A Controlled Human Vivax Malaria Infection Study Through Inoculation of Infected Erythrocytes

Launched by UNIVERSITY OF OXFORD · Oct 6, 2021

Keywords

ClinConnect Summary

This clinical trial is studying how safe and feasible it is to intentionally infect healthy adults with a type of malaria called Plasmodium vivax. The researchers want to find the best dose of the malaria-infected blood to use in future studies. Up to 48 healthy Thai volunteers aged 20 to 55, who weigh at least 50 kg and have a specific blood type, will receive an injection of this infected blood. The participants will be closely monitored in a hospital to ensure their safety and to manage any symptoms that may arise.

To be eligible for this trial, volunteers must meet certain criteria, such as being in good health, having received two doses of COVID-19 vaccine, and being willing to stay in the hospital for monitoring. Women must also agree to use effective contraception during the study. Participants can expect to receive treatment for malaria after the infection and will need to stay nearby for two months after starting treatment. This study is funded by the Wellcome Trust and aims to help improve our understanding of malaria infections and potential treatments.

Gender

ALL

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