Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001085561
Ethics application status
Approved
Date submitted
2/10/2015
Date registered
15/10/2015
Date last updated
25/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study in humans for purified Plasmodium falciparum 7G8 malaria parasites attenuated with Tafuramycin-A.
Scientific title
A pilot study in humans for purified Plasmodium falciparum 7G8 parasites attenuated with Tafuramycin-A.
Secondary ID [1] 287577 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 296387 0
Condition category
Condition code
Infection 296659 296659 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Volunteers will be inoculated on Day 0 of the study with purified human red blood cells infected with Plasmodium falciparum 7G8 and attenuated with Tafuramycin-A. Two different groups will be compared.

Group A: 3 x 10^7 purified Plasmodium falciparum 7G8 infected red blood cells attenuated with 200nM of Tafuramycin-A, administered intravenously.
Group B: 3 x 10^7 purified Plasmodium falciparum 7G8 infected red blood cells attenuated with 400nM of Tafuramycin-A, administered intravenously.

Duration of inoculum: one dose on Day 0.

Participants will be actively monitored up to Day 28 post injection and parasite levels in the blood will be monitored during this time period.

At Day 28, scheduled anti-malarial drug treatment (Riamet, also known as Artemether-Lumefantrine) will be administered. If however, there is evidence of a developing malaria infection prior to Day 28 (ie indicating attenuation of the parasites was incomplete), then participants will immediately commence anti-malarial treatment with Riamet.

Duration and dosage of anti-malarial treatment: Artemether (20mg) and Lumefantrine (120mg); 4 tablets orally as a single dose under direct supervision by clinical staff at the following times: 0, 8hrs, 24hrs, 36hrs, 47hrs and 60hrs making a total dose of 24 tablets in 6 doses.
Intervention code [1] 292990 0
Prevention
Intervention code [2] 292991 0
Treatment: Drugs
Comparator / control treatment
Volunteers will be inoculated on Day 0 of the study with purified human red blood cells infected with Plasmodium falciparum 7G8 and attenuated with Tafuramycin-A. Two different groups will be compared.

Group A: 3 x 10^7 purified Plasmodium falciparum 7G8 infected red blood cells attenuated with 200nM of Tafuramycin-A, administered intravenously.
Group B: 3 x 10^7 purified Plasmodium falciparum 7G8 infected red blood cells attenuated with 400nM of Tafuramycin-A, administered intravenously.
Control group
Dose comparison

Outcomes
Primary outcome [1] 296269 0
Parasite levels in the blood will be assessed by a sensitive molecular detection method (quantitative PCR) and microscopy to confirm the dose of Tafuramycin-A required to completely attenuate the P. falciparum 7G8 blood stage parasites.
Timepoint [1] 296269 0
Active monitoring of parasite levels in the blood every 2 days from Day 2-Day 28 post administration of attenuated P. falciparum 7G8 infected red blood cells.
Primary outcome [2] 296271 0
To characterise the safety and tolerability in humans of purified P. falciparum 7G8 blood stage parasites attenuated with Tafuramycin-A
Timepoint [2] 296271 0
Active monitoring daily from inoculation (ie Day 0) until Day 28. The final visit on day 90. Passive monitoring (ie participants contacting and reporting any potential adverse events to study staff outside of scheduled visits) from Day 0 to Day 90
Primary outcome [3] 296272 0
To characterise the immunogenicity of purified P. falciparum 7G8 blood stage parasites attenuated with Tafuramycin-A.

This will be assessed by implementing different immunological assays including flow cytometry and ELISAs
Timepoint [3] 296272 0
Compare antibody and T cell responses at day 0 with responses at Day 8, Day 14, Day 28 and Day 90.
Secondary outcome [1] 318017 0
To characterise the persistence in the peripheral blood of purified Plasmodium falciparum 7G8 blood stage parasites attenuated with Tafuramycin-A

Parasite levels in the blood will be assessed by a sensitive molecular detection method (quantitative PCR) and microscopy
Timepoint [1] 318017 0
From Day 2-Day 28 post administration of attenuated P. falciparum 7G8 infected red blood cells

