers and to establish whether the PvRII/Matrix-M vaccine can… 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, Malaria Vaccine
- What is being tested?
- Malaria Vaccine and HBV vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteThailand
- Study dates
- 1 Jan 2027to 30 Dec 2027
- Phase
- Phase 2
- 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
- Healthy Thai adults aged 20 to 55 years
- Minimum educational level of high school or equivalent
- Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
- Women only: Must practice continuous effective contraception for the duration of the study period until 3 months post-challenge.
- Agreement to refrain from blood donation during the study and for 1 year after the initiation of antimalarial treatment.
- Willing to be admitted to the Hospital for Tropical Diseases for clinical monitoring as required by the protocol until antimalarial treatment is completed and their symptoms are settling, willing to take a curative antimalarial treatment following CHMI, and willing to reside in Bangkok and its vicinity for 2 months after malarial treatment initiation.
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- 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
- Completed COVID-19 vaccination with 2 doses of any WHO-approved vaccine
Who cannot join
- Positive malaria qPCR OR malaria film prior to vaccination and challenge
- Presence of any medical condition (either physical or psychological) that, in the judgment of the investigator, would place the participant at undue risk (including the history of clinically significant contact dermatitis) or interfere with the results of the study (e.g., underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
- Presence of chronic disease or chronic use of medication
- Prior receipt of other investigational vaccine which is likely to impact the interpretation of the trial data 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) or plan to use during the study (inhaled and topical steroids are allowed)
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- 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, or who is 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 potentially clinically significant interaction with the antimalarial drugs that will be used in this study (chloroquine, atovaquone/proguanil, or dihydroartemisinin/piperaquine)
- History of cardiac arrhythmia, including clinically relevant bradycardia or Known existing positive family history in both 1st AND 2nd-degree relatives < 50 years old for cardiac disease
- Family history of congenital QT prolongation or sudden death
- Any clinical condition, including using medications known to prolong the QT interval or screening electrocardiogram (ECG), demonstrates a QTc interval ≥ 450 ms.
- Suspected or known history of alcohol abuse or history of drug abuse.
- Concurrently participating in another clinical study, at any time during the study period
- Positive hepatitis B surface antigen or seropositive for hepatitis C virus, or HIV
- Finding on safety laboratory values as defined below:
- Abnormal ALT [>upper normal range]
- Abnormal serum creatinine [>upper normal range]
- Clinically significant abnormalities in corrected calcium and magnesium blood levels
- Haemoglobin < 11 g/dL
- Blood group Rhesus negative
- Blood incompatibility to the inoculum
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
- Any history of anaphylaxis in reaction to vaccinations
- Vaccination and re-vaccination exclusion criteria
- 1. Acute disease at the time of vaccination. (acute disease is defined as the presence of a moderate or severe illness with or without fever).
- The following adverse events associated with vaccine immunisation constitute absolute contraindications to further vaccine administration. If any of these events occur during the study, the participant must be withdrawn and followed until the resolution of the event, as with any adverse event:
- Anaphylactic reaction following administration of the vaccine
- Pregnancy
- The following constitute absolute contraindications to CHMI:
- Acute disease, defined as a moderate or severe illness with or without fever
- Pregnancy
- 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)
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
Faculty of Tropical Medicine
Bangkok, 10400
Kittiyod Poovorawan, MD, +(662)3069100-9 ext. 3160-2, kittiyod.poo@mahidol.ac.th
About this study
Official title: A Phase II Clinical Study to Assess the Safety, Immunogenicity, and Efficacy of Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvRII/Matrix-M in Healthy Thai Adults Living in Thailand
This project is the third part of a 5-year research program entitled "Malaria Infection Studies in Thailand (MIST)" and known as MIST3. MIST3's primary objectives are to assess the safety of the PvRII/Matrix-M vaccine candidate in healthy adult Thai volunteers and to establish whether the PvRII/Matrix-M vaccine can demonstrate a reduced parasite multiplication rate in vaccinated volunteers compared to a controlled group (placebo vaccine) in a blood-stage controlled human malaria infection model. This study will recruit up to 36 eligible healthy volunteers aged 20-55 in Thailand at the Faculty of Tropical Medicine, Mahidol University. Eighteen volunteers will receive three doses of the PvRII/Matrix-M candidate vaccine, and 18 volunteers will receive three doses of the placebo vaccine. Safety and immunogenicity will be evaluated after each dose as per protocol. Approximately four weeks after receiving the third vaccination, 24 volunteers will undergo blood-stage CHMI with Plasmodium vivax. The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases and treated according to the Research Proposal Submission Form.
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
Summary of trial design: Phase II, double-blinded, randomized controlled trial with CHMI, designed to assess the safety, immunogenicity, and protective efficacy of PvRII/Matrix-M vaccine.
