Swiss BioQuant AG

This is an open-label, adaptive study using the P. falciparum induced blood stage malaria (IBSM) model to characterise the pharmacokinetic/pharmacodynamic (PK/PD) profile and safety of MMV367 (the IMP). Up to 18 participants will be enrolled in cohorts of up to 6 participants each. The study will proceed as follows for all participants:
Screening period of up to 28 days to recruit healthy adult participants.
Day 0: Intravenous inoculation with approximately 2,800 viable P. falciparum-infected red blood cells.
Days 1-3: Daily follow up via phone call or text message.
Days 4-7: Daily site visits for clinical evaluation and blood sampling to monitor malaria parasite numbers via quantitative polymerase chain reaction (qPCR).
Day 7 PM: Start of confinement within the clinical trial unit.
Day 8: Administration of a single oral dose of the IMP (MMV367). Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship.
Days 8-11: Regular clinical evaluation and blood sampling while confined to monitor malaria parasite numbers and measure MMV367 plasma concentration.
Day 11 AM: End of confinement within clinical trial unit.
Days 12-23: Outpatient follow-up for clinical evaluation and blood sampling.
Day 24: Initiation of compulsory definitive antimalarial treatment with Riamet® (artemether/lumefantrine) and/or other registered antimalarials if required. Treatment will be initiated earlier than Day 24 in the event of:
Insufficient parasite clearance following IMP dosing
Parasite regrowth following IMP dosing Characterising the pharmacokinetic/pharmacodynamic relationship of MMV367
Participant discontinuation/withdrawal,
Investigator's discretion in the interest of participant safety.
Day 27: End of study visit for final clinical evaluation and to ensure complete clearance of malaria parasites.

This three-part, first-in-human, healthy volunteer study aims to assess the safety and tolerability of the test medicine as well as how it is taken up by the body when given as single and multiple doses. The effect of food on the test medicine will also be investigated.
In Part 1, up to 40 volunteers will be split into up to 5 groups and will receive single oral doses of the test medicine or dummy medicine (placebo), at different dose levels.
In Part 2, up to 8 volunteers will receive one oral dose of the test medicine in the fed state and one oral dose in the fasted state.
In Part 3, up to 24 volunteers will be split into up to 3 groups and will receive single oral daily doses of the test medicine or placebo for 3 consecutive days.
Volunteers' blood and urine will be taken throughout the study for analysis of the test medicine and for their safety. In Part 1 and Part 3, volunteers will be discharged from the clinical unit 4 days after the final dose of the test medicine and will return to the clinical unit on two occasions for safety assessments to be performed. In Part 2, volunteers will be discharged from the clinical unit 4 days after the final dose of the test medicine and will return to the clinical unit on a single occasion for safety assessments to be performed. Volunteers are expected to be involved in this study for approximately 6 weeks for all study parts, from screening to the final return visit.

This is an open-label, adaptive study that will utilise the P. falciparum induced blood stage malaria (IBSM) model to characterise the pharmacokinetic/pharmacodynamic (PK/PD) profile of pyronaridine. Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. Following a screening period of up to 28 days, cohorts of up to 6 healthy participants will be enrolled. Each participant will be inoculated intravenously on Day 0 with P. falciparum infected erythrocytes. Participants will be followed up daily on Days 1 to 3, and will attend the clinical unit once on Days 4, 5, 6 and 7 for clinical evaluation and blood sampling. Participants will be admitted to the clinical trial unit on Day 8 for a single oral dose of pyronaridine.
Different doses of pyronaridine will be administered across and within cohorts. Participants will be randomised to a dose group on the day of dosing. The highest dose of pyronaridine administered will be no more than 720 mg; the lowest dose administered will be no less than 180 mg.
Each subsequent cohort will be composed of up to 3 dose groups. The Safety Data Review Team (SDRT) will review all available safety and tolerability data from the previous cohort/s prior to inoculation of the next cohort.
Participants will be confined in the clinical unit for at least 96 h (Days 8 - 12) to monitor the safety and tolerability of pyronaridine dosing. Upon discharge from the clinical unit participants will be monitored on an outpatient basis up to Day 50±2. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 47±2 or earlier.