Phase 1b MMV367 PK/PD and Safety in Healthy Adult Volunteers Experimentally Infected With Blood Stage P. Falciparum

Inflammation Clinical Trial

Official title: An Open Label Phase 1b Study to Characterise the Pharmacokinetic/Pharmacodynamic Relationship and Safety of MMV367 in Healthy Adult Participants Experimentally Infected With Blood Stage Plasmodium Falciparum

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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 erythrocytes.

• 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 parasitaemia 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 parasitaemia 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 (parasitaemia not reduced ≥10-fold by Day 10 compared with peak parasitaemia on Day 8).

• Parasite regrowth following IMP dosing (initial parasite clearance is followed by asexual parasite regrowth above 5000 parasites/mL).

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 parasitaemia (at least one negative qPCR result required). ;

Related Conditions & MeSH terms

• Anti-Infective Agents
• Antimalarials
• Communicable Diseases
• Infections
• Inflammation
• Malaria
• Malaria, Falciparum
• Malaria,Falciparum
• Parasitemia
• Parasitic Diseases
• Pathologic Processes
• Protozoan Infections
• Systemic Inflammatory Response Syndrome
• Vector Borne Diseases

• NCT number: NCT05979207
• Study type: Interventional
• Source: Medicines for Malaria Venture
• Status: Completed
• Phase: Phase 1
• Start date: August 1, 2023
• Completion date: October 30, 2023