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

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.

Conditions

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

Interventions

OTHER

P. falciparum IBSM infection

Induced Blood Stage Malaria from infected erythrocytes.

DRUG

MMV367 5mg

Single dose

DRUG

MMV367 10mg

Single dose

DRUG

MMV367 20mg

Single dose

DRUG

MMV367 90mg

Single dose

DRUG

MMV367 1500mg

Single dose

DRUG

MMV367 3mg

Single dose

Sponsors & Collaborators

• GlaxoSmithKline

  collaborator INDUSTRY

• Southern Star Research

  collaborator INDUSTRY

• ICON plc

  collaborator INDUSTRY

• QIMR Berghofer Medical Research Institute

  collaborator OTHER

• Queensland Paediatric Infectious Diseases (QPID) laboratory

  collaborator UNKNOWN

• Swiss BioQuant

  collaborator INDUSTRY

• Medicines for Malaria Venture

  lead OTHER

Principal Investigators

• Benoit Bestgen, PhD · MMV

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-08-01

Primary Completion

2023-10-30

Completion

2023-10-30

Countries

• Australia

Study Locations