A pilot study to characterize the safety and infectivity of a Plasmodium knowlesi parasite bank in healthy volunteers

Challenge Agent The malaria challenge agent, containing the relevant number of viable Plasmodium knowlesi YH1-HS parasite-infected erythrocytes in a volume of 2 mL, will be administrated intravenously on Day 0. The first cohort will receive approximately 2,800 viable parasites. Subsequent cohorts may receive a higher dose of approximately 28,000 viable parasites or 280,000 viable parasites in accordance with the dose escalation criteria. The actual number of parasites inoculated will take into account the loss of viability resulting from cryopreservation, storage and thawing. If a dose increase is required between cohort 1 and cohort 2, the dose will increase from 2800 parasites in cohort 1 to 28,000 parasites in cohort 2. If a further dose increase is required, the dose will increase from 28,000 parasites to 280,000 parasites in the subsequent cohort. The maximum dose will be 280,000 parasites. Participants will report to the clinical unit on inoculation day after fasting for greater than or equal to 8 hours and undergo intravenous cannulation. The inoculum will be injected, and the cannula flushed with clinical grade saline. The cannula will then be removed. An extra syringe will be prepared to quantify the parasite count of the challenge agent by Polymerase Chain Reaction (PCR). The duration of the inoculation is less than 1 minute. Definitive antimalarial medications Compulsory definitive antimalarial treatment for all participants will be initiated when parasitaemia is greater than or equal to 10,000 parasites/mL, or on Day 21 (whichever occurs first). Earlier treatment will be initiated if a participant experiences a serious adverse event (SAE), or at the Investigator’s discretion in the interest of participant safety. Riamet® tablets will be administered as six oral doses of four tablets (total course of 24 tablets equivalent to 480 mg artemether and 2.88 g lumefantrine). The second dose of four tablets will be administered 8±1 h after the first dose. The remaining doses will be administered twice daily (morning and evening). Malarone® will be utilised as a backup medication to Riamet® in the event of allergy or contraindication to Riamet®. A treatment course consists of four tablets administered daily for three days (total course of 12 tablets equivalent to 3 g atovaquone and 1.2 g proguanil hydrochloride). Malarone is adminstered daily for 3 days. The 2nd and 3rd doses will be taken approximately 24 and 48 hours after the first dose. The first dose of Riamet and Malarone will be supervised. The subsequent doses may be taken at home. Participants will receive a phone call or text message from the clinical trial unit staff to ensure compliance. Intravenous artesunate may be administered in the event a participant vomits or cannot tolerate oral drugs. In this case, the participant will be admitted to hospital for treatment. Artesunate will be administered as 2.4 mg/kg IV bolus on admission, with repeat dosing at 12 hours and 24 hours, then once daily until oral therapy is possible.