Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001008718
Ethics application status
Approved
Date submitted
9/09/2013
Date registered
11/09/2013
Date last updated
15/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
An experimental study to investigate the transmission of malaria from a person infected with a specific species of malaria to mosquito feeding on that infected person’s blood
Scientific title
A Pilot Study To Assess Mosquito Transmissibility of Plasmodium vivax In Participants Inoculated intravenously with the parasite Isolate Hmpbs-Pv
Secondary ID [1] 283167 0
nil
Universal Trial Number (UTN)
nil
Trial acronym
Experimental Vivax Transmission to Anopheles (EVITA)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria Infection 290027 0
Condition category
Condition code
Infection 290406 290406 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in 3 cohorts, each with 2 participants. All participants will receive malaria inoculum injection of ~100 viable Plasmodium vivax-infected human erythrocytes administered intravenously. Participants will be monitored on an outpatient basis including with blood collection for quantification of parasitaemia by PCR, and for unexpected early onset of symptoms of malaria or adverse events until they are admitted to the inpatient facility for curative antimalarial chemotherapy.
On the three days up to the anticipated commencement day of treatment as determined by PCR, transmission studies will be undertaken. Over those 3 days blood will be collected twice daily from each participant for membrane feeding assays with An. Stephensi, and for PCR testing and exploratory research.

On the morning of those 3 days participants will then be placed in the insectary and asked to allow 30 vector mosquitoes to feed on the volar surface of their forearms or thighs for a period of 15 + 5 minutes (direct feeding assay).

On the day designated for commencement of treatment, as determined by the onset of clinical manifestations of malaria infection, participants will be admitted to the study unit and confined for safety monitoring and antimalarial treatment with the antimalarial drug Riamet (artemether20mg/lumefantrine120mg). This will be administered by oral administration of 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.

Following treatment, participants will be followed up as inpatients for 36 hours to ensure tolerance of therapy and clinical response. Once clinically well, they will be followed up on an outpatient basis for continued dosing of antimalarial drug, safety and clearance of malaria parasites as assessed by sensitive quantitative PCR. Follow up visits for safety assessments will be performed on day 28 after malaria challenge and participants are required to be contactable and available up to 2 weeks following this end of study visits.
Intervention code [1] 287897 0
Treatment: Drugs
Comparator / control treatment
NIL
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290430 0
To evaluate the P. vivax induced blood stage malaria (IBSM) model with subsequent experimental mosquito feeding as a system to study infectivity to vector mosquitoes.
Assessed by: mid gut dissection of mosquitoes and microscopic visualization, to evaluate the production of oocysts
Timepoint [1] 290430 0
Timepoint: 7-8 days after feeding
Primary outcome [2] 290431 0
To assess the safety of the P. vivax blood stage malaria (IBSM) model in healthy malaria-naive volunteers
Assessed by close monitoring of clinical status, including physical examination vital signs electrocardiograms (ECG) and by laboratory pathology testing, including hematology, chemistry, and serology.
Timepoint [2] 290431 0
Timepoint
Adverse event (such as fever fatigue, vomiting and diarrhea) screening through to Day 16, Day 28
Hematology, biochemistry : screening, Day 0,14 16 28
ECG and Serology: Screening and Day 28
Physical examination and vital signs: Screening, Day 0 and 7-28
Secondary outcome [1] 304505 0
To further characterize the parasite growth curves after I.V. inoculation of healthy participants with P. vivax blood stage parasites.
Assessed by: PCR testing of collected blood
Timepoint [1] 304505 0
Timepoint: Day 7-14
Secondary outcome [2] 304506 0
To further characterize the parasite clearance profiles by PCR after administration of antimalarial drug after inoculation with P. vivax blood stage parasites.
Assessed by: PCR testing of collected blood
Timepoint [2] 304506 0
Timepoint: Day 14-16, 28

Eligibility
Key inclusion criteria
1. Adults (males and non pregnant and non lactating females), aged between 18 and 50 years who do not live alone (from Day 0 until at least the end of the antimalarial drug treatment).
2. BMI within the range 18–30 kg/m2; weight greater than 50kg, with good peripheral venous access
3. Able and willing (in the Investigator’s opinion) to comply with all study requirements.
4. Non-smokers.
5. Female participants of childbearing potential must have adequate contraception in place.
6. Blood group A Duffy antigen positive.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of clinical malaria, or traveled to or lived (greater than 2 weeks) in a malaria-endemic country during the past 12 months.
2. Known severe reaction to mosquito bites other than local itching and redness.
3. Evidence of increased cardiovascular disease risk.
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. Have ever received a blood transfusion.

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
n/a
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As this is a pilot study no formal hypothesis testing will be undertaken for the clinical endpoints. Descriptive statistical analysis will be used. Growth and clearance of parasitemia will be compared to data on hand for analysis of mosquito transmission.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2013
Actual
8/10/2013
Date of last participant enrolment
Anticipated
1/04/2014
Actual
16/09/2014
Date of last data collection
Anticipated
Actual
5/11/2014
Sample size
Target
6
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 287921 0
Charities/Societies/Foundations
Name [1] 287921 0
Program for Appropriate Technology in Health (PATH)
Country [1] 287921 0
United States of America
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] 286649 0
None
Name [1] 286649 0
Address [1] 286649 0
Country [1] 286649 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289852 0
The Queensland Institute of Medical Research Human Research Ethics Committee
Ethics committee address [1] 289852 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Australia
Ethics committee country [1] 289852 0
Australia
Date submitted for ethics approval [1] 289852 0
Approval date [1] 289852 0
23/08/2013
Ethics approval number [1] 289852 0
P1549

Summary
Brief summary
A renewed focus on malaria elimination has increased the priority of research towards development of interventions to block malaria transmission, including transmission blocking vaccines (TBVs). This Phase I clinical trial is designed test if our established malaria challenge system is suitable to study transmission to mosquitoes. A Plasmodium vivax malaria infection will be established in 6 human volunteers. Vector transmission studies will be undertaken with a laboratory strain of Anopheles stephensi mosquitoes to assess the transmission of parasites to the mosquitoes, both by direct feeding on volunteers and by artificial membrane feeding. Assessment of infection of the mosquitos will be done by mid gut dissection and microscopic visualisation, to evaluate the production of oocysts following the feeding experiments. Once feeding experiments have been completed, participants will then commence curative anti malarial treatment.
Trial website
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 42770 0
Dr James McCarthy
Address 42770 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 42770 0
Australia
Phone 42770 0
+61 7 33620222
Fax 42770 0
+61 7 3845 3637
Email 42770 0
[email protected]
Contact person for public queries
Name 42771 0
Ms Silvana Sekuloski
Address 42771 0

QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 42771 0
Australia
Phone 42771 0
+61 7 38453856
Fax 42771 0
+61 7 38453507
Email 42771 0
[email protected]
Contact person for scientific queries
Name 42772 0
Dr James McCarthy
Address 42772 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 42772 0
Australia
Phone 42772 0
+61 7 33620222
Fax 42772 0
+61 7 3845 3637
Email 42772 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
EmbaseSafety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission.2016https://dx.doi.org/10.1371/journal.pntd.0005139
Dimensions AIPlasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+ T Cell Population with Cytotoxic Potential2016https://doi.org/10.1371/journal.pntd.0005031
N.B. These documents automatically identified may not have been verified by the study sponsor.