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Trial registered on ANZCTR


Registration number
ACTRN12620000995976
Ethics application status
Approved
Date submitted
20/01/2020
Date registered
6/10/2020
Date last updated
30/10/2020
Date data sharing statement initially provided
6/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Blood stage antimalarial activity of tafenoquine in healthy subjects infected with Plasmodium falciparum
Scientific title
A phase 1b study to evaluate the blood stage antimalarial activity of a single oral dose of tafenoquine in healthy subjects experimentally infected with Plasmodium falciparum
Secondary ID [1] 300312 0
CTM1901 (Sponsor: QIMR Berghofer Medical Research Institute)
Universal Trial Number (UTN)
n/a
Trial acronym
n/a
Linked study record
n/a

Health condition
Health condition(s) or problem(s) studied:
Malaria 315916 0
Condition category
Condition code
Infection 314188 314188 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-centre, open-label phase 1b study using the P. falciparum induced blood stage malaria (IBSM) model to evaluate the antimalarial activity of a single oral dose of tafenoquine in healthy subjects. The study will be conducted in up to three parts.

Part 1:
Part 1 will evaluate the activity of different single oral doses of tafenoquine administered after intravenous inoculation with blood stage P. falciparum in clearing parasites. Subjects will be intravenously inoculated with approx. 2,800 viable P. falciparum parasite-infected human erythrocytes on Day 0. Subjects will be admitted to the clinical trial site for single-dose administration of tafenoquine on Day 8. Subjects in Cohort 1 will be administered a single oral dose of 300 mg tafenoquine. Participants are observed during tafenoquine administration and mouth checks performed.
The Safety and Data Review Team (SDRT) will review safety, tolerability and parasitaemia data up to and including Day 10 to determine if parasitaemia is safely and effectively cleared at this dose level and decide on the dose to be administered to Cohort 2. A similar procedure will be followed to select the dose to be administered to Cohorts 3 and 4. Screening for these subsequent cohorts can commence once the SDRT have made a decision regarding the previous cohort. The SDRT will review data up to and including Day 10. Thus it is likely that screening for subsequent cohorts will begin at a minimum of 14 days after the previous cohort commences. The maximum single dose of tafenoquine administered in the study will not exceed 600 mg, and the minimum dose will be no less than 25 mg. All subjects will receive compulsory antimalarial rescue treatment with artemether/lumefantrine (six doses of four tablets administered orally over three consecutive days) on Day 48±2, or earlier in the event that tafenoquine treatment fails to clear asexual parasitaemia. If gametocytes are present at or after the time of treatment with artemether/lumefantrine, 45 mg primaquine may be administered as a single oral dose at the Investigator’s discretion. If an allergy or contraindication to artemether/lumefantrine develops, then atovaquone/proguanil will be administered. If subjects are unable to complete oral antimalarial rescue treatment, they will receive intravenous artesunate

The SDRT will review safety, tolerability and parasitaemia data up to and including Day 10 of Cohort 2 to determine if parasitaemia is safely and effectively cleared at the dose level chosen for Cohort 2 and decide on the dose to be administered to Cohort 3.
The SDRT will review safety, tolerability and parasitaemia data up to and including Day 10 of Cohort 3 to determine if parasitaemia is safely and effectively cleared at the dose level chosen for Cohort 3 and decide on the dose to be administered to Cohort 4.
If parasitaemia is safely and effectively cleared at the dose level chosen for the previous cohort, then it is likely that the SDRT may choose a lower dose for the subsequent cohort. The minimum single dose of tafenoquine administered in this study will be no less than 25 mg. If parasitaemia is not safely and effectively cleared at the dose level chosen for the previous cohort, then the SDRT may choose a higher dose for the subsequent cohort. The maximum single dose of tafenoquine administered in the study will not exceed 600 mg.

