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

NCT05507970 | Completed Phase 1 Results

• 4 other identifiers: MMV_MMV367_21_012022-000918-33ISRCTN174238511005344
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria,Falciparum

Keywords

Malaria; Healthy Volunteers

Outcome Measures

Primary Outcomes (11)

• Number of Treatment-Emergent Adverse Events (TEAEs)

  Treatment-emergent AEs (TEAEs): AEs that commence during/after the first dose of IMP or commence before first dose of IMP (i.e., a pre-dose AE or existing medical condition) but worsen in intensity during exposure to IMP.

  Screening/day-28 to EoS (End of Study) visit (Day 15 in Part 1, Day 14 in part 2 and Day 17 in part 3). Up to a maximum of 6.5 weeks in total.

• Number of Clinically Significant Physical Examination Findings

  In the targeted (symptom driven) physical examination, a physician will assess the participant; if the participant reports feeling unwell or has ongoing AEs, then the physician will examine the appropriate body system(s) if required.

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2 and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Changes From Baseline for Electrocardiograms (ECGs): RR Interval (The R-R Interval is the Distance Between Two Consecutive R Waves.)

  Clinically important changes in mean values from baseline (individual: Day 1, Pre-dose; mean: Day 1, mean of 3 pre-dose measurements) to any post-dose time point

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2 and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Participants With Changes From Baseline for Laboratory Safety Tests (Haematology, Biochemistry)

  Shifts from within the reference range at baseline to outside the reference range after dosing with IMP.

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2, and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Clinically Important Changes From Baseline for Respiratory Rate

  Clinically important changes in mean values from baseline (Day 1, Pre-dose) to any post-dose time point for any dose level of MMV367 or placebo.

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2,and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Clinically Important Changes in Heart Rate, Supine

  Clinically important changes in mean values from baseline (Day 1, Pre-dose) to any post-dose time point for any dose level of MMV367 or placebo.

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2, and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Clinically Important Changes in Heart Rate, Orthostatic

  Clinically important changes in mean values from baseline (Day 1, Pre-dose) to any post-dose time point for any dose level of MMV367 or placebo.

  Screening/day-28 to Day 7 in Part 1, Day 15 in Part 2, and Day 9 in Part 3, up to a maximum of 6 weeks in total

• Number of Clinically Important Changes From Baseline for Blood Bressure in mmHg: Orthostatic

  Clinically important changes in mean values from baseline (Day 1, Pre-dose) to any post-dose time point for any dose level of MMV367 or placebo.

  Screening/day-28 to Day 7 in Part 1, Day 15 in Part 2, and Day 9 in Part 3, up to a maximum of 6 weeks in total

• Number of Participants With Changes From Baseline For Electrocardiograms (ECGs): QTcF (Corrected QT Interval Using the Fridericia Formula)

  Number of Participants with Out of Range QTcF Values

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2 and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Participants With Changes From Baseline for Electrocardiograms (ECGs): QTcB (Corrected QT Interval Using the Bazett's Formula)

  Number of Participants with Out of Range QTcB Values

  Screening/day-28 to EoS visit (Day 15 in Part 1, Day 14 in part 2 and Day 17 in part 3). Up to a maximum of 6.5 weeks in total

• Number of Clinically Important Changes From Baseline for Blood Pressure in mmHg: Supine

  Clinically important changes in mean values from baseline (Day 1, Pre-dose) to any post-dose time point for any dose level of MMV367 or placebo.

  Screening/day -28 to EoS visit (Day 15 in Part 1, Day 14 in part 2, and Day 17 in Part 3). Up to a maximum of 6.5 weeks in total.

Study Arms (9)

Part 1 Single Ascending Dose Cohort A

EXPERIMENTAL

100 mg MMV367, oral solution, fasted,

Drug: MMV367

Part 1 Single Ascending Dose Cohort B

EXPERIMENTAL

Single ascending dose to be determined after SAC (Safety Advisory Committee) review of previous cohort. Intervention: MMV367, oral solution, fasted

Drug: MMV367

Part 1 Single Ascending Dose Cohort C

EXPERIMENTAL

Single ascending dose to be determined after SAC review of previous cohort. Intervention: MMV367, oral solution, fasted

Drug: MMV367

Part 1 Single Ascending Dose Cohort D

EXPERIMENTAL

Single ascending dose to be determined after SAC review of previous cohort. Intervention: MMV367, oral solution, fasted

Drug: MMV367

Part 1 Single Ascending Dose Cohort Placebo

PLACEBO COMPARATOR

Single ascending dose to be determined after SAC review of previous cohort. Intervention: placebo, oral solution, fasted

Drug: Placebo

Part 2 Food Effect Fed 440mg

EXPERIMENTAL

Open label, 2-period cross-over, randomized, food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV367 determined to be safe in Part 1. MMV367: Single dose dispersed in sterile water.

