NCT05507970

First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of MMV367

A First-in-Human, Single-Centre, Single Ascending Dose, Multiple Dose and Pilot Food Effect Study to Assess the Safety, Tolerability and Pharmacokinetics of MMV367 in Healthy Participants

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: Medicines for Malaria Venture · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This three-part, first-in-human, healthy volunteer study aims to assess the safety and tolerability of the test medicine as well as how it is taken up by the body when given as single and multiple doses. The effect of food on the test medicine will also be investigated. In Part 1, up to 40 volunteers will be split into up to 5 groups and will receive single oral doses of the test medicine or dummy medicine (placebo), at different dose levels. In Part 2, up to 8 volunteers will receive one oral dose of the test medicine in the fed state and one oral dose in the fasted state. In Part 3, up to 24 volunteers will be split into up to 3 groups and will receive single oral daily doses of the test medicine or placebo for 3 consecutive days. Volunteers' blood and urine will be taken throughout the study for analysis of the test medicine and for their safety. In Part 1 and Part 3, volunteers will be discharged from the clinical unit 4 days after the final dose of the test medicine and will return to the clinical unit on two occasions for safety assessments to be performed. In Part 2, volunteers will be discharged from the clinical unit 4 days after the final dose of the test medicine and will return to the clinical unit on a single occasion for safety assessments to be performed. Volunteers are expected to be involved in this study for approximately 6 weeks for all study parts, from screening to the final return visit.

Detailed description

Part 1 will be a double-blinded, randomised, placebo-controlled, single ascending dose (SAD) study, which will comprise up to 5 fasted cohorts (Cohorts 1A to 1E; Cohort 1E will be optional), with 8 participants in each cohort. Participants will be randomly assigned to receive a single oral dose of either active IMP (investigational medicinal product) (6 participants) or placebo (2 participants) to assess its safety, tolerability and PK (pharmacokinetic) profile. Each participant will take part in one cohort. Cohort A dose is 100mg. Doses for cohorts B to E will be determined following a blinded interim review of the safety, tolerability and PK data after each cohort, prior to the dose decision for subsequent cohorts. Part 2 will be an open-label, randomised, balanced two-period crossover, food effect evaluation. It is planned to enrol 8 participants. In Period 1, participants will be randomised to 1 of 2 treatment sequences. If a participant is randomised to receive MMV367 in the fasted state in Period 1, they will receive MMV367 in the fed state in Period 2 and vice versa. The dose administered in Part 2 will be determined once predicted human therapeutic concentrations of MMV367 and a safe exposure window has been established in Part 1. Part 3 will be a double-blinded, randomised, placebo-controlled, multiple-dose study. A total of 8 participants per cohort (A-C) will receive once-daily doses of MMV367 (6 participants) or placebo (2 participants) for 3 days, in the fasted state, to assess safety, tolerability and PK profile of multiple dosing. Cohorts 3B and 3C are optional and may proceed after a review of the safety and PK data. The dose(s) administered in Part 3 will be determined after review of the data from Part 1. Parts 1 and 3 will follow a sentinel dosing design. For each of the three parts, participants will be screened within 28 days prior to first admission to the clinical unit on the morning of Day -1. Part 1: In each cohort, participants will be dosed on Day 1 and will remain resident in the clinical unit until discharge on Day 5. They will attend the clinical unit for a return visit on Day 7 and again on Day 15 for end of study assessments. Part 2: Participants will be dosed on Day 1 (Period 1 dose) and on Day 8 (Period 2 dose) and will remain resident in the clinical unit until discharge on Day 12. They will attend the clinical unit on Day 14 for end of study assessments. Based on emerging PK data from Part 1, the washout period between the Period 1 and Period 2 doses may be extended. Part 3: Participants will receive a single dose on Days 1, 2 and 3 and will remain resident in the clinical unit until discharge on Day 7. They will attend the clinical unit for a return visit on Day 9 and again on Day 17 for end of study assessments. For all parts, blood samples will be collected at regular intervals for PK analysis and safety from Day 1 to discharge from the study.

Conditions

• Malaria,Falciparum

Interventions

Type	Name	Description
DRUG	MMV367	Single dose dispersed in sterile water, fasted.
DRUG	Placebo	Single Dose dispersed in sterile water, fasted.
DRUG	MMV367 (Fed 440mg)	Single dose dispersed in sterile water with a high fat meal.
DRUG	MMV367	Single dose dispersed in sterile water, fasted, administered for 3 consecutive days.
DRUG	Placebo	Single dose dispersed in sterile water, fasted, administered for 3 consecutive days.
DRUG	MMV367 (Fasted 440mg)	Single dose dispersed in sterile water fasted.

Timeline

• Start date: 2022-07-29
• Primary completion: 2023-01-25
• Completion: 2023-01-25
• First posted: 2022-08-19
• Last updated: 2025-01-29
• Results posted: 2025-01-29

Locations

1 site across 1 country: United Kingdom