Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of LAI MMV055 Alone and in Combination With MMV371 in Healthy Participants

NCT07011511 | Recruiting Phase 1

• 1 other identifier: MMV_MMV055_24_01_FIH
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-centre, participant- and investigator-blind, randomised, placebo controlled, single ascending dose study to assess the safety, tolerability and PK of a single dose of IM depot injection(s) of LAI formulations of MMV055 administered alone (Part A) and in combination with MMV371 (Part B) in healthy participants. It is planned to enroll up to 6 sequential cohorts of 8 healthy male participants and healthy female participants of non-childbearing potential in Part A. In Part B, up to 3 sequential cohorts of 8 healthy male participants and healthy non-pregnant, non-lactating female participants will be enrolled. In each cohort, participants will be randomised in a ratio of 6 active investigational medicinal product (IMP) to 2 placebo. Part A of the study will include two components, Parts A1 and A2. Part A1 includes two initial cohorts, with planned doses of 40 and 100mg, respectively. It is intended to document the human elimination T1/2 of MMV055, which will then be used to shorten the proposed End of Study (EOS) of 48 weeks, if possible. 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 IMP or placebo (1 participant each) to assess safety and tolerability (including ISRs). The sentinel group will be dosed concomitantly at least 7 days 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).

Conditions

Malaria, Falciparum

Keywords

Malaria; First In Human; Healthy Volunteers

Outcome Measures

Primary Outcomes (10)

• Safety - Incidence of AEs

  Number of participants with AEs

  From enrollment to the last follow up visit at week 56

• Safety - Incidence of Injection Site Reactions

  Number of participants with Injection Site Reactions

  From enrollment to the last follow up visit at week 56

• Safety - Incidence of physical examination findings

  Number of participants with physical examination findings

  From enrollment to the last follow up visit at week 56

• Safety - Vital signs changes from baseline

  Number of participants with clinically significant vital signs changes from baseline

  From enrollment to the last follow up visit at week 56

• Safety - ECG changes from baseline, QT intervals

  Number and percentage of participants with normal and prolonged QT intervals corrected for Fridericia's correction (i.e. QTcF) and increases in QTcF intervals from baseline

  From enrollment to the last follow up visit at week 56

• Safety - ECG changes from baseline, PR and QRS intervals

  Number and percentage of participants with clinically significant changes in PR and QRS intervals

  From enrollment to the last follow up visit at week 56

• Part 1 only: plasma concentrations of MMV055: Cmax

  Expressed in ng/mL

  From enrollment to the last follow up visit at week 56

• Part 1 only: plasma concentrations of MMV055: AUC(0-last)

  Expressed in ng.h/mL

  From enrollment to the last follow up visit at week 56

• Part 1 only: plasma concentrations of MMV055: AUC(0-inf)

  Expressed in ng.h/mL

  From enrollment to the last follow up visit at week 56

• Part 1 only: plasma concentrations of MMV055: T1/2

  Expressed in hours

  From enrollment to the last follow up visit at week 56

Study Arms (9)

Part A1 Regimen A

EXPERIMENTAL

Drug: MMV055 Dose 1; Drug: Matching placebo Part A

Part A1 Regimen B

EXPERIMENTAL

Drug: MMV055 Dose 2; Drug: Matching placebo Part A

Part A2 Regimen C

EXPERIMENTAL

Drug: MMV055 Dose 3; Drug: Matching placebo Part A

Part A2 Regimen D

EXPERIMENTAL

Drug: MMV055 Dose 4; Drug: Matching placebo Part A

Part A2 Regimen E

EXPERIMENTAL

Drug: MMV055 Dose 5; Drug: Matching placebo Part A

Part A2 Regimen F

EXPERIMENTAL

Drug: MMV055 Dose 6; Drug: Matching placebo Part A

Part B Combination 1

EXPERIMENTAL

Drug: Matching placebo Part B; Combination Product: MMV055/MMV371 Combo 1

Part B Combination 2

EXPERIMENTAL

Drug: Matching placebo Part B; Combination Product: MMV055/MM371 Combo 2

Part B Combination 3

EXPERIMENTAL

Drug: Matching placebo Part B; Combination Product: MMV055/MMV371 Combo 3

Interventions

MMV055 Dose 1 DRUG

40mg

Part A1 Regimen A

MMV055 Dose 2 DRUG

100mg

Part A1 Regimen B

MMV055 Dose 3 DRUG

200mg

Part A2 Regimen C

MMV055 Dose 4 DRUG

400mg

Part A2 Regimen D

MMV055 Dose 5 DRUG

800mg

Part A2 Regimen E

MMV055 Dose 6 DRUG

TBCmg

Part A2 Regimen F

Matching placebo Part A DRUG

Part A

Part A1 Regimen A; Part A1 Regimen B; Part A2 Regimen C; Part A2 Regimen D; Part A2 Regimen E; Part A2 Regimen F

Matching placebo Part B DRUG

Part B

Part B Combination 1; Part B Combination 2; Part B Combination 3

MMV055/MMV371 Combo 1 COMBINATION_PRODUCT

Combination 1

Part B Combination 1

MMV055/MM371 Combo 2 COMBINATION_PRODUCT

Combination 2

Part B Combination 2

MMV055/MMV371 Combo 3 COMBINATION_PRODUCT

Combination 3

Part B Combination 3

Eligibility Criteria

• Age: 18 Years - 60 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 60 years inclusive at the time of signing informed consent
• Must agree to adhere to the contraception requirements defined in the study protocol
• Healthy male or healthy WONCBP (Parts A and B), or healthy non-pregnant, non-lactating female participants (Part B only) according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs, 12-lead ECG, and laboratory safety tests without any clinically significant abnormalities. Safety bloods, urinalysis, ECGs and vital signs to be re-checked at admission and/or pre-dose
• Body mass index (BMI) of 19.0 to 30.0 kg/m2 as measured at screening
• 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 (Parts A and B), Wellvone®/Mepron® and/or Malarone® (Part B only)
• 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 GI disease, neurological or psychiatric disorder, as judged by the investigator
• Family history of sudden death, or family history of clinically significant cardiovascular disease, as judged by the investigator
• Systolic BP \>140 or \<90 mmHg, diastolic BP \>90 or \<50 mmHg, or heart rate (HR) (based on vital signs assessment) \>100 or \<45 bpm, confirmed by repeat assessment at screening
• Any finding in the medical examination (including BP, HR or ECG) deviating from normal and assessed as clinically relevant 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 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 based on the mean of the triplicate values and confirmed by single repeat assessment at screening
• 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 or gluteal 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 the study protocol). Participants with Gilbert's Syndrome are not allowed
• Dyslipidaemia (cholesterol and/or triglycerides) requiring pharmacological intervention or fasting triglycerides \>2.26 mmol/L, fasting cholesterol \>6.20 mmol/L, low density lipoprotein cholesterol \>3.75 mmol/L)
• Fasting blood glucose ≥6.1 mmol/L
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results

Sponsors & Collaborators

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

Study Sites (1)

Quotient Sciences

Nottingham, United Kingdom, NG11 6JS, United Kingdom

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Stephan Chalon, MD, PhD

CONTACT

+41 22 555 03 00; chalons@mmv.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: June 8, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): December 2, 2027
• Study Completion (Estimated): December 2, 2027
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

GB (1)