Part 2:
The decision to commence part 2 occur after safety review and submission to the funding sponsor the Bill and Melinda Gates Foundation, as additional funding will be required to proceed with Parts 2 and 3.
Part 2 of the study is optional, and is dependent on the results obtained in Part 1. Part 2 will be composed of up to two cohorts of up to eight subjects per cohort, and will evaluate the potential of a single oral dose of tafenoquine administered prior to intravenous inoculation with blood stage P. falciparum to protect against infection.
Subjects will be randomised on Day 0 to receive either a single oral dose of tafenoquine (active group) or no tafenoquine (control group) in a 7:1 ratio (active: control). No blinding will be performed. All subjects will be intravenously inoculated with ~ 2,800 viable P. falciparum parasite-infected human erythrocytes on Day 3. Subjects will then be followed up as outpatients at least three times per week for safety assessments and blood sampling to monitor parasitaemia and blood and plasma concentrations of tafenoquine up to Day 35±2.
In the event that parasitaemia reaches =10,000 parasites/mL, antimalarial rescue treatment with artemether/lumefantrine will be initiated. Artemether/lumefantrine treatment may also be initiated before parasitaemia reaches this threshold at Investigator’s discretion in the interest of subject safety. All subjects will receive compulsory antimalarial rescue treatment with artemether/lumefantrine on Day 32±2 if not given earlier.
If gametocytes are present at or after the time of treatment with artemether/lumefantrine, 45 mg primaquine may be administered as a single oral dose at Investigator’s discretion. If an allergy or contraindication to artemether/lumefantrine develops, then atovaquone/proguanil will be administered. If subjects are unable to complete oral antimalarial rescue treatment, they will receive intravenous artesunate. The dose of tafenoquine administered to the active group in Part 2 will be the lowest dose that was found to safely and effectively clear parasites in Part 1 of the study. The SDRT will meet between the two proposed cohorts in Part 2 to review safety, tolerability and parasitaemia data from the first cohort. If the dose chosen in cohort 1 part 2, safely protects against infection, then a second cohort may occur with the same dose as used in cohort 1 (to achieve statistical power). If the dose chosen in cohort 1 part 2, does not safely protect against infection, then a second cohort may not occur.




Part 3:
Part 3 of the study is optional, and is dependent on the results obtained in Part 1. Subjects will be inoculated with P. falciparum and monitored up to approximately Day 8 as described above for part 1. On approximately Day 8 (or earlier if one of the criteria listed above for part 1 occur), subjects will be administered a low dose of piperaquine (480 mg). Subjects will return to the clinic on Day 9 and Day 10 to ensure adequate clinical and parasitological response to treatment. It is expected that a single 480 mg dose of piperaquine will be insufficient to prevent recrudescence, thus an additional dose of piperaquine (960 mg) will be administered on Day 10. The purpose of this piperaquine treatment regimen is to clear asexual parasites (responsible for clinical symptoms) and prevent recrudescence, while allowing transmissible gametocytes to develop. Between Day 11 and Day 23, regular outpatient visits will occur to monitor parasitaemia and gametocytaemia, and perform safety assessments and blood sampling to determine piperaquine exposure by measuring blood and plasma piperaquine concentrations.
On Day 24, the transmission of gametocytes to Anopheles mosquitoes will be assessed using an enriched membrane feeding assay (eMFA). Subjects will then be randomised to receive either a single oral dose of tafenoquine (active group) or no tafenoquine (control group) in a 7:1 ratio (active: control). No blinding will be performed. Additional eMFAs will be performed on Days 25, 28 and 31 to determine the effect of tafenoquine on transmission. Blood and plasma concentrations of tafenoquine and its 5, 6-orthoquinoine metabolite will be measured to monitor tafenoquine exposure.
All subjects will begin compulsory antimalarial rescue treatment with artemether/lumefantrine following the eMFA on Day 31, or earlier in the event that piperaquine treatment fails to clear asexual parasitaemia or prevent recrudescence. Artemether/lumefantrine treatment may also be initiated at any time at the Investigator’s discretion in the interest of subject safety. If gametocytes are present at or after the time of treatment with artemether/lumefantrine, 45 mg primaquine may be administered as a single oral dose at Investigator’s discretion. If an allergy or contraindication to artemether/lumefantrine develops, then atovaquone/proguanil will be administered. If subjects are unable to complete oral antimalarial rescue treatment, they will receive intravenous artesunate. The end of study visit will occur on Day 34±2.
The dose of tafenoquine administered to the active group in Part 3 will be the lowest dose that was found to safely and effectively clear parasites in Part 1 of the study. The SDRT will meet between the two proposed cohorts in Part 3 to review safety, tolerability, parasitaemia, gametocytaemia, and transmission data from the first cohort.
Intervention code [1] 316585 0
Treatment: Drugs
Comparator / control treatment
Dose comparison- reference dose is 300mg
Control group
Dose comparison

