Inoculation of infected blood cells to study Plasmodium vivax malaria

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

This study is testing if giving healthy Thai adults small doses of infected blood cells can help researchers learn more about malaria and find the best dose for future studies.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 20 Years to 55 Years
• Sex: All
• Sponsor: University of Oxford (other)
• Locations: 1 site (Bangkok)
• Trial ID: NCT05071079 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety and feasibility of controlled human malaria infection using cryopreserved infected erythrocytes in healthy Thai adults. A total of 48 volunteers will be inoculated with different doses of P. vivax infected blood cells to determine the optimal dose for future studies. Participants will undergo a thorough screening process and will be monitored closely in a hospital setting throughout the study duration, which spans approximately 13 months. The study will help establish a challenge model for future malaria research.

Who should consider this trial

Good fit: Ideal candidates are healthy Thai adults aged 20 to 55 years who are Duffy antigen positive.

Not a fit: Patients who are not Duffy antigen positive or those with underlying health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and treatment strategies for Plasmodium vivax malaria.

How similar studies have performed: Previous studies using controlled human malaria infection models have shown promise, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

The volunteer must meet all of the following criteria to be eligible for the study:

1. Healthy Thai adult aged 20 to 55 years with weight at least 50 kg.
2. Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
3. Women only: Must practice continuous effective contraception for the duration of study period until 3 months post-challenge.
4. COVID-19 vaccination at least two doses of COVID-19 vaccines approved by WHO.
5. Agreement to refrain from blood donation during the course of the study and for 1 year after the initiation of antimalarial treatment.
6. Willing to be admitted in the Hospital for Tropical Diseases for clinical monitoring, until antimalarial treatment is completed and their symptoms are settling.
7. Willing to take a curative antimalarial treatment following CHMI.
8. Willing to reside in Bangkok and its vicinity for 2 months after malarial treatment initiation.
9. Able to read and write in Thai.
10. Provide written informed consent to participate in the trial
11. Answer all questions on the informed consent quiz correctly
12. Educational level: has at least an undergraduate degree

Exclusion Criteria:

The volunteer must NOT enter the study if any of the following apply:

1. Positive malaria qPCR OR malaria film
2. 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)
3. Presence of chronic disease or chronically use of medication
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)
5. Use of immunoglobulins or blood products (e.g. blood transfusion) at any time in the 1 year preceding enrolment
6. Receipt of an investigational product, any vaccine in the 30 days preceding enrolment (D0), or planned receipt during the study period
7. 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.
8. Any confirmed, or suspected immunosuppressive, or immunodeficient state, including HIV infection, asplenia, history of splenectomy, recurrent, severe infections, and chronic infection
9. Immunosuppressant medication within the past 6 months preceding enrolment (D0) (inhaled and topical steroids are allowed)
10. History of allergic disease or reactions likely to be exacerbated by malaria infection
11. 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
12. Contraindications to the use of antimalarial treatment (e.g. chloroquine, atovaquone / proguanil or dihydroartemisinin/piperaquine)
13. 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)
14. Known existing positive family history in both 1st AND 2nd degree relatives \< 50 years old for cardiac disease
15. History of cardiac arrhythmia, including clinically relevant bradycardia
16. Family history of congenital QT prolongation or sudden death
17. Any clinical condition, including using medications, known to prolong the QT interval.
18. Screening electrocardiogram (ECG) demonstrates a QTc interval ≥ 450 ms.
19. Suspected or known or history of alcohol abuse
20. Suspected or known or history of drug abuse.
21. Concurrently participating in another clinical study, at any time during the study period
22. Haemoglobin \< 11 g/dL
23. Positive hepatitis B surface antigen or seropositive for hepatitis C virus
24. 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
25. Blood group Rhesus negative
26. Blood incompatibility to the inoculum
27. Positive for COVID-19 diagnosed by RT-PCR

Where this trial is running

Bangkok

• Faculty of Tropical Medicine — Bangkok, Thailand (RECRUITING)

Study contacts

• Principal investigator: Nicholas Day, MD — University of Oxford
• Study coordinator: Nicholas Day, MD

Conditions: Plasmodium Vivax Infection, controlled human malaria infection