A Safety, Immunogenicity and Efficacy Study of PvRII/Matrix-M in Healthy Thai Adults Living in Thailand ( MIST3 )

NCT05380388 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: MAL22004
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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 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

Conditions

Plasmodium Vivax Infection; Malaria Vaccine

Outcome Measures

Primary Outcomes (6)

• solicited local adverse event

  occurrence of solicited local reactogenicity signs and symptoms

  7 days following each vaccination

• solicited systemic adverse event

  occurrence of solicited systemic reactogenicity signs and symptoms

  7 days following each vaccination

• unsolicited adverse events

  Occurrence of unsolicited adverse events

  28 days following each vaccination

• safety laboratory measures

  Number of participants with abnormal laboratory test results

  28 days following each vaccination

• serious adverse events

  Occurrence of serious adverse events during the whole study duration

  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)

  within 21 days following CHMI

Study Arms (2)

Malaria Vaccine

EXPERIMENTAL

PvRII/Matrix-M month 0, month 1, month 6

Biological: Malaria Vaccine

control

OTHER

HBV vaccine month 0, month 1, month 6

Biological: HBV vaccine

Interventions

Malaria Vaccine BIOLOGICAL

blood stage Plasmodium vivax malaria vaccine

Also known as: PvRII/Matrix-M

Malaria Vaccine

HBV vaccine BIOLOGICAL

HBV Vaccine

control

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol University: collaborator

Study Sites (1)

Faculty of Tropical Medicine

Bangkok, 10400, Thailand

Location

MeSH Terms

Interventions

Malaria Vaccines; Matrix-M

Intervention Hierarchy (Ancestors)

Protozoan Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Nicholas Day, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Day, MD

CONTACT

+66-(0)2-3549170; Nickd@tropmedres.ac

Jetsumon Sattabongkot Prachumsri, Ph. D

CONTACT

+66-(0)2-3549100; jetsumon.pra@mahidol.ac.th

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-blinded placebo
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized placebo-controlled trial

Study Record Dates

• First Submitted: April 13, 2022
• First Posted: May 18, 2022
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)