Outcomes
Primary outcome [1] 322563 0
The incidence of asexual parasitaemia clearance without treatment failure up to Day 48 plus or minus 2 in subjects within a dose cohort in Part 1.Clearance and Treatment failure will be assessed using qPCR with data linkage to clinical assessment.
Timepoint [1] 322563 0
Malaria 18S quantitative PCR (qPCR): prior to tafenoquine treatment and at 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 66, 72, 84, and 96 hours post tafenoquine treatment. qPCR will then be performed during follow up visits up to Day 48 plus or minus 2.
Secondary outcome [1] 378948 0
The absence of significant parasitaemia (less than 1,000 parasites/mL) in subjects in Part 2 up to Day 32 plus or minus 2 (29 plus or minus 2 days post-inoculation).
Timepoint [1] 378948 0
Malaria 18S qPCR (Part 2): at least three times per week post malaria parasite inoculation (Day 3) up to Day 32 plus or minus 2.
Secondary outcome [2] 378949 0
Whole blood and plasma samples will be assessed for (PK) parameters for each dose cohort calculated using non-compartmental methods: AUClast, AUCinf, Cmax, tmax, t1/2, CL/F, Vd/F and Lambda.
Timepoint [2] 378949 0
PK timepoints (Part 1): prior to tafenoquine treatment and at 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 66, 72, 84, and 96 hours post tafenoquine treatment. PK samples will then be collected at least once weekly at the Investigator’s discretion.
PK timepoints (Part 2): prior to tafenoquine treatment, daily for three days, and then at least once weekly at the Investigator’s discretion.
Secondary outcome [3] 378950 0
The parasite reduction ratio per 48 hours (log10PRR48) and corresponding parasite clearance half-life of each dose cohort. This is a composite outcome.
Timepoint [3] 378950 0
Malaria 18S qPCR timepoints (Part 1): prior to tafenoquine treatment and at 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 66, 72, 84, and 96 hours post tafenoquine treatment.
Secondary outcome [4] 378951 0
Malaria 18S qPCR (whole blood) and PK samples (plasma) will be used to assess the following parameters estimated using PK/PD modelling: Emax, EC50, MIC, and MPC90.
Timepoint [4] 378951 0
Malaria 18S qPCR and PK samples collected from the start of the study until the End of Study. PK timepoints (Part 1): prior to tafenoquine treatment and at 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 66, 72, 84, and 96 hours post tafenoquine treatment. PK samples will then be collected at least once weekly at the Investigator’s discretion Malaria 18S qPCR timepoints (Part 1): prior to tafenoquine treatment and at 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 66, 72, 84, 96, 108 and 120 hours post tafenoquine treatment and then at least three times weekly until compulsory antimalarial rescue treatment
Secondary outcome [5] 378953 0
To assess the safety and tolerability of different single oral doses of tafenoquine. Participants will be asked about any adverse events they experience at every outpatient visit. All clinically significant out of range laboratory parameters, physical assessment and vital signs will be captured as adverse events. Participants will be provided with diary cards to capture self-reported adverse events. Reported adverse events include, but are not limited to, headache, diarrhoea, dizziness, nausea, psychiatric disorders (anxiety, insomnia, and abnormal dreams), decreased haemoglobin, increased blood methaemoglobin, and eye disorders (including vortex keratopathy).
Timepoint [5] 378953 0
Adverse event recording: At all timepoints up to 41 plus or minus 2 days after tafenoquine administration in Part 1, 32 plus or minus 2 days after tafenoquine administration in Part 2 and 31 plus or minus 2 days after tafenoquine administration in Part 3.

