Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of MMV371 LAI in Healthy Participants
NCT Number: NCT06558643
Acronym: MV371 LAI FiH
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Malaria,Falciparum
Interventions: DRUG: MMV371 LAI|DRUG: Placebo for MMV371
Sponsor: Medicines for Malaria Venture
Collaborators: Quotient Sciences|The Doctors Laboratory
Sex: ALL
Age: ADULT
Enrollment: 24
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2025-03

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.

Primary Outcome Measures: Number of participants with adverse events (AEs) as assessed by the investigators., AEs (including SAEs),whether ascribed to study procedures or not, will be recorded from the time of providing written informed consent until the EOS visit/unscheduled follow-up visit. Participants will be asked to self-report any new, changing or re-appearing AEs in the 30 days after the Week 12 EOS visit.

Descriptive summaries of AE assessments by treatment will be provided., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with injection site reactions (ISRs) as assessed by DAIDS grading scale v2.1, At scheduled time points (0.5hr; 1hr; 2hr; 4hr; 6hr; 8hr; 12hr; 24hr; 48hr; 72hr; 96hr; 120hr; 168hr; 216hr; 264hr; 336hr; 408hr; 528hr; 672hr; 1344hr and 2016hr), following IMP administration, the injection site will be examined for presence of the following ISRs, which will be graded from Grade 1 (mild) to Grade 4 (potentially life-threatening), according to the DAIDS grading scale:

* Injection site pain/tenderness
* Injection site erythema/redness
* Injection site induration/swelling
* Injection site pruritis The presence and/or severity of erythema/redness and induration/swelling at the injection site will be assessed using the largest dimension.

Participants will be provided with an Injection Site Reaction Reaction Diary (ISRD) on discharge from the unit on Day 6 for recording new, changing, or reappearing ISRs on non-visit days/weeks.

Any clinically significant ISR will be reported as an AE as per the judgement of the investigator., Dosing (Day 1) up to 30 days after end of study (EOS) visit.|Number of participants that present with injection site nodules assessed and recorded using a four-point scale., At scheduled time points (0.5hr; 1hr; 2hr; 4hr; 6hr; 8hr; 12hr; 24hr; 48hr; 72hr; 96hr; 120hr;168hr; 216hr; 264hr; 336hr; 408hr; 528hr; 672hr; 1344hr and 2016hr), following IMP administration, the injection site will be examined for presence of nodules, which will be scored from 0 (no nodule) to 3 (Large nodule \>1cm in diameter).

Injection Site Nodule Examination Score Nodules 0 No nodule

1. Small nodule \<0.5 cm in diamete4
2. Medium size nodule 0.5 to 1 cm in diameter
3. Large nodule \>1 cm in diameter

Participants will receive an Injection Site Reaction Reaction Diary (ISRD) on discharge from the unit on Day 6 for recording new, changing, or reappearing nodules on non-visit days/weeks.

Any clinically significant ISR will be reported as an AE as per the investigator's judgement., Dosing (Day 1) up to 30 days after end of study (EOS) visit.|Number of participants with abnormal findings during targeted Physical examination and/or Adverse Events related to treatment:, During the targeted (symptom-driven) physical examination (216hr; 672hr; 1344hr and 2016hr), following IMP administration, a physician will assess the participant; if the participant reports feeling unwell or has ongoing AEs, the physician will examine the appropriate body system(s) if required.

Examination of lymph nodes (mandibular, axillar and inguinal) for changes such as swelling and hardening (induration) will be conducted.

Descriptive summaries of physical assessments by treatment will be provided., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with abnormal safety blood results and/or Adverse Events related to treatment)., Safety blood samples collected at time points (Screening, admission; pre-dose; 4hr; 48hr; 216hr; 408hr; 672hr; 1344hr and 2016hr) are assessed for lab values for (haematology, coagulation (only pre-dose; 4hr; 408hr), biochemistry and urinalysis) that move out of the normal range will be noted and assessed for clinical significance. Any clinically significant abnormality, including changes from baseline, must be reported as an AE., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with abnormal electrocardiograms (ECGs) and/or Adverse Events related to treatment)., Triplicate ECGs are collected at the following time points (Screening, pre-dose; 4hr; 48hr; 216hr; 408hr; 672hr; 1344hr and 2016hr). The mean value for the triplicate ECGs (supine) will be reviewed for safety assessments. Any clinically significant abnormality, including changes from baseline, will be reported as an AE.

Absolute QTcF prolongation

* QTcF \>450 msec
* QTcF \>480 msec
* QTcF \>500 msec Change from baseline in QTcF
* QTcF increases from baseline \>30 msec
* QTcF increases from baseline \>60 msec, Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with abnormal vital signs and/or Adverse Events related to treatment: Blood pressure, Blood pressure is measured in millimetres of mercury (mmHg), at the following time points (Screening, pre-dose; 4hr; 48hr; 216hr; 408hr; 672hr; 1344hr and 2016hr) with the participant supine for a minimum of 5 minutes.

Any clinically significant abnormality, including changes from baseline, must be reported as an AE., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with abnormal vital signs and/or Adverse Events related to treatment: Heart rate., Heart rate is measured in beats per minute (bpm), at the following time points (Screening, pre-dose; 4hr; 48hr; 216hr; 408hr; 672hr; 1344hr and 2016hr) with the participant supine for a minimum of 5 minutes.

Any clinically significant abnormality, including changes from baseline, must be reported as an AE., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with abnormal vital signs and/or Adverse Events related to treatment:Respiration Rate, Respiration rate is measured in breaths per minute at the following time points (Screening, pre-dose; 4hr; 48hr; 216hr; 408hr; 672hr; 1344hr and 2016hr) with the participant supine for a minimum of 5 minutes.

Any clinically significant abnormality, including changes from baseline, must be reported as an AE., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Number of participants with abnormal vital signs and/or Adverse Events related to treatment: Body temperature., Body temperature is measured in degrees centigrade (°C), at the following time points (Screening, pre-dose; 4hr; 48hr; 216hr; 408hr; 672hr; 1344hr and 2016hr) with the participant supine for a minimum of 5 minutes.

Any clinically significant abnormality, including changes from baseline, must be reported as an AE., Screening/Day-28 up to 30 days after end of study (EOS) visit.|Participants' Weight in kilograms (kg), Weight is measured at Screening and Admission and will be combined with Height in centimetres (cm) to report BMI in kg/m\^2, Screening and Admission|Participants' Height in centimetres (cm), Weight is measured at Screening and Admission and will be combined with Height in centimetres (cm) to report BMI in kg/m\^2, Screening