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Trial registered on ANZCTR


Registration number
ACTRN12612001096842
Ethics application status
Approved
Date submitted
9/10/2012
Date registered
15/10/2012
Date last updated
10/03/2014
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 HMPBS-Pv in humans (QP12C14)
Scientific title
An experimental study to characterize the in vivo safety and infectivity of the Plasmodium vivax isolate HMPBS-Pv in humans (QP12C14)
Secondary ID [1] 281276 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 287472 0
Condition category
Condition code
Infection 287805 287805 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I clinical trial to study the safety and infectivity of the Plasmodium vivax isolate by experimental inoculation with blood stage parasites in healthy volunteers. The dose will be 1800 Plasmodium vivax parasites administered as a single intravenous infusion.
Intervention code [1] 285745 0
Treatment: Other
Comparator / control treatment
No treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288028 0
To determine the safety of an experimental malaria challenge using naturally occurring parasites. This outcome will be assessed by measuring clinical and laboratory safety parameters.Clinical safety will be assessed by soliciting symptoms and signs of malaria and of adverse effects of the inoculum. Laboratory safety parameters will include standard haematologic and biochemical tests as well as serologic evidnece of seroconversion to adventitious agents.Solicited adverse events will include immediate allergic/hypersensitivity reactions to the inoculum as well as evidence of unexpected infection with adventitious agents
Timepoint [1] 288028 0
90 days
Primary outcome [2] 288029 0
To characterize the in vivo infectivity of P. vivax isolate HMPBS-Pv in healthy volunteers following infection with blood stage parasites. This outcome will be assessed by measuring the levels of P. vivax deoxyribonucleic acid (DNA) by quantitative real time polymerase chain reaction (qPCR).
Timepoint [2] 288029 0
14 days
Secondary outcome [1] 299304 0
To define the parasite growth curves after I.V. inoculation of healthy volunteers with naturally acquired P. vivax blood stage parasites This outcome will be assessed by correlation with blood smear data.
Timepoint [1] 299304 0
14 days
Secondary outcome [2] 299305 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.
This outcome will be assessed by measuring the levels of P. vivax deoxyribonucleic acid (DNA) by quantitative real time polymerase chain reaction (qPCR).
Timepoint [2] 299305 0
14 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. Adequate contraception to be in place for female and male volunteers and for females to have negative results on a serum or urine pregnancy test done before administration of study medication
7. Good peripheral venous access.
8. Blood group A.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) History of malaria.
2) Travelled to or lived for more than 2 weeks 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 percent, 5 year risk) as determined by the method of Gaziano et al. Risk factors include sex, age, systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/mm2), reported diabetes status and blood pressure
4) History of splenectomy.
5) Pregnant or breast feeding (all women will have a negative pregnancy test result prior to each study product administered).
6) History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.
7)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.
8) Known inherited genetic anomaly (known as cytogenetic disorders) e.g., Down’s syndrome
9) Volunteers unwilling to defer blood donations to the ARCBS for 6 months.
10) 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 enrolment without decompensating may be allowed to enrol in the study at the investigator’s discretion.
11) Presence of acute infectious disease or fever (e.g., sub-lingual temperature greater than or equal to 38.5 degrees Celcius) within the five days prior to study product administration).
12) Evidence of acute illness within the four weeks before trial prior to screening.
13) 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.
14) Have ever received a blood transfusion.
15) 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
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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)

Funding & Sponsors
Funding source category [1] 286039 0
Self funded/Unfunded
Name [1] 286039 0
Dr James McCarthy
Address [1] 286039 0
300 Herston Rd
Herston QLD 4029
Country [1] 286039 0
Australia
Primary sponsor type
Other
Name
The Queensland Institute of Medical Research
Address
300 Herston Rd
Herston QLD 4029
Country
Australia
Secondary sponsor category [1] 284853 0
None
Name [1] 284853 0
Address [1] 284853 0
Country [1] 284853 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288086 0
Queensland Institute of Medical Research Human Research Ethics Committee
Ethics committee address [1] 288086 0
The Queensland Institute of Medical Research
QIMR Locked Bag 2000
Royal Brisbane,QLD, 4029
Ethics committee country [1] 288086 0
Australia
Date submitted for ethics approval [1] 288086 0
30/08/2012
Approval date [1] 288086 0
09/10/2012
Ethics approval number [1] 288086 0
P1478

Summary
Brief summary
This is a pilot study of safety and infectivity in 2 healthy volunteers of a new Plasmodium vivax Malaria bank obtained from a malaria infected patient under HREC approval from both Royal Brisbane and Women’s Hospital and Queensland Institute of Medical Research. The Malaria bank was prepared under highly controlled conditions using protocols developed in conjunction with the Red Cross the US FDA and QGen. The clinical protocol is based on prior studies using the 3D7 Plasmodium falciparum isolate. The malaria bank has had full serological and PCR evaluations over 6 months meeting the criteria of ARCBS blood donation requirements. The antimalarial agent used to treat the malaria is the TGA approved Riamet, which was also used to eradicated the malaria infection in the patient donor.
Trial website
Trial related presentations / publications
James S. McCarthy, Paul M. Griffin, Silvana Sekuloski, A. Taylor Bright, Rebecca Rockett, David Looke, Suzanne Elliott, David Whiley, Theo Sloots, Elizabeth A. Winzeler, and Katherine R. Trenholme. "Experimentally Induced Blood-Stage Plasmodium vivax Infection in Healthy Volunteers." Journal of Infectious Disease 208.10 (2013): 1688-1694.
Public notes

Contacts
Principal investigator
Name 34742 0
Dr James McCarthy
Address 34742 0
Queensland Institute of Medical Research 300 Herston Rd Herston QLD 4006
Country 34742 0
Australia
Phone 34742 0
+61 7 33620222
Fax 34742 0
Email 34742 0
j.mccarthy@uq.edu.au
Contact person for public queries
Name 17989 0
Dr Silvana Sekuloski
Address 17989 0
Queensland Institute of Medical Research
300 Herston Rd
Herston QLD 4006
Country 17989 0
Australia
Phone 17989 0
+61 7 38453856
Fax 17989 0
+61 7 38453507
Email 17989 0
Silvana.Sekuloski@qimr.edu.au
Contact person for scientific queries
Name 8917 0
Dr Dr James McCarthy
Address 8917 0
Queensland Institute of Medical Research
300 Herston Rd
Herston QLD 4006
Country 8917 0
Australia
Phone 8917 0
+61 7 33620222
Fax 8917 0
+61 7 3845 3637
Email 8917 0
j.mccarthy@uq.edu.au

No information has been provided regarding IPD availability
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