Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612000814875
Ethics application status
Approved
Date submitted
1/08/2012
Date registered
3/08/2012
Date last updated
28/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
An experimental study to characterize the effectiveness of OZ439 against early Plasmodium falciparum blood stage infection in healthy volunteers.
Scientific title
An experimental study to characterize the effectiveness of OZ439 against early Plasmodium falciparum blood stage infection in healthy volunteers.
Secondary ID [1] 280950 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 287047 0
Condition category
Condition code
Infection 287375 287375 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single centre study using blood stage Plasmodium falciparum challenge inoculum to characterise the effectiveness of OZ439 against early blood stage Plasmodium Falcipaurm infection.The study will be conducted in up to 3 cohorts (8 particpants in each) using different doses of OZ439. Subsequent cohorts will not commence until at least after day 15 of the previous cohort and review by Safety Review Team following day 14 of the previous cohort. The first dose of OZ439 investigated will be a single dose of 100 mg. Subsequent doses in subsequent cohort(s) will be determined following safety and efficacy data review by the Safety Review Team. It is anticipated that subsequent doses will be between 50-200mg. The drug will be administered orally. OZ439 is the accronym for the drug.
Intervention code [1] 285384 0
Treatment: Drugs
Comparator / control treatment
There is no comparison treatment as this trial is not randomised within cohort i.e.all subjects in each cohort get the same treatment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287648 0
To characterize the pharmacokinetic-pharmacodynamic relationship of OZ439 on clearance of Plasmodium falciparum parasites from the blood in healthy volunteers following infection with blood stage parasites. This outcome will be assessed by measuring drug levels and parasite levels and assessing changes in both.
Timepoint [1] 287648 0
30 Days
Secondary outcome [1] 298579 0
To characterize the pharmacokinetics of OZ439 in healthy volunteers following infection with blood stage Plasmodium falciparum. This outcome will be assessed by measuring drug levels in blood.
Timepoint [1] 298579 0
6 days
Secondary outcome [2] 298580 0
To assess the tolerability ofOZ439 in the experimental malaria challenge system. This outcome will be measured by soliciting adverse events in volunteers, and by blood laboratory safety tests, including biochemistry and haematology screen, viral and infectious disease serology, and red cell alloantibody screen.
Timepoint [2] 298580 0
30 days

Eligibility
Key inclusion criteria
1. Volunteers 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. Volunteers must have a BMI within the range 18–30.
3. Volunteers 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. Volunteers 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.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) History of malaria.
2) Travelled to or lived (2 weeks or more) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study. 3) Has evidence of increased cardiovascular disease risk (defined as greater than 10%, 5 year risk)
4) History of splenectomy.
5) History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.
6) Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.
7) Known inherited genetic anomaly (known as cytogenetic disorders) e.g., Down’s syndrome
8) Volunteers unwilling to defer blood donations to the ARCBS for 6 months.
9) The volunteer has a diagnosis of schizophrenia, severe depression, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis. Participants who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating may be allowed to enroll in the study at the investigator’s discretion. 10) Presence of acute infectious disease or fever (e.g., sub-lingual temperature 38.5 degrees C) within the five days prior to study product administration.
11) Evidence of acute illness within the four weeks before trial prior to screening.
12) Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical examination, and/or laboratory studies including urinalysis.
13) Have ever received a blood transfusion.
14) Evidence of any condition that, in the opinion of the clinical investigator, might interfere with the evaluation of the study objectives or pose excessive risks to participants.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Three groups of participants receive different doses of the same intervention at different times. (i.e. not concurrently)
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/09/2012
Actual
6/09/2012
Date of last participant enrolment
Anticipated
Actual
21/01/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285739 0
Charities/Societies/Foundations
Name [1] 285739 0
Medicines of Malaria Venture
Country [1] 285739 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Queensland Institute of Medical Research
Address
300 Herston Rd, Herston,Brisbane, Queensland, 4006
Country
Australia
Secondary sponsor category [1] 284562 0
None
Name [1] 284562 0
Address [1] 284562 0
Country [1] 284562 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287744 0
The Queensland Institute of Medical Research Human Research Ethics Committee
Ethics committee address [1] 287744 0
The Queensland Institute of Medical Research, Post Office Royal Brisbane,QLD, 4029
Ethics committee country [1] 287744 0
Australia
Date submitted for ethics approval [1] 287744 0
21/06/2012
Approval date [1] 287744 0
03/08/2012
Ethics approval number [1] 287744 0
P1470

Summary
Brief summary
This is a single-center study using a blood stage Plasmodium falcipaurm challenge (BSPC) inoculum to characterize the effectiveness of OZ439 against early Plasmodium falciparum blood stage infection. The study will be conducted in up to 3 cohorts using different doses of OZ439.
Trial website
Trial related presentations / publications
A DOSE RANGING STUDY IN THE HUMAN INDUCED BLOOD
STAGE MALARIA MODEL TO DEFINE THE ANTIPARASITIC
ACTIVITY AND PHARMACOKINETIC-PHARMACODYNAMIC
RELATIONSHIP OF THE SYNTHETIC PEROXIDE
ANTIMALARIAL OZ439, scientific session, American Society of Tropical Medicine and Hygiene, Washington, November 2013
Public notes

Contacts
Principal investigator
Name 34517 0
Dr Dr James McCarthy
Address 34517 0
Queensland Insitute of Medical Research 300 Herston Rd Herston QLD 4006
Country 34517 0
Australia
Phone 34517 0
+61 7 3845 3796
Fax 34517 0
Email 34517 0
[email protected]
Contact person for public queries
Name 17764 0
Ms Silvana Sekuloski
Address 17764 0
Queensland Insitute of Medical Research 300 Herston Rd Herston QLD 4006
Country 17764 0
Australia
Phone 17764 0
+61738453856
Fax 17764 0
+61738453507
Email 17764 0
[email protected]
Contact person for scientific queries
Name 8692 0
Ms Silvana Sekuloski
Address 8692 0
Queensland Insitute of Medical Research 300 Herston Rd Herston QLD 4006
Country 8692 0
Australia
Phone 8692 0
+61738453856
Fax 8692 0
+61738453507
Email 8692 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePlasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+T Cell Population with Cytotoxic Potential.2016https://dx.doi.org/10.1371/journal.pntd.0005031
Dimensions AIReduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels2021https://doi.org/10.1186/s12936-021-03642-0
Dimensions AIAnalysis of Breath Specimens for Biomarkers of Plasmodium falciparum Infection2015https://doi.org/10.1093/infdis/jiv176
Dimensions AIEfficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers2016https://doi.org/10.1093/jac/dkw174
Dimensions AIProfoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection2016https://doi.org/10.1128/iai.01522-15
Dimensions AIPlasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation2017https://doi.org/10.1038/s41598-017-02096-2
Dimensions AIPlasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria2018https://doi.org/10.1093/infdis/jiy555
N.B. These documents automatically identified may not have been verified by the study sponsor.