A Controlled Human Vivax Malaria Infection Study Through Inoculation of Infected Erythrocytes
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
University of Oxford
48 participants
May 23, 2022
INTERVENTIONAL
Conditions
Summary
The primary objectives of this study are to assess the safety and feasibility of blood-stage controlled human P. vivax malaria infection (CHMI) in healthy adult Thai volunteers through experimental injection of cryopreserved P. vivax infected erythrocytes, and to choose the optimal inoculation dose for future P. vivax CHMI studies. In this study, blood-stage CHMI will be conducted in 8 volunteers per inoculum stock who will each be infected with P. vivax by experimental injection with cryopreserved P. vivax infected erythrocytes, which were collected from the controlled human Plasmodium vivax malaria infection model through experimental sporozoite infection in Thai adults (NCT04083508) . There are currently 4 stocks of inocula from 6 volunteers in the NCT04083508 study, which have differing quantities and stages of parasites. The total number of volunteers of this study will be up to 48 (8 volunteers per inocula stock). The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases, and will be treated according to the Research Proposal. 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.
Eligibility
Inclusion Criteria13
- The volunteer must meet all of the following criteria to be eligible for the study:
- Healthy Thai adult aged 20 to 55 years with weight at least 50 kg.
- Red blood cells positive for the Duffy antigen/chemokine receptor (DARC)
- Women only: Must practice continuous effective contraception for the duration of study period until 3 months post-challenge.
- COVID-19 vaccination at least two doses of COVID-19 vaccines approved by WHO.
- Agreement to refrain from blood donation during the course of the study and for 1 year after the initiation of antimalarial treatment.
- Willing to be admitted in 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.
- 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
- Educational level: has at least an undergraduate degree
Exclusion Criteria32
- The volunteer must NOT enter the study if any of the following apply:
- Positive malaria qPCR OR malaria film
- 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
- 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
- Receipt of an investigational product, 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 as evidenced by positive beta-human chorionic gonadotropin (β-HCG) test, 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 a potentially clinically significant interaction with the antimalarial drug that will be used in this study (chloroquine, atovaquone / proguanil or dihydroartemisinin/piperaquine)
- Known existing positive family history in both 1st AND 2nd degree relatives < 50 years old for cardiac disease
- History of cardiac arrhythmia, including clinically relevant bradycardia
- Family history of congenital QT prolongation or sudden death
- Any clinical condition, including using medications, known to prolong the QT interval.
- Screening electrocardiogram (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 < 11 g/dL
- Positive hepatitis B surface antigen or seropositive for hepatitis C virus
- 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
- Blood group Rhesus negative
- Blood incompatibility to the inoculum
- Positive for COVID-19 diagnosed by RT-PCR
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Interventions
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with whole dose blood-stage inoculum (neat)
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:5 dilution blood-stage inoculum
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:10 dilution blood-stage inoculum
An inoculum of malaria parasitised red blood cells reconstituted in 0.9% normal saline, to a total volume of 5 mL; challenge with 1:20 dilution blood-stage inoculum
Locations(1)
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NCT05071079