Overview: This is a randomized controlled single-centre Phase II P. vivax blood-stage CHMI trial to assess the safety, immunogenicity, and efficacy of the candidate malaria vaccine PvRII/Matrix-M.
Healthy Thai adults aged between 20 and 55 years will be recruited and randomized at the Faculty of Tropical Medicine, Mahidol University in Bangkok.
Vaccination group: Up to 18 healthy adults aged between 20 and 55 years will be recruited. These volunteers will receive three doses of the PvRII/Matrix-M vaccine intramuscularly at months 0, 1, and 6.
Approximately three to four weeks post-boost (3rd vaccination), 12 volunteers will undergo P. vivax blood-stage CHMI, induced by injection of P. vivax infected erythrocytes.
Control group: Up to 18 healthy adults aged between 20 and 55 years will be recruited. These volunteers will receive three doses of HBV vaccine intramuscularly at months 0, 1, and 6.
12 volunteers will undergo P. vivax blood-stage CHMI, induced by injection of P. vivax infected erythrocytes.
Volunteers will have blood taken at regular intervals following vaccination and in the post-CHMI period to assess the immune response to vaccination and subsequent challenge, as well as parasite growth dynamics and gametocytaemia.
Close monitoring will continue until volunteers meet the criteria for treatment or until 28 days after the challenge, when treatment will be started empirically.
Therapy will be with a standard course of chloroquine where not contraindicated. As infection will be induced via intravenous injection of blood-stage parasites, there will be no liver-stage infection and no hypnozoite formation, thereby eliminating the need for radical cure with primaquine therapy. Follow-up at the study site will be up to 1 year after antimalarial treatment.
- Conditions
- Plasmodium Vivax Infection, Malaria Vaccine
- Being tested
- Malaria Vaccine, HBV vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Malaria VaccineBiological
Also called PvRII/Matrix-M
blood stage Plasmodium vivax malaria vaccine
HBV vaccineBiological
HBV Vaccine
| Study group | Role | What they receive |
|---|---|---|
| Malaria Vaccine | Experimental | PvRII/Matrix-M month 0, month 1, month 6 Receives: Biological: Malaria Vaccine |
| control | Other | HBV vaccine month 0, month 1, month 6 Receives: Biological: HBV vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
solicited local adverse event
occurrence of solicited local reactogenicity signs and symptoms
Measured: 7 days following each vaccination
solicited systemic adverse event
occurrence of solicited systemic reactogenicity signs and symptoms
Measured: 7 days following each vaccination
unsolicited adverse events
Occurrence of unsolicited adverse events
Measured: 28 days following each vaccination
safety laboratory measures
Number of participants with abnormal laboratory test results
Measured: 28 days following each vaccination
serious adverse events
Occurrence of serious adverse events during the whole study duration
Measured: through study completion, an average of 1 year
feasibility of primary P. vivax blood-stage CHMI
successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)
Measured: within 21 days following CHMI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2022
- Study start1 Jan 2027 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized placebo-controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University
- Responsible party
- Sponsor
- Investigators
- Nicholas Day, MD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05380388
- Sponsor's protocol ID
- MAL22004
- Acronym
- MIST3
- Status last verified
- Mar 2026
- First submitted
- 13 Apr 2022
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: With participant's consent, suitably anonymised clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future.
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Study to Assess the Safety, Immunogenicity, and Efficacy of Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvRII/Matrix-M in Healthy Thai Adults Living in Thailand
- ClinicalTrials.gov ID
- NCT05380388
- Acronym / sponsor ID
- MIST3 / MAL22004
- Conditions
- Plasmodium Vivax Infection, Malaria Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol University
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 18 May 2022 (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.
This project is the third part of a 5-year research program entitled "Malaria Infection Studies in Thailand (MIST)" and known as MIST3. MIST3's primary objectives are to assess the safety of the PvRII/Matrix-M vaccine candidate in healthy adult Thai volunteers and to establish whether the PvRII/Matrix-M vaccine can demonstrate a reduced parasite multiplication rate in vaccinated volunteers compared to a controlled group (placebo vaccine) in a blood-stage controlled human malaria infection model. This study will recruit up to 36 eligible healthy volunteers aged 20-55 in Thailand at the Faculty of Tropical Medicine, Mahidol University. Eighteen volunteers will receive three doses of the PvRII/Matrix-M candidate vaccine, and 18 volunteers will receive three doses of the placebo vaccine. Safety and immunogenicity will be evaluated after each dose as per protocol. Approximately four weeks after receiving the third vaccination, 24 volunteers will undergo blood-stage CHMI with Plasmodium vivax. The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases and treated according to the Research Proposal Submission Form.
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
Summary of trial design: Phase II, double-blinded, randomized controlled trial with CHMI, designed to assess the safety, immunogenicity, and protective efficacy of PvRII/Matrix-M vaccine.
