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Trial registered on ANZCTR


Registration number
ACTRN12614000930684
Ethics application status
Approved
Date submitted
20/08/2014
Date registered
29/08/2014
Date last updated
20/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
An experimental study to characterize the in vivo safety and infectivity of the Plasmodium vivax isolate HMPBS02-Pv in humans
Scientific title
Blood stage challenge pilot study to assess the safety and the infectivity of Plasmodium vivax isolate HMPBS02-Pv in healthy volunteers.
Secondary ID [1] 285194 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Experimental malaria infection 292800 0
Condition category
Condition code
Infection 293096 293096 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-centre study using a naturally acquired P. vivax HMPBS02-Pv challenge inoculum to infect healthy participants in order to characterize the in vivo infectivity of the parasite isolate P. vivax HMPBS02-Pv. This study will be conducted in two consenting and eligible participants. Each participant will be inoculated on Day 0 with around 100 viable P. vivax-infected human erythrocytes administered intravenously.
On an outpatient basis, the participants will be monitored by PCR for presence of malaria parasites and for unexpected early onset of malaria symptoms, signs or parasitological evidence of malaria. On the day designated for commencement of treatment, participants will be admitted to the study unit and confined for safety monitoring and anti-malarial treatment with the antimalarial drug Riamet (artemether 20mg/lumefantrine 120mg). This treatment will be administered as an oral tablet; 6 doses of 4 tablets (total course 24 tablets) given over a period of 60 hours following food. All doses with exception of the last will be given under direct observation of clinical staff. It is expected the last dose is taken by participants at home. Participants will have a phone call from a study staff member to check on symptoms and ensure compliance/completion with treatment following the dose taken at home.
At commencement of antimalarial treatment, the participants will be followed as inpatients for 48 hours to ensure tolerance of therapy and clinical response. Once clinically well, the participants will be followed up on an outpatient basis for continued dosing of anti-malarial drug, safety and clearance of malaria parasites via qPCR. Follow up visits for safety assessments will be performed on Day 28 and Day 90 after malaria infection and the participants are required to be contactable and available up to 2 weeks following this end of study visit. The overall period of participation will therefore be around 14 weeks from the time malaria infection.
Intervention code [1] 290061 0
Treatment: Drugs
Comparator / control treatment
n/a
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292963 0
Primary Outcome 1: To determine the safety of an experimental malaria challenge using naturally occurring parasites.
Assessed by close monitoring of clinical status, including physical examination vital signs electrocardiograms (ECG) and by laboratory pathology testing, including hematology, chemistry, and serology including serologic assessment for evidence of seroconversion to adventitious agents.
Clinical safety will be also be assessed by soliciting symptoms and signs of malaria (such as fever fatigue, vomiting and Diarrhea) and of adverse effects of the inoculum.
Timepoint: Adverse event (AE) screening through to Day 16, Day 28, 90. All AEs reported by the participants, will be recorded and the investigator will determine if the reported AEs are related to the malaria infection or not. General AEs that might occur due to inoculum could include but not limited to Headache, Chills, Feeling tired/lethargy, Muscular pain, Malaise or Nausea.
Physical examination and vital signs: Screening, Day 0 and 7-28, 90
Hematology, biochemistry : screening, Day 0,14, 16, 28
Timepoint [1] 292963 0
Adverse event screening through to Day 16, Day 28, 90
Physical examination and vital signs: Screening, Day 0 and 7-28, 90
Hematology, biochemistry : screening, Day 0,14, 16, 28
ECG: Screening and Day 28
Serology: Screening and Day 28, 90
Primary outcome [2] 292964 0
To characterize the in vivo infectivity of P. vivax isolate HMPBS02-Pv in healthy participants following infection with blood stage parasites.

Assessed by close monitoring of the number of parasites in the blood and clinical symptoms of malaria
Timepoint [2] 292964 0
Pre inoculation on Day 0 and then daily from Day 7 until PCR positive for malaria, then twice daily until Riamet (Registered Trademark) dosing, at scheduled time points through confinement and then daily until two consecutive negative PCR and Day 28
Secondary outcome [1] 310027 0
To define the parasite growth curves after I.V. inoculation of healthy participants with naturally acquired P. vivax blood stage parasites
Assessed by PCR testing of collected blood
Timepoint [1] 310027 0
At baseline and at day 7-14
Secondary outcome [2] 310028 0
To explore the parasite clearance profiles by PCR after administration of antimalarial drug at a target parasitemia of greater than or equal to 1,000 parasites/mL after inoculation with an experimental malaria challenge.
Assessed by PCR testing of collected blood
Timepoint [2] 310028 0
Following antimalarial treatment on day 14 to 16 and day 28

