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

NCT05979207 | Completed Phase 1 Results

• 1 other identifier: MMV_MMV367_22_01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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

Keywords

Malaria; Parasitaemia; Malaria Recrudescence; Malaria, Falciparum

Outcome Measures

Primary Outcomes (5)

• Emax

  Maximum effect of drug (maximum parasite killing rate). Emax used in the PK/PD model comes from the mean viable parasite elimination half-life of cohort 1 as estimated in the parasite viability report as Emax was not clearly observed in the cohort 2 parasitemia profiles.

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

• EC50

  Half Maximal Effective Concentration PK/PD dataset contains the individual information from all arms including date and time of inoculum administration, MMV367 dose; MMV367 plasma PK concentrations; total parasitemia counts by 18S qPCR; gametocytemia counts by pfs25, pfMGET and pfSBP-1 if relevant; and typical covariates such as age, body weight, height, sex and race, to build the model and derive outcome results.

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

• MIC

  MIC is defined as the concentration when drug killing equals the parasite growth, i.e., the time at which the minimum parasite concentration is observed. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan.

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

• MPC90

  MPC90 is defined as the concentration at which the clearance effect is at 90% of the maximum. Calculated using the combined data from all doses/arms/groups in both period 1 and 2, as prespecified in section 10 of the Statistical Analysis Plan. PK/PD dataset contains the individual information from all arms including date and time of inoculum administration, MMV367 dose; MMV367 plasma PK concentrations; total parasitemia counts by 18S qPCR; gametocytemia counts by pfs25, pfMGET and pfSBP-1 if relevant; and typical covariates such as age, body weight, height, sex and race, to build the model and derive outcome results.

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

• Parasite Killing Achieved Within 48 Hours, PRR48

  PRR48 is given as the reduction of values on log10 transformed scale. Only MMV\_MMV367\_22\_01 data was used. PRR48 provides an estimate of the efficacy of an anti-malarial treatment. It is the ratio of parasite density over a 48-hour period, estimated using the slope of the optimal fit of the log-linear relationship of parasitemia decay. Optimal fit is derived using geometric mean parasitemia data (i.e. 18S qPCR measuring all blood stage malaria parasites). The optimal fit of the log-linear parasitemia decay by time relationship is determined using left and right censoring to systematically remove potential lag and tail phases of parasitemia decay. PRR48 was calculated for each participant using daily PCR data. If the model fit was adequate (overall model p-value\<0.001), the slope and corresponding SE from the log-linear regression was used to calculate overall dose-specific PRR48. Participants without adequate model fits were excluded from all dose-specific PRR48 calculations.

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

Study Arms (6)

MMV367 3mg

EXPERIMENTAL

IBSM challenge and MMV367 Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes. Day 8 participants will be dosed with MMV367 when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and MMV367 concentration. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 24, or earlier.

Drug: MMV367 3mg; Other: P. falciparum IBSM infection

MMV367 5mg

EXPERIMENTAL

IBSM challenge and MMV367 Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes. Day 8 participants will be dosed with MMV367 when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and MMV367 concentration. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 24, or earlier.

Other: P. falciparum IBSM infection; Drug: MMV367 5mg

MMV367 10mg

EXPERIMENTAL

IBSM challenge and MMV367 Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes. Day 8 participants will be dosed with MMV367 when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and MMV367 concentration. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 24, or earlier.

Other: P. falciparum IBSM infection; Drug: MMV367 10mg

MMV367 20mg

EXPERIMENTAL

IBSM challenge and MMV367 Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes. Day 8 participants will be dosed with MMV367 when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and MMV367 concentration. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 24, or earlier.

Other: P. falciparum IBSM infection; Drug: MMV367 20mg

MMV367 90mg

EXPERIMENTAL

IBSM challenge and MMV367 Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes. Day 8 participants will be dosed with MMV367 when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and MMV367 concentration. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 24, or earlier.

Other: P. falciparum IBSM infection; Drug: MMV367 90mg

MMV367 1500mg

EXPERIMENTAL

IBSM challenge and MMV367 Up to 18 healthy, malaria naïve adult participants are planned to be enrolled into this study, in cohorts of up to six participants each. on Day 0 participants will be inoculated intravenously with approximately 2,800 viable P. falciparum-infected erythrocytes. Day 8 participants will be dosed with MMV367 when parasitaemia for the majority of participants is expected to be above 5,000 parasites/mL. Different doses of MMV367 will be administered across and within cohorts in order to effectively characterise the PK/PD relationship. Regular safety assessments will be performed and blood will be collected to monitor parasite clearance and MMV367 concentration. Participants will receive compulsory antimalarial rescue treatment with Riamet® (artemether/lumefantrine) on Day 24, or earlier.

Other: P. falciparum IBSM infection; Drug: MMV367 1500mg

Interventions

MMV367 3mg DRUG

Single dose

MMV367 3mg

P. falciparum IBSM infection OTHER

Induced Blood Stage Malaria from infected erythrocytes.

MMV367 10mg; MMV367 1500mg; MMV367 20mg; MMV367 3mg; MMV367 5mg; MMV367 90mg

MMV367 5mg DRUG

Single dose

MMV367 5mg

MMV367 10mg DRUG

Single dose

MMV367 10mg

MMV367 20mg DRUG

Single dose

MMV367 20mg

MMV367 90mg DRUG

Single dose

MMV367 90mg

MMV367 1500mg DRUG

Single dose

MMV367 1500mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18 to 55 years inclusive who will be contactable and available for the duration of the trial and up to two weeks following the EOS visit.
• \. Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive). BMI is an estimate of body weight adjusted for height. It is calculated by dividing the weight in kilograms by the square of the height in metres.
• \. Completion of the written informed consent process prior to undertaking any trial-related procedure. 4. Must be willing and able to communicate and participate in the whole trial. 5. Agreement to adhere to Lifestyle Considerations (Section 5.3) throughout the trial duration.
• \. Must be able to provide contact details of a support person (responsible adult) who is aware of the participant's participation in the study and is available to provide assistance if required (for example with contacting the participant in the event that study staff are unable to, or with transporting the participant to and from the study site if required).
• Vital signs and ECG parameters 7. Vital signs at screening (measured after 5 min in the supine position):
• Systolic blood pressure (SBP): 90-140 mmHg,
• Diastolic blood pressure (DBP): 40-90 mmHg,
• \. At Screening and pre-inoculation with the malaria challenge agent (Day 0), normal standard mean of triplicate 12-lead electrocardiogram (ECG) parameters after 5 minutes resting in supine position:
• QTcF: ≤450 msec (males) or ≤470 msec (females),
• QRS: 50-120 msec,
• PR interval: ≤ 210 msec,
• Normal ECG tracing unless the Principal Investigator or delegate considers an ECG tracing abnormality to be not clinically relevant.
• Contraception 9. Women of childbearing potential (WOCBP) who anticipate being sexually active with a male during the trial must agree to use a highly effective method of birth control (see below) combined with a barrier contraceptive from the screening visit until 34 days after the last dose of MMV367 (covering a full menstrual cycle of 30 days starting after 5 half-lives of last dose of MMV367) and have a negative urine pregnancy test result prior to inoculation with the malaria challenge agent on Day 0.
• Highly effective birth control methods include: combined (oestrogen and progestogen containing) oral/intravaginal/transdermal/implantable hormonal contraception associated with inhibition of ovulation, progestogen-only oral/injectable/implantable hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, or sexual abstinence or same sex relationship.
• Female participants who are abstinent (from penile-vaginal intercourse) must agree to start a double method if they start a sexual relationship with a male during the study. Female participants must not be planning in vitro fertilisation within the required contraception period.

You may not qualify if:

• Medical history
• 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.
• 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.
• A score of 20 or more on the Beck Depression Inventory-II (BDI-II) and/or a response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation).
• \- The BDI-II will be used as a validated tool for the assessment of depression at screening. Participants that meet criterion 8 will be referred to a general practitioner or medical specialist as appropriate. Participants with a BDI-II score of 17 to 19 may be enrolled at the discretion of the Investigator if they do not have a history of the psychiatric conditions mentioned in criterion 6 and their mental state is not considered to pose additional risk to the health of the participant during the trial or to the execution of the trial and interpretation of the data gathered.
• History of splenectomy.
• Symptomatic postural hypotension at screening (confirmed on two consecutive readings), irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease of SBP of ≥20 mmHg after 3 min standing and/or a decrease of DBP of ≥10 mmHg after 3 min standing. This 3 min standing period will commence after the volunteer has rested for 5 min in the supine position.
• Cardiac/QT risk:
• Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.
• History of symptomatic cardiac arrhythmias or of clinically relevant bradycardia.
• Evidence of increased cardiovascular disease risk (defined as \>10%, 5-year risk for those greater than 35 years of age, as determined by the Australian Absolute Cardiovascular Disease Risk Calculator \[http://www.cvdcheck.org.au/\]). Risk factors include sex, age, systolic blood pressure (mm/Hg), smoking status, total and HDL cholesterol (mmol/L), and reported diabetes status.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• GlaxoSmithKline: collaborator
• Southern Star Research: collaborator
• ICON plc: collaborator
• QIMR Berghofer Medical Research Institute: collaborator
• Queensland Paediatric Infectious Diseases (QPID) laboratory: collaborator
• Swiss BioQuant: collaborator

Study Sites (2)

South Bank

Brisbane, Queensland, 4101, Australia

Location

USC Clinical Trials, Morayfield

Brisbane, Queensland, 4506, Australia

Location

MeSH Terms

Conditions

Infections; Vector Borne Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Malaria; Malaria, Falciparum; Parasitemia; Parasitic Diseases; Protozoan Infections

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Shock; Mosquito-Borne Diseases; Sepsis

Results Point of Contact

• Title: Director, Program Leadership and Strategy
• Organization: Medicines for Malaria Venture

info@mmv.org

+41 22 555 03 00

Study Officials

• Benoit Bestgen, PhD

  MMV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: MMV367 will be administered as a single oral dose, with different doses to be tested across and within cohorts. The highest dose of MMV367 administered in this study will be no more than 1500 mg, to determine the maximum parasite killing rate of MMV367. Doses to be tested in Cohort 1 will be 20mg, 90mg and 1500mg. Parasite regrowth following initial parasite clearance is required to effectively characterise PK/PD parameters such as the half maximum effective concentration of MMV367.The Safety Data Review Team will review all safety, PK, and PD data. Doses to be tested in Cohort 2 will be informed by the results obtained in Cohort 1, and will be selected to refine the PK/PD parameter estimates. The SDRT will meet following the completion of Cohort 2 to review all safety, PK, and PD data. If the SDRT deems sufficient data has been obtained to achieve the primary endpoint, a third cohort of participants will not be enrolled.

Study Record Dates

• First Submitted: July 30, 2023
• First Posted: August 7, 2023
• Study Start: August 1, 2023
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2023
• Last Updated: December 10, 2025
• Results First Posted: December 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)