None listed
Conditions
Brief summary
This is a single-centre, controlled, study using induced blood stage malaria (IBSM) infection to characterize the effectiveness of ferroquine as a potential treatment of early Plasmodium falciparum blood stage infection in healthy volunteers. The study will be conducted in 2 cohorts (n= 8 in each) using different oral doses of ferroquine.
Interventions
This is a single-centre, controlled, study using induced blood stage malaria (IBSM) infection to characterize the effectiveness of ferroquine against early Plasmodium falciparum blood stage infection. The study will be conducted in 2 cohorts (n= 8 in each). Each participant in the cohort will be inoculated on Day 0 with ~1,800 viable Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. On the day designated for commencement of treatment, as determined by qPCR resu
This is a single-centre, controlled, study using induced blood stage malaria (IBSM) infection to characterize the effectiveness of ferroquine against early Plasmodium falciparum blood stage infection. The study will be conducted in 2 cohorts (n= 8 in each). Each participant in the cohort will be inoculated on Day 0 with ~1,800 viable Plasmodium falciparum-infected human erythrocytes (BSPC) administered intravenously. On the day designated for commencement of treatment, as determined by qPCR results, participants will begin treatment with ferroquine. The threshold for commencement of treatment will be when PCR quantification of all subjects is greater than or equal to 1,000 parasites/mL. If the PCR quantification of a subject is greater than or equal to 5,000 parasites/mL or if clinical or parasitological evidence of malaria occurs in a subject, before all subjects have reached the treatment threshold, of =1,000 parasites/mL then allocated treatment of that subject will begin at this time . It is expected that treatment will commence 7-8 days following inoculation. The first cohort will be dosed with a single oral dose of 800mg ferroquine. The subsequent dose in the second cohort will be determined following a review of observed ferroquine safety, and pharmacodynamic outcome (activity of the drug as defined by parasite clearance kinetics). It is anticipated that the subsequent dose will be between 300mg and 1200mg. Cohort 1 data will be reviewed by the by Safety Review Team, to determine cohort 2 start date and dose. All participants will be administered Riamet which is a standard treatment for Malaria at the end of study to ensure clearance of parasites.
Sponsors
QIMR Berghofer Medical Research Institute
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Demography: *Male and non-pregnant female volunteers, between 18 and 50 years of age, inclusive; Body weight, minimum 50.0 kg, body mass index between 18.0 and 32.0 kg/m2, inclusive. Health status: *Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination), including normal vital signs *Normal standard 12-lead electrocardiogram (ECG) *Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects. *Female volunteers not to have childbearing potential through completion of the study and have negative results on a serum pregnancy test done before administration of study medication. *Male volunteers must agree to use appropriate protection to prevent pregnancy in female partner for at least 14 days prior to the time of the first dose of study drug through 90 days after the last dose of study drug Regulations: *Having given written informed consent prior to undertaking any study-related procedure.
Exclusion criteria
Medical history and clinical status: *Any history of malaria or having travelled to or lived in a malaria-endemic country during the past 12 months. *Increased cardiovascular disease risk *History of splenectomy. *Pregnant or breast feeding *Presence or history of drug hypersensitivity, or allergic disease *Presence of current or suspected serious chronic diseases including psychiatric illness *Evidence of acute illness within the four weeks before trial prior to screening. *Condition or disease that might affect drug absorption, distribution or excretion *Participation in any investigational product study within the 8 weeks preceding the study. *Participation in any research study involving significant blood sampling, or blood donation to Red Cross (or other) blood bank during the 8 weeks preceding the reference drug dose in the study. *Volunteer unwilling to defer blood donations to the ARCBS for 6 months. *Volunteer who have ever received a blood transfusion. *History or presence of alcohol or drug abuse *Smoking more than 5 cigarettes or equivalent per day Interfering substance: *Any medication (including St John’s Wort or therapy with an antibiotic or drug with potential antimalarial activity (tetracycline, azithromycin, clindamycin, hydroxychloroquine etc.) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, any vaccination within the last 28 days. General conditions: *Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development. *Any subject who do live alone (from Day 0 until at least the end of the antimalarial drug treatment and who cannot be contacted in case of emergency for the duration of the trial and up to 2 weeks following end of study visit. *Any subject without a good peripheral venous access. Biological status: *Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab), *Any illicit drugs in the urine drug screen unless there is an explanation acceptable to the medical investigator or Positive alcohol test. *Known hypersensitivity to ferroquine or other 4-aminoquinolines, artemether or other artemisinin derivatives, lumefantrine or other arylaminoalcohols. *Unwillingness to abstain from consumption of citrus (grapefruit, Seville orange, etc) or their juices, as well as all fruit juices, from admission to the clinical unit until Day 28 (End of Study) visit. *Any history or presence of lactose intolerance.
Outcome results
None listed