Eligibility
Key inclusion criteria
1) Healthy adults (male or female) subjects, who do not live alone (from Day 0 until at least the end of the antimalarial drug treatment) and be contactable and available for the duration of the trial (maximum of 4 months).
2) Body weight, minimum 50.0 kg, body mass index between 18.0 and 32.0 kg/m2, inclusive.
3) Female participants of childbearing potential should be blood group Rh positive and have adequate contraception in place.
4) Able and willing (in the Investigator’s opinion) to give consent and comply with all study requirements.
5) Non-smokers or smoking not more than 5 cigarettes per day and able to stop smoking during the confinement period in the study.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) History of clinical malaria or participation to a previous malaria challenge studies, or travel 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) Pregnant or breast feeding
4) History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.
5) Being unwilling to defer blood donations for the duration of the trial and for at least 6 months after the end of their involvement in the study.
6) A history of clinically significant ECG abnormalities and known pre-existing prolongation of the QTc interval considered clinically significant.
7) Subject who has ever received a blood transfusion, and females of child bearing potential who are blood group Rh negative.

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
Single group
Other design features
It is planned to dose a sentinel participant initially. Following dosing of the initial participant, and review by the PI and the Medical Monitor following approximately 24 hours review of the participant’s clinical status, the second participant will be dosed.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
As this is a pilot infectivity study no assessment of dose characteristics for the HMPBS02-Pv will be undertaken. Growth and clearance of parasitaemia will be compared to data on hand.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 8624 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 289807 0
Government body
Name [1] 289807 0
The National Health and Medical Research Council (NHMRC)
Address [1] 289807 0
Level 1, 16 Marcus Clarke Street, Canberra ACT 2601
Country [1] 289807 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Road, Herston, Brisbane, QLD, 4006
Country
Australia
Secondary sponsor category [1] 288501 0
None
Name [1] 288501 0
Address [1] 288501 0
Country [1] 288501 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291540 0
QIMR Berghofer Medical Research Institute Human Research Ethics Committee
Ethics committee address [1] 291540 0
300 Herston Rd
Herston QLD 4006
Ethics committee country [1] 291540 0
Australia
Date submitted for ethics approval [1] 291540 0
22/07/2014
Approval date [1] 291540 0
22/08/2014
Ethics approval number [1] 291540 0
P2063

Summary
Brief summary
The goal of this single-centre study is to establish a ‘universal’, blood group O bank, of P. vivax infected human red blood cells (RBCs) for use in future malaria challenge studies. The study will use P. vivax HMPBS02-Pv challenge inoculum to infect two healthy participants in order to characterize the safety and infectivity of the parasite isolate P. vivax HMPBS02-Pv in vivo.

Each participant will be inoculated on Day 0 with around 100 viable P. vivax-infected RBCs administered intravenously. The participants will be monitored for malaria symptoms firstly by phone, and then on an outpatient basis, for the unexpected early onset of malaria symptoms and for malaria parasites by PCR.

On the day designated for commencement of treatment, as determined by PCR results and/or onset of clinical symptoms, participants will be admitted to the study unit and confined for safety monitoring and anti-malarial treatment (Riamet (Registered Trademark'))

Following initiation of anti-malarial treatment, the participants will be monitored as in-patients for 48 hours to ensure tolerance of therapy and clinical response. Once clinically well, the participants will be followed up on an out-patient basis for continued dosing of anti-malarial drug, safety and clearance of malaria parasites via PCR. Follow up visits for safety assessments will be performed on Day 28 and Day 90 after malaria infection.
Trial website
Trial related presentations / publications
none to date
Public notes

Contacts
Principal investigator
Name 50798 0
Dr James McCarthy
Address 50798 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 50798 0
Australia
Phone 50798 0
+61 7 3362 0222
Fax 50798 0
+61 7 3845 3637
Email 50798 0
j.mccarthy@uq.edu.au
Contact person for public queries
Name 50799 0
Dr Silvana Sekuloski
Address 50799 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 50799 0
Australia
Phone 50799 0
+61 7 3845 3856
Fax 50799 0
+61 7 3845 3507
Email 50799 0
Silvana.Sekuloski@qimrberghofer.edu.au
Contact person for scientific queries
Name 50800 0
Dr James McCarthy
Address 50800 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 50800 0
Australia
Phone 50800 0
+61 7 3362 0222
Fax 50800 0
+61 7 3845 3637
Email 50800 0
j.mccarthy@uq.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary