NCT06558643

Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of MMV371 LAI in Healthy Participants

A First-in-Human, Single-Centre, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of a Single Intramuscular Injection of MMV371 Long-Acting Injection Formulation in Healthy Participants

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Medicines for Malaria Venture · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Accepted

Summary

This three-cohort, first-in-human, healthy participant study aims to assess the test medicine's safety and tolerability, including injection site reactions and how it is taken up by the body when given as a single dose. For Cohort 1, up to 8 participants will be randomly assigned to receive the starting dose of the test medicine or dummy medicine (placebo) as a single intramuscular injection. For Cohort 2, if the safety and tolerability results from Cohort 1 are satisfactory, up to 8 participants will be randomly assigned to receive double the starting dose of the test medicine or dummy medicine (placebo) as a single intramuscular injection. For Cohort 3, if the safety and tolerability results from Cohort 1 are satisfactory, up to 8 participants will be randomly assigned to receive double the Cohort 2 dose of the test medicine or dummy medicine (placebo) as a single intramuscular injection. Participants' blood and urine will be taken throughout the study for analysis of the test medicine and for their safety. When in the clinical unit, the injection site will be checked daily for reactions, and a diary will be provided on discharge for further recording. Participants will be discharged 6 days after dosing and return to the clinical unit an additional 9 times for for safety assessments to be performed. Participants are expected to be involved in this study for approximately 12 weeks for all study activities, from screening to the final return visit.

Detailed description

This is a single-centre, participant- and investigator-blind, randomised, placebo-controlled, single ascending dose (SAD) study to assess the safety, tolerability and PK of a single intra-muscular depot injection of MMV371 long-acting injection (LAI) formulation in healthy participants. It is planned to enrol 3 sequential cohorts of up to 8 healthy male participants and healthy non-pregnant, non-lactating female participants. In each cohort, participants will be randomised in a ratio of 6 active IMP to 2 placebo. All cohorts will follow a sentinel dosing design. On Day 1, two sentinel participants (sentinel group) will be randomly assigned to receive a single IM dose of either active investigational medicinal product (IMP) or placebo (1 participant each) to assess safety (with a focus on acute severe toxicity) and tolerability, including injection site reactions (ISRs). The sentinel group will be dosed concomitantly at least 48 h prior to the rest of the cohort (main group). The main group will comprise 6 participants randomly assigned to receive a single IM dose of either active IMP or placebo in a 5:1 ratio to assess safety and tolerability (including ISRs). An interim data review of the safety, tolerability (including ISRs), and PK data obtained up to Day 15 for each cohort will be conducted prior to the dose decision for the subsequent cohort(s). Should the data suggest that it is safe to proceed to the next dose group, progression to that group will be permitted. The starting dose will be 112 mg MMV371, and dose escalation between SAD cohorts will be a maximum of 2-fold. No dose selected will exceed 446 mg MMV371. * Cohort 1 will receive Regime A : MMV371 (112 mg (0.5 mL), or placebo. * Cohort 2 will receive Regime B: MMV371 (223 mg (1.0 mL), or placebo. * Cohort 3 will receive Regime C: MMV371 (446 mg (2.0 mL), or placebo. In each cohort, participants will be dosed on Day 1 and will remain residents in the clinical unit until discharge on Day 6. They will be required to return to the clinical unit on Days 8, 10, 12, 15, 18, 23, 29, and Week 8 for the assessments detailed in the schedule of assessments and Week 12 for the end-of-study assessment. For all parts, blood samples will be collected at regular intervals for PK analysis and safety from Day 1 to discharge from the study. Participants will also be trained to complete an Injection Site Reaction Diary(ISRD) whilst resident in the clinical unit. They will receive an ISRD at discharge on Day 6 and at each return visit until the EOS visit. The ISRD should be completed at home to document new, changing or re-appearing ISRs on non-visit days/weeks; changes at the injection site or the re-appearance of an ISR(s) should be recorded in the diary whenever they occur.

Conditions

• Malaria,Falciparum

Interventions

Type	Name	Description
DRUG	MMV371 LAI	Single intra-muscular dose
DRUG	Placebo for MMV371	Single intramuscular dose

Timeline

• Start date: 2024-08-27
• Primary completion: 2025-09-03
• Completion: 2025-09-03
• First posted: 2024-08-19
• Last updated: 2025-09-29

Locations

1 site across 1 country: United Kingdom