CompletedPhase 1

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

Australia12 participantsStarted 2023-08-01

Plain-language 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.

Who can participate

Age range18 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Exclusion criteria

✕. Known hypersensitivity to artesunate or other artemisinin derivatives, lumefantrine, proguanil/atovaquone, primaquine, or 4-aminoquinolines.
✕. Any history of anaphylaxis or other severe allergic reactions, or other food or drug allergy that the Investigator considers may impact on participant safety.
✕. History of convulsion (including drug or vaccine-induced episodes). A medical history of febrile convulsion during childhood (\< 5 years) is not an exclusion criterion.
✕. Presence of current or suspected uncontrolled chronic diseases that may impact participant safety or interpretation of clinical trial results, such as (but not limited to) cardiac or autoimmune disease, diabetes, progressive neurological disease, severe malnutrition, hepatic or renal disease, epilepsy, or asthma.
✕. History of malignancy of any organ system (other than localised basal or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within five years of screening, regardless of whether there is no evidence of local recurrence or metastases.
✕. Individuals with history of schizophrenia, bipolar disorder psychoses, attempted or planned suicide, or any other severe (disabling) chronic psychiatric diagnosis including generalised anxiety disorder.
✕. History of an episode of depression lasting more than 6 months that required pharmacological therapy and/or psychotherapy within the last 2 years.

What they're measuring

Emax

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

EC50

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

MIC

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

MPC90

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

Parasite Killing Achieved Within 48 Hours, PRR48

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

Trial details

NCT IDNCT05979207

SponsorMedicines for Malaria Venture

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-10-30

Results submitted2024-09-25

View on ClinicalTrials.gov More Infections trials

Plain-language summary

Who can participate

Age range18 Years – 55 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Exclusion criteria

✕. Known hypersensitivity to artesunate or other artemisinin derivatives, lumefantrine, proguanil/atovaquone, primaquine, or 4-aminoquinolines.
✕. Any history of anaphylaxis or other severe allergic reactions, or other food or drug allergy that the Investigator considers may impact on participant safety.
✕. History of convulsion (including drug or vaccine-induced episodes). A medical history of febrile convulsion during childhood (\< 5 years) is not an exclusion criterion.
✕. Presence of current or suspected uncontrolled chronic diseases that may impact participant safety or interpretation of clinical trial results, such as (but not limited to) cardiac or autoimmune disease, diabetes, progressive neurological disease, severe malnutrition, hepatic or renal disease, epilepsy, or asthma.
✕. History of malignancy of any organ system (other than localised basal or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within five years of screening, regardless of whether there is no evidence of local recurrence or metastases.
✕. Individuals with history of schizophrenia, bipolar disorder psychoses, attempted or planned suicide, or any other severe (disabling) chronic psychiatric diagnosis including generalised anxiety disorder.
✕. History of an episode of depression lasting more than 6 months that required pharmacological therapy and/or psychotherapy within the last 2 years.

What they're measuring

Emax

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

EC50

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

MIC

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

MPC90

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)

Parasite Killing Achieved Within 48 Hours, PRR48

Timeframe: Day 8 (IMP dosing) until Day 27 (End of Study)