Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 1:22 AM
Ignite Modification Date:
2025-12-25 @ 1:22 AM
NCT ID:
NCT05287893
Brief Summary:
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.
Detailed Description:
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 approximately 2,800 viable P. falciparum infected erythrocytes. Participants will be followed up daily via phone call or text message on Days 1 to 3 post-inoculation to solicit any adverse events. Participants will attend the clinical unit once on Days 4, 5, 6 and 7 for clinical evaluation and blood sampling to monitor the progression of parasitaemia, using quantitative polymerase chain reaction (qPCR) targeting the gene encoding 18S rRNA (referred to hereafter as malaria 18S qPCR). Participants will have a nasopharyngeal aspirate (NPA) for SARS-CoV-2 on Day 6 am in the event that there is community transmission in South East Queensland of SARS-CoV-2. Participants will also have blood collected on Day 7 am to monitor haematology and biochemistry. Participants will be admitted to the clinical trial unit on Day 8 for dosing with the investigational medicinal product (IMP; pyronaridine) when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Pyronaridine will be administered as a single oral dose. Different doses of pyronaridine will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Each cohort will comprise up to three dose groups, with participants 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. The proposed dosing regimen for the Cohort 1, assuming six participants are enrolled, is as below. If less than six participants are enrolled the Safety Data Review Team (SDRT) will meet between Day 0 and Day 8, to decide on the dose/s to be administered.
Dose group
1A (n=2) 360 mg
1B (n=2) 540 mg
1C (n=2) 720 mg
Each subsequent cohort will be composed of up to 3 dose groups. If more than one dose is tested in a given cohort, subjects will be randomised after inoculation day (Day 0) but prior to Day 8. The dose/s administered to Cohort 2 and Cohort 3 will be selected based on PK/PD and safety data from the preceding cohort/s. The SDRT will review all available safety and tolerability data and PK/PD analysis outcomes from the previous cohort/s prior to inoculation of the next cohort. The study will conclude when sufficient data have been obtained to define the PK/PD parameters for pyronaridine (the primary endpoint).
A maximum sample size of 18 participants administered pyronaridine is expected to be sufficient to achieve the primary endpoint.
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 and to ensure adequate clinical response against P. falciparum. During confinement, regular safety assessments will be performed and blood will be collected to monitor parasite clearance and pyronaridine concentration. If participants are clinically well at the end of the confinement period, they will be discharged and 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.
Study:
NCT05287893
Study Brief:
Protocol Section:
NCT05287893