Eligibility
Key inclusion criteria
1. Male or female (non-pregnant, non-lactating) aged 18 to 55 years inclusive who will be contactable and available for the duration of the study and up to two weeks following the End of Study visit.
2. Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive).
3. Certified as healthy by a comprehensive clinical assessment (detailed medical history, complete physical examination and special investigations).
4. At least normal G6PD enzyme activity levels as defined by the parameters of the specific quantitative G6PD test employed.
5. Vital signs at screening and pre-inoculation (measured after five minutes in the supine position):
• Systolic blood pressure (SBP) - 90-140 mmHg,
• Diastolic blood pressure (DBP) - 40-90 mmHg,
• Heart rate (HR) 40-100 bpm.
6. Electrocardiograph (ECG) ranges at screening and pre-inoculation: QTcB/QTcF less than or equal to 450 ms for male subjects, QTcB/QTcF less than or equal to 470 ms for female subjects, and PR interval less than or equal to 210 ms.
7. Female subjects of childbearing potential who have, or may have, male sexual partner(s) during the course of the study should be using an insertable (implant and IUD, injectable, transdermal or combination oral contraceptive approved by the TGA combined with a barrier contraceptive from the time of informed consent through to 11 days after inoculation with the malaria challenge agent. Abstinent female subjects must agree to start a double method if they start a sexual relationship with a male during the study. Adequate contraception does not apply to subjects of childbearing potential with same sex partners (abstinence from penile-vaginal intercourse), when this is their preferred and usual lifestyle. Female subjects must not be planning in vitro fertilisation within the required contraception period.
Women of non-childbearing potential who will not require contraception during the study are defined as: surgically sterile (tubal ligation is not considered surgically sterile), post-menopausal (spontaneous amenorrhoea for greater than or equal to 12 months, or spontaneous amenorrhoea for 6-12 months and follicle-stimulating hormone (FSH) greater than or equal to 40 IU/mL; either should be together with the absence of oral contraceptive use for greater than 12 months).

Male subjects who have, or may have, female sexual partner(s) during the course of the study must agree to use a double method of contraception including condom plus diaphragm, or condom plus insertable device, or condom plus stable oral/transdermal/injectable hormonal contraceptive by the female partner, from the time of informed consent through to 90 days after the last dose of tafenoquine. Abstinent male subjects must agree to start a double method if they begin sexual relationships with a female during the study, and through to 90 days after the last dose of tafenoquine. Male subjects with female partners that are surgically sterile, or male subjects who have undergone sterilisation and have had testing to confirm the success of the sterilisation may also be included.
8. Completion of the written informed consent process prior to undertaking any study-related procedure.
9. Must be willing and able to communicate and participate in the whole study.
10. Agreement to adhere to Lifestyle Considerations throughout study duration.

Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subject lives alone (at any stage from inoculation day until the end of the artemether/lumefantrine treatment).
2. Any history of malaria or participation in a previous malaria challenge study or malaria vaccine study.
3. Must not have travelled to or lived (GREATER THAN 2 weeks) in a malaria-endemic region during the past 12 months or planned travel to a malaria-endemic region during the course of the study. Must not have lived for greater than 1 year in a malaria-endemic region in the past 10 years. Must not have ever lived in a malaria-endemic region for more than 10 years inclusive. For endemic regions see https://map.ox.ac.uk/country-profiles/#!/. Bali is not considered a malaria-endemic region.
4. Has evidence of increased cardiovascular disease risk (defined as greater than 10 percent, 5-year risk for those greater than 35 years of age, as determined by the Australian Absolute Cardiovascular Disease Risk Calculator (http://www.cvdcheck.org.au/)). Risk factors include sex, age, systolic blood pressure (mm/Hg), smoking status, total and HDL cholesterol (mmol/L), and reported diabetes status.
5. History of splenectomy.
6. Subject unwilling to defer blood donations to the Blood Service for at least six months after the EOS visit.
7. Subject who has ever received a blood transfusion.
8. Any recent (less than 6 weeks) or current systemic therapy with an antibiotic or drug with potential antimalarial activity (e.g. chloroquine, piperaquine phosphate, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, doxycycline etc.).
9. Known hypersensitivity to artesunate or any of its excipients, artemether or other artemisinin derivatives, proguanil/atovaquone, primaquine, or 4-aminoquinolines.


10. Haematology, clinical chemistry or urinalysis results at screening or at the Day -1 to Day -3 eligibility visit that are outside of Sponsor-approved clinically acceptable laboratory ranges, and/or are considered clinically significant by the Investigator.
11. Participation in any investigational product study within the 12 weeks preceding inoculation in Part 1, or IMP administration in Part 2.
12. Symptomatic postural hypotension at screening (confirmed on two consecutive readings), irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure greater than or equal to 20 mmHg within 2-3 minutes when changing from supine to standing position.
13. History or presence of diagnosed (by an allergist/immunologist) or treated (by a physician) food or known drug allergies (including but not limited to allergy to any of the antimalarial rescue treatments), or any history of anaphylaxis or other severe allergic reactions including face, mouth, or throat swelling or any difficulty breathing. Subjects with seasonal allergies/hay fever or allergy to animals or house dust mite that are untreated and asymptomatic at the time of dosing can be enrolled in the study.
14. History of convulsion (including intravenous drug or vaccine-induced episodes). A medical history of a single febrile convulsion during childhood is not an exclusion criterion.
15. Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immuno-deficiencies), insulin-dependent and non-insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, porphyria, psoriasis, rheumatoid arthritis, asthma (excluding childhood asthma, or mild asthma with preventative asthma medication required less than monthly), epilepsy, or obsessive-compulsive disorder.
16. History of malignancy of any organ system (other than localised basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within five years of screening, regardless of whether there is evidence of local recurrence or metastases.
17. Subjects with history of schizophrenia, bi-polar disease, psychoses, disorders requiring lithium, attempted or planned suicide, or any other severe (disabling) chronic psychiatric diagnosis.
18. Subjects who have received psychiatric medications within one year prior to enrolment, or who have been hospitalised within five years prior to enrolment for either a psychiatric illness or due to danger to self or others.



