None listed
Conditions
Brief summary
This is a single-centre study using a QIMR3D7Pf innoculum challenge to assess the infectivity of this recently collected isolate. The study will be a first in human study conducted in 2 participants. A sentinel volunteer will be dosed 24 h ahead of the remaining volunteer.
Interventions
This is a single-centre, study using blood stage malaria infected red blood cells inoculum challenge in order to characterize the infectivity of the in vitro expanded Plasmodium falciparum QIMR3D7Pf in healthy volunteers. The study will be conducted in 2 individuals. Each participant in the cohort will be inoculated on Day 0 with ~1,800 viable Plasmodium falciparum-in vitro infected human erythrocytes administered intravenously. On an outpatient basis, participants will be monitored daily prior
This is a single-centre, study using blood stage malaria infected red blood cells inoculum challenge in order to characterize the infectivity of the in vitro expanded Plasmodium falciparum QIMR3D7Pf in healthy volunteers. The study will be conducted in 2 individuals. Each participant in the cohort will be inoculated on Day 0 with ~1,800 viable Plasmodium falciparum-in vitro infected human erythrocytes administered intravenously. On an outpatient basis, participants will be monitored daily prior to detection of parasites or morning (AM) and evening (PM) (once PCR positive for presence of malaria parasites) from day 3 to day 7 for adverse events and the unexpected early onset of symptoms, signs or parasitological evidence of malaria. On the day designated for commencement of treatment, as determined by qPCR results (expected to be Day 7), participants will be admitted to the study unit and confined for safety monitoring and antimalarial treatment. The threshold for commencement of treatment will be when PCR quantification is confirmed to be approximately =1,000 parasites/mL when the participants will be administered antimalarial treatment. If clinical evidence of malaria (the onset of clinical features of malaria) occurs or PCR quantification of =1,000 parasites/mL is detected before day 7 morning, allocated treatment will begin at this time. Following treatment, participants will be followed up as inpatients for at least 36 hours, to ensure tolerance of the therapy and clinical response, then if clinically well on an outpatient basis for monitoring of, safety and clearance of malaria parasites via PCR.
Sponsors
Queensland Institute of Medical Research
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants will be adults (males or non pregnant females), aged between 18 and 45 years who do not live alone (from Day 1 until at least the end of the antimalarial drug treatment). 2. Participants must have a BMI within the range 18–30 kg/m2. 3. Participants must understand the procedures involved and agree to participate in the study by giving fully informed, written consent. 4. Be contactable and available for the duration of the trial (maximum of 4 weeks). 5. Participants must be non-smokers and in good health, as assessed during pre-study medical examination and by review of screening results. 6. Female participants of childbearing potential, should be surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the US FDA or TGA combined with a barrier contraceptive through completion of the study and have negative results on a serum or urine pregnancy test done before administration of study medication. 7. Good peripheral venous access.
Exclusion criteria
1. History of malaria or tavelled to or lived (greater than 2 weeks) in a malaria-endemic country during the past 12 months 2. Has evidence of increased cardiovascular disease risk 3. History of splenectomy. 4. History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion. 5. Presence of current or suspected serious chronic diseases or significant intercurrent disease of any type 6. Unwilling to defer blood donations for 6 months. 7. Recent or current therapy with an antibiotic or drug with potential antimalarial activity (tetracycline, azthromycin, clindamycin, hydroxychloroquine etc.). 8. Concomitant use of any drug which is metabolised by the cytochrome enzyme CYP2D6 9. Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. 10. Presence of acute infectious disease or fever 15. Evidence of acute illness within the four weeks before trial prior to screening. 11. Alcohol consumption greater than community norms (i.e. more than 21 standard drinks per week for males). 12. A history of drug habituation, or any prior intravenous usage of an illicit substance. 13. Medical requirement for intravenous immunoglobulin or blood transfusions. 14. Participation in any investigational product study within the 8 weeks preceding the study. 15. Any clinically significant biochemical or haematologic abnormality 16. Vital signs outside the reference range and clinically significant.
Outcome results
None listed