MMV533 Plasmodium Falciparum Volunteer Infection Study
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

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
    

Detailed description: 
      The study will characterise the effects of single oral doses of MMV533 on the clearance of
      Plasmodium falciparum 3D7 using the IBSM model. This is a well-established method for
      obtaining useful pharmacokinetic-pharmacodynamic (PK-PD) information on anti-malarial drugs.

      The study will be an open-label, pilot Volunteer Infection Study (VIS) using the IBSM model
      and single dose IMP. The study will be conducted in healthy malaria-naive adult volunteers
      infected with Plasmodium falciparum 3D7, in one cohort of approximately 12 volunteers (all
      receiving active treatment). From an operational perspective, the full cohort may be
      conducted in subgroups of up to 6 volunteers. Ascending doses will be administered in order
      of enrolment number (per sub-group, if applicable). Volunteers will be enrolled within a 28
      day screening period to ensure volunteers meet all the inclusion criteria and none of the
      exclusion criteria.

      On Day -8 (8 days prior to IMP administration), volunteers will attend the clinical unit to
      be inoculated with the malaria challenge agent containing approximately 2,800 viable human
      erythrocytes infected with P. falciparum 3D7 parasites. Parasitaemia will be monitored on an
      outpatient basis daily on Day -4, and then twice daily on Day -3, Day -2 and until admission
      to the clinical unit on Day -1 for eligibility check and confinement.

      Volunteers will be administered IMP on Day 1 and will have safety monitoring and blood
      sampling for parasitaemia monitoring and PK analysis on an inpatient basis for at least 108
      hours post-IMP administration. Volunteers will be discharged from the clinical unit after
      review of ECG, vital signs, clinical and laboratory tests safety data by the Principal
      Investigator or delegate, and will then attend the clinical unit on an outpatient basis
      regularly for continued safety monitoring and blood sampling for parasitaemia monitoring and
      PK analysis.

      Volunteers will be administered mandatory malaria rescue medication at Day 21±3, or earlier
      if there is failure to clear parasites or recrudescence and at the discretion of the
      Principal Investigator or delegate. EOS will be on Day 28±3. Volunteers must have had at
      least two negative 18S qPCR results prior to EOS and must have completed their course of
      anti-malarial rescue medication.

      In the event of recrudescence, blood samples will be collected prior to rescue treatment to
      culture parasites for drug resistance testing.
    

Intervention name(s): MMV688533
Intervention type(s): Drug
Intervention description(s): Not exceeding 200mg
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tolerability; Safety