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 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.

This is a single-centre, open-label, Phase Ib study designed to assess if intravenous injection of approximately 3200 P. falciparum (NF54 strain) sporozoites can be safely administered to achieve blood-stage parasitaemia with a kinetics/PCR profile that will allow for the future characterisation of antimalarial blood-stage activity of new chemical entities in a relatively small number of participants during early drug development.
Healthy, malaria-naïve adults, aged 18-55 years, will be enrolled in a maximum of 2 cohorts. Enrolment into the cohorts will proceed sequentially, with two target levels of parasitaemia, i.e., 5000 parasites/mL blood in Cohort 1 and 10000 parasites/mL blood in Cohort 2.
(Based on observed levels of parasitaemia in Cohort 1, the target threshold for treatment in Cohort 2 was maintained at 5,000 p/mL (vs 10,000 p/mL in the protocol)).
The 3-day antimalarial therapy regimen will be further administered and monitored until parasite clearance. Safety and tolerability will be monitored during the whole study duration.