Assessing safety and feasibility of malaria infection in healthy volunteers in Thailand

A Clinical Study to Assess the Feasibility of a Controlled Human Plasmodium Vivax Malaria Infection Model Through Sporozoite Infection in Thai Adults

This study is testing whether it's safe for healthy adults in Thailand to be intentionally infected with malaria to help researchers learn more about the disease and how the body responds to it.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 20 Years to 55 Years
• Sex: All
• Sponsor: University of Oxford (Academic / other)
• Locations: 1 site (Bangkok)
• Trial ID: NCT04083508 on ClinicalTrials.gov

What this trial studies

This study involves healthy Thai adults who will be intentionally infected with Plasmodium vivax malaria through bites from infected mosquitoes to evaluate the safety and feasibility of this controlled human malaria infection. Participants will undergo a thorough screening process and will be monitored closely for symptoms and parasitemia following the infection. The study aims to develop a bank of P. vivax-infected blood for future research and to gather data on the immune response to the infection. Participants will receive standard antimalarial treatment as per Thai guidelines after the challenge.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 20 to 55 years, with specific blood group and genetic criteria, residing in Bangkok.

Not a fit: Patients with underlying health conditions or those not meeting the strict eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of P. vivax malaria and improve treatment strategies for future patients.

How similar studies have performed: Previous studies involving controlled human malaria infections have shown promise, but this specific approach with P. vivax is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Healthy adult aged 20 to 55 years with weight more than 50 kg.
* Blood group O.
* Red blood cells positive for the Duffy antigen/chemokine receptor (DARC).
* CYP2D6 alleles consistent with normal metaboliser status
* Normal blood levels of Glucose-6-phosphate dehydrogenase (G6PDH) by the WHO definition.
* COVID-19 vaccination at least two doses of COVID-19 vaccine(s) approved by WHO.
* Agree to practice continuous effective contraception for the duration of study period until 3 months post-challenge.
* Agreement to refrain from blood donation during the course of the study and for 1 year after the end of their involvement in the study.
* Willing to take a curative antimalarial regimen following challenge.
* Willing to be admitted in the Hospital for Tropical Diseases for blood donation and clinical monitoring, until antimalarial treatment is completed and their symptoms are settling.
* Willing to reside in Bangkok for the duration of the study, until all antimalarial treatment has been completed.
* Reachable (24/7) by mobile phone during the period between challenge CHMI and completion of all antimalarial treatment.
* Able to read and write in Thai and able to answer ALL questions on the informed consent questionnaire correctly.
* Provided written informed consent to participate in the trial.
* Educational level: has at least an undergraduate degree.
* Cardiovascular risk assessment is low (less than 10% in the next 10 years according to the cardiovascular risk assessment from Thai NCD Division, DDC, MoPH (2016)

Exclusion Criteria:

* History of clinical malaria.
* Positive malaria PCR OR malaria film OR malaria serology (recent exposure)
* History of severe allergy to mosquito bite
* 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)
* Presence of chronic disease or chronically use of medication.
* Plan to travel outside of Bangkok within the period of challenge until 3 months after.
* 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).
* Use of immunoglobulins or blood products (e.g. blood transfusion) at any time in the 1 year preceding enrolment.
* Venipuncture unlikely to allow blood donation according to the protocol as determined by the investigator.
* Receipt of an investigational product or any vaccine in the 30 days preceding enrolment (D0), or planned receipt during the study period.
* 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.
* 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) (inhaled and topical steroids are allowed).
* History of allergic disease or reactions likely to be exacerbated by malaria infection.
* Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
* Contraindications to the use of antimalarial treatment (e.g. chloroquine or primaquine or atovaquone / proguanil, DHA piperaquine).
* Use of medications known to have a potentially clinically significant interaction with antimalarial drug that will be used in this study (chloroquine or primaquine or atovaquone / proguanil, DHA/ piperaquine).
* Use of medications known to cause prolongation of the QT interval as state in the section of prohibited drugs that may have effect on prolongation of the QT interval.
* 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 known to prolong the QT interval.
* History of cardiac arrhythmia, including clinically relevant bradycardia.
* Screening ECG demonstrates a QTc interval ≥ 450 ms
* Suspected or known or history of alcohol abuse
* Suspected or known or history of drug abuse.
* Concurrently participating in another clinical study, at any time during the study period.
* Haemoglobin \< 13 g/dL in male, \< 12g/dL in female (Thai Red Cross).
* Finding on safety laboratory values as defined below:
* AST \> 40 U/L for male, and \> 32 U/L for female (upper normal range), or
* ALT \> 41 U/L for male, and \> 33 U/L for female (upper normal range), or
* Total Bilirubin \> 1.2 mg/dL, (upper normal range), or
* Creatinine (Cr) \> 1.17 mg/dL for male, and \> 0.95 mg/dL for female (upper normal range), or
* Abnormalities corrected calcium and magnesium blood levels, or
* Fasting blood sugar (FBS) \> 100 mg/dL
* Thalassaemia disease or haemoglobinopathies.
* Positive for a blood borne or vector borne infectious disease (HIVI-II, HBV, HCV, Dengue, Zika, Chikungunya, Filariasis, JE, and malaria antigen, Anti HTLVI and Anti-HTLVII antibody, Syphilis test (TPHA)
* Positive for COVID-19 testing as 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