Eligibility
Key inclusion criteria
1. Volunteers will be males, aged 18-50 years of age who do not live alone for the duration of the study.
2. Volunteers must have a BMI within the range of 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 their study schedule (maximum of 3 months)
5. Volunteers must be non-smokers or smoke equal to or less than 5 cigarettes/day and in good health, as assessed during pre-study medical examination and by review of screening results
6. Good peripheral venous access
Minimum age
18 Years
Maximum age
50 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has increased cardiovascular disease risk (defined as greater than 10%, 5 yr risk) as determined by the method of Gaziano et al 2008. Risk factors include: sex, age, systolic blood pressure, smoking status, body mass index (BMI, kg per mm^2), and reported diabetes status and blood pressure.
2. History of splenectomy
3. History of severe allergic reaction, anaphylaxis or convulsion following any vaccination, infusion or treatment with anti-malarial drugs artemether and/or lumefantrine.
4. Presence of current or suspected 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, obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.
5. Known inherited genetic anomaly (known as cytogenic disorders) eg Down’s syndrome.
6. Individuals wishing to donate blood to the Australian Red Cross Blood Service during the study or within 12 months of administration of the malaria inoculum.
7. The volunteer has a diagnosis of schizophrenia, bi-polar disease, severe depression or other severe (disabling) chronic psychiatric disorder. Participants who are receiving a single anti-depressant 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.
8. Has been hospitalised in the past 5 years prior to enrolment for psychiatric illness, history of suicide attempt or confinement for danger to self or others.
9. Known pre-existing prolongation of the QTc interval. Family history of congenital prolongation of the QTc interval on electrocardiograms or of sudden death or any other clinical conditions known to prolong the QTc interval eg volunteers with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
10. Recent or current therapy with antibiotic or drug with potential antimalarial activity (tetracycline, azithromycin, clindamycin, hydroxychloroquine etc).
11. Concomitant use of any drug which is metabolized by the cytochrome enzyme CYP2D6 (eg flecainide, metoprolol, imipramine, amitriptyline, clomipramine) OR drugs that are known to prolong the QTc interval e.g. antiarrhythmics of classes IA and III, neuroleptics, antidepressant agents, certain antibiotics (including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents), certain non-sedating antihistamines (terfenadine, astemizole), cisapride.
12. Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. Currently receiving or have previously received immunosuppressive therapy, including systemic steroids including ACTH or inhaled steroids in dosages which are associated with hypothalamic-pituitary axis suppression such as 1mg/kg/day or prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 micrograms per day or fluticasone 750 micrograms).
13. Presence of acute infectious disease or fever (e.g. sub-lingual temperature greater than or equal to 38.5oC) within the five days prior to the study product administration.
14. Evidence of acute illness within the 4 weeks before trial prior to screening and enrollment.
15. 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.
16. Alcohol consumption greater than community norms (ie more than 21 standard drinks per week for males).
17. A history of drug habituation, or any prior intravenous usage of an illicit substance.
18. Medical requirement for intravenous administration of immunoglobulin or blood transfusions.
19. Participation in any investigational product study within 8 weeks preceding the study.
20. 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 study.
21. Have ever received a blood transfusion.
22. Positive test for HIV, Hepatitis B, Hepatitis C, Human T-cell Lymphotropic Virus I and II(HTLV I and II), TB or syphilis.
23. Any clinically significant biochemical or haematologic abnormality (Hb must be greater than or equal to 13.5g/dL).
24. Ingestion of any poppy seeds within the 48 hours prior to the screening blood test (volunteers will be advised by phone not to consume any poppy seeds in this time period).
25. Detection of any specified drugs (as outlined in the study protocol) in the urine drug screen unless there is an explanation acceptable to the medical investigator (eg the subject has stated in advance that they consumed a prescription or OTC product which contained the detected drug) and/or the subject has a negative drug screen on retest by the pathology laboratory.
26. 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
27. G-6-PD deficiency
28. History of malaria
29. Travelled to or lived (>2 weeks) in a malaria-endemic country during the past 12 months or planned to travel to a malaria-endemic country during the course of the study.

Study design
Purpose of the study
Prevention
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
Phase
Phase 0
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2015
Actual
Date of last participant enrolment
Anticipated
5/01/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
6
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 292155 0
Government body
Name [1] 292155 0
NHMRC
Country [1] 292155 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
c/- Chris Davis
Griffith University, Gold Coast Campus
Institute for Glycomics, Building G26
Parklands Drive
Southport 4215
QLD
Country
Australia
Secondary sponsor category [1] 290829 0
None
Name [1] 290829 0
Not applicable
Address [1] 290829 0
Not applicable
Country [1] 290829 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293630 0
Griffith University Human Research Ethics Committee
Ethics committee address [1] 293630 0
Ethics committee country [1] 293630 0
Australia
Date submitted for ethics approval [1] 293630 0
17/09/2015
Approval date [1] 293630 0
26/10/2015
Ethics approval number [1] 293630 0
2015/686
Ethics committee name [2] 293916 0
Gold Coast Hospital and Health Service Human Research Ethics Committee
Ethics committee address [2] 293916 0
Ethics committee country [2] 293916 0
Australia
Date submitted for ethics approval [2] 293916 0
13/11/2015
Approval date [2] 293916 0
Ethics approval number [2] 293916 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 648 648 0 0
/AnzctrAttachments/369417-GU HREC Full Research Ethics Clearance 2015_686 (provisional to full approval).pdf

Contacts
Principal investigator
Name 60726 0
Prof Michael Good
Address 60726 0
c/- Griffith University, Gold Coast Campus, Institute for Glycomics, Building G26, Parklands Drive, Southport, 4215, QLD
Country 60726 0
Australia
Phone 60726 0
61 7 555 29435
Fax 60726 0
61 7 555 28098
Email 60726 0
[email protected]
Contact person for public queries
Name 60727 0
Danielle Stanisic
Address 60727 0
c/- Griffith University, Gold Coast Campus, Institute for Glycomics, Building G26, Parklands Drive, Southport, 4215, QLD
Country 60727 0
Australia
Phone 60727 0
61 7 555 28051
Fax 60727 0
61 7 555 28098
Email 60727 0
[email protected]
Contact person for scientific queries
Name 60728 0
Danielle Stanisic
Address 60728 0
c/- Griffith University, Gold Coast Campus, Institute for Glycomics, Building G26, Parklands Drive, Southport, 4215, QLD
Country 60728 0
Australia
Phone 60728 0
61 7 555 28051
Fax 60728 0
61 7 555 28098
Email 60728 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
No additional documents have been identified.