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

NCT06558643 | Completed Phase 1

• 1 other identifier: MMV_MMV371_23_01_FIH
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This four-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. For Cohort 4, if the safety and tolerability results from Cohort 3 are satisfactory, up to 8 participants will be randomly assigned to receive a single dose 1.5 higher than Cohort 3 dose, administered as two IM injections, each at different anatomical locations (one in each deltoid muscle). 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 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.

Conditions

Malaria,Falciparum

Keywords

Malaria; First in Human; Healthy Volunteers; Long Acting Injection

Outcome Measures

Primary Outcomes (1)

• 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. Only the drug related treatment emergent adverse events will be reported.

  Screening/Day-28 up to 30 days after end of study (EOS) visit.

Study Arms (4)

Cohort 1 Single Ascending Dose Regime A

EXPERIMENTAL

MMV371 Long-acting injection (LAI) 112mg (0.5 ml) or Placebo for MMV371 Long-acting injection(0.5 ml)

Drug: MMV371 LAI; Drug: Placebo for MMV371

Cohort 2 Single Ascending Dose Regime B

EXPERIMENTAL

MMV371 Long-acting injection (LAI) 223mg (1.0 ml) or Placebo for MMV371 Long-acting injection (1.0 ml)

Drug: MMV371 LAI; Drug: Placebo for MMV371

Cohort 3 Single Ascending Dose Regime C

EXPERIMENTAL

MMV371 Long-acting injection (LAI) 446mg (2.0 ml) or Placebo for MMV371 Long-acting injection (2.0 ml)

Drug: MMV371 LAI; Drug: Placebo for MMV371

Cohort 4 Single Ascending Dose Regime D

EXPERIMENTAL

MMV371 Long-acting injection (LAI) 669mg (3.0 ml) or Placebo for MMV371 Long-acting injection (3.0 ml)

Drug: MMV371 LAI; Drug: Placebo for MMV371

Interventions

MMV371 LAI DRUG

Single intra-muscular dose

Cohort 1 Single Ascending Dose Regime A; Cohort 2 Single Ascending Dose Regime B; Cohort 3 Single Ascending Dose Regime C; Cohort 4 Single Ascending Dose Regime D

Placebo for MMV371 DRUG

Single intramuscular dose

Cohort 1 Single Ascending Dose Regime A; Cohort 2 Single Ascending Dose Regime B; Cohort 3 Single Ascending Dose Regime C; Cohort 4 Single Ascending Dose Regime D

Eligibility Criteria

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

You may qualify if:

• Must provide written informed consent
• Must be willing and able to communicate and participate in the whole study Aged 18 to 64 years inclusive at the time of signing informed consent
• \. Must agree to adhere to the contraception requirements defined in Section 9.4 of the Protocol 5. Healthy males or non-pregnant, non-lactating healthy females, determined by normal physical examination, safety bloods, urinalysis, ECG and vital sign assessments 6. Body mass index (BMI) of 19.0 to 32.0 kg/m2 as measured at screening 7. Weight ≥50 kg for males and ≥45 kg for females at screening

You may not qualify if:

• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients, Wellvone®/Mepron® and/or Malarone®
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
• History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
• Blood pressure (BP; supine) at screening or pre-dose outside the range of 90 to 140 mmHg systolic BP in participants ≤45 years, 90 to 150 mmHg SBP in participants \>45 years or 50 to 90 mmHg diastolic BP; and pulse rate outside the range of 45 to 100 bpm, unless deemed not clinically significant by the investigator
• History or presence of known structural cardiac abnormalities, family history of long QT syndrome, cardiac syncope or recurrent, idiopathic syncope, exercise related clinically significant cardiac events. Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of QT interval changes
• Presence of sinus node dysfunction, clinically significant PR interval prolongation (\>220 msec), intermittent second- or third-degree atrioventricular block, complete bundle branch block, sustained cardiac arrhythmias including (but not limited to) atrial fibrillation or supraventricular tachycardia; any symptomatic arrhythmia with the exception of isolated extra systoles, abnormal T wave morphology which may impact on the QT/QTc assessment, or QTcF \>450 msec.
• Participants with a history of cholecystectomy or gall stones.
• Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
• Participants with tattoos or scars or other significant dermatological conditions overlying the deltoid region which may interfere with injection site assessments, as determined by the investigator or delegate at screening.
• Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1). Participants with Gilbert's Syndrome are not allowed
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results.
• Transaminases (ALT or AST) \>ULN
• Females who are pregnant or lactating (all female participants must have a negative highly sensitive serum pregnancy test at screening and a negative urine pregnancy test at admission).
• Participants who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer
• Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Quotient Sciences: collaborator
• The Doctors Laboratory Ltd: collaborator

Study Sites (1)

Quotient Sciences

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Nand Singh, MD DPM FFPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Appearance matching of the placebo is not possible; therefore, non-blinded dosing teams will be used to preserve the study blind. IMP labels will state MMV371 or placebo and use a common expiry date. IMP accountability logs will be maintained by unblinding the randomisation schedule and disclosure envelopes will be generated by an unblinded statistician. The unblinded statistician will not be involved in any decisions relating to populations for analysis or study decisions prior to unblinding. Documentation and unblinded files will be stored in a secure location and shared with unblinded staff only using sealed envelopes. Interim PK parameter estimations will be performed using bioanalytical data applied with participant aliases. There may be instances where interim PK data have the potential to be treatment revealing. Every effort will be made by the pharmacokineticist to maintain the study blind by appropriate presentation of data to the study team.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Four cohort, single ascending dose, randomised, double-blinded, placebo-controlled study

Study Record Dates

• First Submitted: July 25, 2024
• First Posted: August 19, 2024
• Study Start: August 27, 2024
• Primary Completion: September 3, 2025
• Study Completion: September 3, 2025
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

GB (1)