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

This is an interventional prevention trial for Plasmodium Vivax Infection Read More

Inclusion Criteria:

1. Healthy Thai adults aged 20 to 55 years with a weight of at least 50 kg.
2. Graduated with a minimum of high school or equivalent
3. Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
4. Women only: Must practice continuous effective contraception for the duration of the study period until 3 months post-challenge.
5. Agreement to refrain from blood donation during the study and for 1 year after the initiation of antimalarial treatment.
6. Willing to be admitted to 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, and willing to reside in Bangkok and its vicinity for 2 months after malarial treatment initiation.
7. Able to read and write in Thai.
8. Provide written informed consent to participate in the trial
9. Answer all questions on the informed consent quiz correctly
10. Completed COVID-19 vaccination 3 doses of any WHO-approved vaccines

Exclusion Criteria:

1. Positive malaria qPCR OR malaria film
2. 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 severe cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition)
3. Presence of chronic disease or chronically use of medication
4. Prior receipt of an investigational vaccine is likely to impact the interpretation of the trial data or the P. vivax parasite as assessed by the Investigator.
5. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, history of splenectomy, recurrent, severe infections, and chronic infection
6. Immunosuppressant medication within the past 6 months preceding enrolment (D0) (inhaled and topical steroids are allowed)
7. History of allergic disease or reactions likely to be exacerbated by malaria infection
8. 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
9. Contraindications to the use of antimalarial treatment (e.g., chloroquine, atovaquone/proguanil, or dihydroartemisinin/piperaquine)
10. Use of medications known to have potentially clinically significant interaction with the antimalarial drug that will be used in this study (chloroquine, atovaquone/proguanil, or dihydroartemisinin/piperaquine)
11. 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
12. Family history of congenital QT prolongation or sudden death
13. Any clinical condition, including using medications known to prolong the QT interval or screening electrocardiogram (ECG), demonstrates a QTc interval ≥ 450 ms.
14. Suspected or known history of alcohol abuse or history of drug abuse.
15. Concurrently participating in another clinical study, at any time during the study period
16. Positive hepatitis B surface antigen or seropositive for hepatitis C virus, or HIV

17. Finding on safety laboratory values as defined below:

    • Abnormal ALT [upper normal range]
    • Abnormal serum creatinine [upper normal range]
    • Abnormalities corrected calcium and magnesium blood levels
18. Blood group Rhesus negative
19. Blood incompatibility to the inoculum
20. Positive for COVID-19
21. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
22. 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).
2. Current COVID-19 infection is defined as ongoing symptoms with a positive COVID-19 PCR swab test taken during the current illness or a positive COVID-19 PCR swab test within 14 days without symptoms. Vaccinations will be delayed by a minimum of 2 weeks from the date of the 1st positive COVID-19 PCR swab as long as symptoms are improving or resolved. It will be at the discretion of the Investigator to withdraw a participant if they develop severe COVID-19 disease.

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 subject must be withdrawn and followed until the resolution of the event, as with any adverse event:

1. Anaphylactic reaction following administration of the vaccine
2. Pregnancy

Exclusion criteria on the day of CHMI

The following constitute absolute contraindications to CHMI:

1. Acute disease, defined as a moderate or severe illness with or without fever
2. Current COVID-19 infection is defined as ongoing symptoms with a positive COVID-19 PCR swab test taken during the current illness or a positive COVID-19 PCR swab test within 14 days without symptoms.
3. Pregnancy
4. 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) -