MMV533 Plasmodium Falciparum Volunteer Infection Study

NCT05205941 | Completed Phase 1 Results DMC

• 1 other identifier: MMV_MMV533_20_01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1b study to assess the safety, tolerability and antimalarial activity of MMV533 against Plasmodium falciparum 3D7 blood stage infection in healthy volunteers

Conditions

Malaria

Keywords

Tolerability; Safety

Outcome Measures

Primary Outcomes (7)

• The Activity of Single Oral Doses of MMV533 (Name of Investigational Medicinal Product) on Clearance of Plasmodium

  Estimated Parasite Reduction Ratio over 48 hours (PRR48)

  48 hours

• The Activity of Single Oral Doses of MMV533 (Name of Investigational Medicinal Product) on Clearance of Plasmodium

  Estimated Parasite Reduction Ratio over 48 hours (log10 PRR48)

  48 hours

• The Activity of Single Oral Doses of MMV533 (Name of Investigational Medicinal Product) on Clearance of Plasmodium

  Parasite Clearance Half-life after Single Oral Dose of MMV533, by Treatment Group

  48 hours

• Participants With Parasitaemia Below Limit of Quantification (LOQ)

  Number of volunteers whose parasitaemia levels fall below limit of quantification (LOQ) following treatment with IMP

  48 hours

• Activity of Single Oral Doses of MMV533 on Clearance of Plasmodium

  The Total Number of Study Participants with Recrudescence of Asexual Parasitaemia within 30 days post inoculation

  30 days post inoculation

• The Activity of Single Oral Doses of MMV533 on Clearance of Plasmodium

  Number of participants experiencing a recrudescence after 180 hours

  180 hours post inoculation

• The Activity of Single Oral Doses of MMV533 on Clearance of Plasmodium

  Number of participants experiencing a recrudescence after 312 hours

  312 hours post inoculation

Study Arms (1)

MMV533 (single, oral doses).

OTHER

Approximately 12 volunteers in 1 cohort, Up to six dose levels between 10 and 160mg

Drug: MMV688533

Interventions

MMV688533 DRUG

Not exceeding 200mg

Also known as: MMV533

MMV533 (single, oral doses).

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Having given written informed consent prior to undertaking any study-related procedure.
• Male or female aged between 18 to 55 years inclusive.
• Available for the duration of the study and for 2 weeks following the End of Study Visit (EOS).
• Lives with a spouse, family member, or housemate from the time of inoculation with the malaria challenge agent through to the EOS.
• Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive).
• Willing to defer blood donations to a blood service for a minimum of 6 months after the EOS.
• Heterosexual women of childbearing potential (WOCBP) must agree to the use of a highly effective method of birth control (see below) combined with a barrier contraceptive from the screening visit until 30 days after the last dose of the IMP (covering a full menstrual cycle of 30 days starting after 5 half-lives of last dose of IMP) and have a negative result on urine pregnancy test performed before inoculation with the malaria challenge agent.
• Women of non-childbearing potential (WONCBP)
• Males who have, or may have female sexual partners of child bearing potential during the course of the study must agree to use a double method of contraception including condom plus diaphragm, or condom plus intrauterine device, or condom plus stable oral/transdermal/injectable/implantable hormonal contraceptive by the female partner, from the time of informed consent through to 60 days (covering a spermatogenesis cycle) after the last dose of the IMP. Abstinent males must agree to start a double method if they begin sexual relationship with a female during the study and up to 60 days after the last dose of study drug. Males with female partners of child-bearing potential that are surgically sterile, or males who have undergone sterilisation and have had testing to confirm the success of the sterilisation, may also be included and will not be required to use above described methods of contraception.
• Vital signs after 5 minutes resting in supine position:
• Systolic blood pressure (SBP) - 90-140 mmHg,
• Diastolic blood pressure (DBP) - 40-90 mmHg,
• Heart rate (HR) 40-100 bpm.
• At Screening and pre-inoculation with the malaria challenge agent: normal standard mean of triplicate 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position in the following ranges:
• QT ≤ 500 msec,

You may not qualify if:

• Any lifetime history of malaria or participation in a previous malaria challenge study or malaria vaccine trial.
• Must not have had malaria exposure that is considered significant by the Principal Investigator or delegate. This includes but is not limited to:
• history of having travelled to or lived (\> 2 weeks) in a malaria-endemic region during the past 12 months or planned travel to a malaria-endemic region during the course of the trial;
• history of having lived for \>1 year in a malaria-endemic region in the past 10 years;
• history of having ever lived in a malaria-endemic region for more than 10 years inclusive. For endemic regions see https://malariaatlas.org/explorer/#/ Bali is not considered a malaria-endemic region.
• Presence of acute infectious disease and/or abnormal body temperature (defined as an a.m. tympanic temperature \>37.5 ºC or a p.m. \>37.7 ºC) at pre-inoculation.
• Haematology, biochemistry or urinalysis results that are outside of the laboratory normal reference ranges and are either:
• considered clinically significant by the Principal Investigator or delegate; OR
• considered not clinically significant by the Principal Investigator or delegate but are also outside of Sponsor-approved clinically acceptable laboratory ranges
• Breastfeeding or lactating; positive serum pregnancy test at screening, positive urine pregnancy test upon admission or at other timepoints as specified by schedule of activities tables.
• Has previously received a blood transfusion.
• Use of antibiotics within 6 weeks of Screening.
• Use of systemic therapies with antimalarial activity within 6 weeks of Screening. This includes (but not limited to) artemisinin, amodiaquine, atovaquone, chloroquine, mefloquine, mepacrine, primaquine, proguanil, quinine, sulfadoxine-pyrimethamine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, doxycycline, and tafenoquine.
• Prior to screening and inoculation with the malaria challenge agent:
• any systemic administration (oral, pulmonary/nasal, IV) of corticosteroids, anti-inflammatory drugs (excluding commonly used over-the-counter anti-inflammatory drugs such as ibuprofen, acetylsalicylic acid, diclofenac), immunomodulators or anticoagulants within the past three months.

Sponsors & Collaborators

• Medicines for Malaria Venture: lead
• Nucleus Network Ltd: collaborator
• Southern Star Research: collaborator

Study Sites (1)

Nucleus Network Brisbane Clinic

Brisbane, Queensland, 4006, Australia

Location

Related Publications (1)

• Bestgen B, Jones S, Thathy V, Kuemmerle A, Barcelo C, Haouala A, Gossen D, Marx MW, Di Resta I, Szramowska M, Webster RA, Llewellyn S, Ritacco DA, Yeo T, Leroy D, Barber BE, Fidock DA, Griffin P, Lickliter J, Chalon S. Safety, tolerability, pharmacokinetics, and antimalarial activity of MMV533: a phase 1a first-in-human, randomised, ascending dose and food effect study, and a phase 1b Plasmodium falciparum volunteer infection study. Lancet Infect Dis. 2025 May;25(5):507-518. doi: 10.1016/S1473-3099(24)00664-9. Epub 2024 Dec 18.

  PMID: 39708824 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Benoit Bestgen
• Organization: MMV

bestgenb@mmv.org

+41797651868

Study Officials

• Jason Lickliter, MD

  Nucleus Network Ltd

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2021
• First Posted: January 25, 2022
• Study Start: March 30, 2022
• Primary Completion: September 2, 2022
• Study Completion: September 2, 2022
• Last Updated: December 2, 2024
• Results First Posted: December 2, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)