Drug: MMV367 (Fed 440mg)

Part 3 Multiple Dose Cohort A

EXPERIMENTAL

Double-blinded, randomised, placebo-controlled, multiple-dose study. Intervention: MMV367 oral solution, fasted. Once daily for 3 days.

Drug: MMV367

Part 3 Multiple Dose Cohort A Placebo

PLACEBO COMPARATOR

Double-blinded, randomised, placebo-controlled, multiple-dose study. Intervention: placebo, oral solution, fasted. Once daily for 3 days

Drug: Placebo

Part 2 Food Effect Fasted 440mg

EXPERIMENTAL

Open label, 2-period cross-over, randomized, food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV367 determined to be safe in Part 1.

Drug: MMV367 (Fasted 440mg)

Interventions

MMV367 DRUG

Single dose dispersed in sterile water, fasted.

Part 1 Single Ascending Dose Cohort A; Part 1 Single Ascending Dose Cohort B; Part 1 Single Ascending Dose Cohort C; Part 1 Single Ascending Dose Cohort D

Placebo DRUG

Single Dose dispersed in sterile water, fasted.

Part 1 Single Ascending Dose Cohort Placebo

MMV367 (Fed 440mg) DRUG

Single dose dispersed in sterile water with a high fat meal.

Also known as: Food Effect

Part 2 Food Effect Fed 440mg

MMV367 (Fasted 440mg) DRUG

Single dose dispersed in sterile water fasted.

Also known as: Fasted

Part 2 Food Effect Fasted 440mg

Eligibility Criteria

• Age: 18 Years - 55 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 Demographics and Contraception
• Aged 18 to 55 years inclusive at the time of signing informed consent
• Must agree to adhere to the contraception requirements defined in Section 9.4 Baseline characteristics
• Healthy males or non-pregnant, non-lactating healthy females.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening
• Weight ≥50 kg at screening

You may not qualify if:

• Medical/Surgical History and Mental Health
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
• 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 (supine) at screening or admission outside the range of 90 to 140 mmHg systolic or 50 to 90 mmHg diastolic; and pulse rate outside the range of 45 to 100 bpm, unless deemed not clinically significant by the investigator
• A decrease of SBP (systolic blood Pressure) ≥20 mmHg after 3 min standing and/or a decrease of DBP (diastolic blood Pressure)
• ≥10 mmHg after 3 min standing, at screening
• History or presence of known structural cardiac abnormalities, family history of long QT (measured from the beginning of the QRS complex to the end of the T-wave) 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 (\>210 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 borderline abnormalities may be included if the deviations do not pose a safety risk, and if agreed between the sponsor's medical monitor and the investigator
• Participants with a history of cholecystectomy or gall stones
• Participants with conditions that affect their ability to smell or taste (Part 1 only) including, but not limited to mouth ulcers, gum disease, nasal surgery and smell and/or taste disorders (e.g. dysosmia, dysgeusia, respiratory and/or sinus infection or cold) Physical Examination
• Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening Diagnostic assessments
• Evidence of current SARS-CoV-2 infection (severe acute respiratory syndrome)
• Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1 of protocol). 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

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Quotient Sciences: collaborator
• Swiss BioQuant: collaborator
• Banook Group: collaborator
• The Doctors Laboratory Ltd: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Quotient Sciences

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

Results Point of Contact

• Title: Project Director
• Organization: Medicines for Malaria Venture

info@mmv.org

+41 22 555 03 00

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: August 19, 2022
• Study Start: July 29, 2022
• Primary Completion: January 25, 2023
• Study Completion: January 25, 2023
• Last Updated: January 29, 2025
• Results First Posted: January 29, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)