Overview: This is a randomized controlled single-centre Phase II P. vivax blood-stage CHMI trial to assess the safety, immunogenicity, and efficacy of the candidate malaria vaccine PvRII/Matrix-M.
Healthy Thai adults aged between 20 and 55 years will be recruited and randomized at the Faculty of Tropical Medicine, Mahidol University in Bangkok.
Vaccination group: Up to 18 healthy adults aged between 20 and 55 years will be recruited. These volunteers will receive three doses of the PvRII/Matrix-M vaccine intramuscularly at months 0, 1, and 6.
Approximately three to four weeks post-boost (3rd vaccination), 12 volunteers will undergo P. vivax blood-stage CHMI, induced by injection of P. vivax infected erythrocytes.
Control group: Up to 18 healthy adults aged between 20 and 55 years will be recruited. These volunteers will receive three doses of HBV vaccine intramuscularly at months 0, 1, and 6.
12 volunteers will undergo P. vivax blood-stage CHMI, induced by injection of P. vivax infected erythrocytes.
Volunteers will have blood taken at regular intervals following vaccination and in the post-CHMI period to assess the immune response to vaccination and subsequent challenge, as well as parasite growth dynamics and gametocytaemia.
Close monitoring will continue until volunteers meet the criteria for treatment or until 28 days after the challenge, when treatment will be started empirically.
Therapy will be with a standard course of chloroquine where not contraindicated. As infection will be induced via intravenous injection of blood-stage parasites, there will be no liver-stage infection and no hypnozoite formation, thereby eliminating the need for radical cure with primaquine therapy. Follow-up at the study site will be up to 1 year after antimalarial treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Malaria Vaccine | Experimental | Biological: Malaria VaccinePvRII/Matrix-M month 0, month 1, month 6 |
| control | Other | Biological: HBV vaccineHBV vaccine month 0, month 1, month 6 |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Healthy Thai adults aged 20 to 55 years
- Minimum educational level of high school or equivalent
- Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
- Women only: Must practice continuous effective contraception for the duration of the study period until 3 months post-challenge.
- Agreement to refrain from blood donation during the study and for 1 year after the initiation of antimalarial treatment.
Key exclusion criteria (34 listed)
- Positive malaria qPCR OR malaria film prior to vaccination and challenge
- Presence of any medical condition (either physical or psychological) that, in the judgment of the investigator, would place the participant at undue risk (including the history of clinically significant contact dermatitis) or interfere with the results of the study (e.g., underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
- Presence of chronic disease or chronic use of medication
- Prior receipt of other investigational vaccine which is likely to impact the interpretation of the trial data 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
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 |
|---|---|---|
| Malaria VaccineAlso: PvRII/Matrix-Mblood stage Plasmodium vivax malaria vaccine | Biological | Malaria Vaccine |
| HBV vaccineHBV Vaccine | Biological | control |
Primary outcome
solicited local adverse event
Time frame: 7 days following each vaccination
occurrence of solicited local reactogenicity signs and symptoms
solicited systemic adverse event
Time frame: 7 days following each vaccination
occurrence of solicited systemic reactogenicity signs and symptoms
unsolicited adverse events
Time frame: 28 days following each vaccination
Occurrence of unsolicited adverse events
safety laboratory measures
Time frame: 28 days following each vaccination
Number of participants with abnormal laboratory test results
serious adverse events
Time frame: through study completion, an average of 1 year
Occurrence of serious adverse events during the whole study duration
feasibility of primary P. vivax blood-stage CHMI
Time frame: within 21 days following CHMI
successful infection (development of detectable persistent parasitaemia by thick blood film +/- clinical symptoms)
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 24 Mar 2026.
- Individual participant dataSharing planned: Yes. With participant's consent, suitably anonymised clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future.
Related trials for Plasmodium Vivax Infection
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Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
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Induced Blood-Stage Malaria in Healthy Malaria-Naive Adults to Assess the Safety and Infectivity of Plasmodium Vivax Challenge Agent and Evaluate Transmission in Mosquito Feeding Assays
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Safety and Immunogenicity of the Recombinant Malaria Vaccines in Healthy Adults Aged 18-50 Years
Malaria Vaccine
Not yet recruitingPhase 2
This is a Clinical Study to Assess Whether the Combination of SJ733 and Tafenoquine Will be a Safe and Rapidly Acting Anti-malarial for the Radical Cure of P. Vivax Malaria
Malaria, Malaria Vivax
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 Phase 2 study testing Malaria Vaccine and HBV vaccine in people with Plasmodium Vivax Infection and Malaria Vaccine, 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 10 inclusion and 34 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: opening soon, as of the sponsor's last update on 24 Mar 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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)2-3549170, Nickd@tropmedres.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
solicited local adverse event (time frame: 7 days following each vaccination). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2026.