19. History of an episode of minor depression that required at least six months of pharmacological therapy and/or psychotherapy within the last five years; or any episode of major depression.
The Beck Depression Inventory will be used as an objective tool for the assessment of depression at screening. In addition to the conditions listed above, subjects with a score of 20 or more on the Beck Depression Inventory and/or a response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) will not be eligible for participation. These subjects will be referred to a general practitioner or medical specialist as appropriate. Subjects with a Beck score of 17 to 19 may be enrolled at the discretion of the Investigator if they do not have a history of the psychiatric conditions mentioned in this criterion and their mental state is not considered to pose additional risk to the health of the subject or to the execution of the study and interpretation of the data gathered.
20. History of recurrent headache (e.g. tension-type, cluster or migraine) with a frequency of greater than or equal to 2 episodes per month on average and severe enough to require medical therapy, during the 5 years preceding screening.
21. Presence of clinically significant infectious disease or fever (e.g. sublingual temperature greater than or equal to 38.5°C) within the five days prior to Inoculation in Part 1, or IMP administration in Part 2.
22. Evidence of acute illness within the four weeks prior to screening that the Investigator deems may compromise subject safety.
23. Significant inter-current 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.


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
Part 1 is a single group. In part 2 and 3 each cohort there have a a single control participant. A randomisation schedule will be used for their allocation. This will occur prior to investigation product administration.
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A total of up to 60 malaria-naïve, healthy males or females will be enrolled in this study. Up to 28 subjects in Part 1, up 16 subjects in Parts 2 and 3. The study will be conducted in three parts.
Part 1 will evaluate the activity of different single oral doses of tafenoquine administered after intravenous inoculation with blood stage P. falciparum in clearing parasites. Each cohort will be composed of up to eight subjects, and if no subjects in the cohort fail to clear asexual parasites, there is 80 percent confidence that the true failure rate does not exceed 20 percent, or 95 percent confidence that the true failure rate does not exceed 32 percent (based on a one-sided exact confidence interval).
Previous PK/PD modelling and preliminary physiological based pharmacokinetic (PBPK) simulations of tafenoquine suggest that a single 300 mg oral dose will effectively clear blood stage P. falciparum in the IBSM model. As such, Cohort 1 of Part 1 will evaluate the safety, tolerability and parasite clearance potential of a 300 mg dose of tafenoquine. This first cohort will be composed of four rather than eight subjects, as it is not designed to address the primary objective or to compare clearance with other cohorts. Instead the purpose of this first cohort is to confirm the suggestion that a single 300 mg oral dose will effectively clear blood stage P. falciparum in the IBSM model.

Part 2 will evaluate the potential of a single oral dose of tafenoquine administered prior to intravenous inoculation with blood stage P. falciparum to protect against infection. If tafenoquine provides fully effective prophylaxis, then probability models will be used to estimate the maximum failure rate in future populations. If tafenoquine provides only partially effective prophylaxis, then response will be measured against a reference standard for parasite multiplication rate (PMR) derived from other studies conducted at QIMR Berghofer, as well as delay in qPCR patency and reduced peak parasitaemia. The required sample sizes are 14 subjects with no parasitaemia to demonstrate prophylaxis, and eight subjects with no parasitaemia to demonstrate at least 60 percent efficient prophylaxis with steady state tafenoquine. Hence, Part 2 will be composed of up 16 subjects divided in up to two cohorts.
Continuous variables will be summarised with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. Categorical variables will be summarised with the number of observations and the numbers and percent from each category.

Part 3 will evaluate if a single oral dose of tafenoquine is active against mature gametocytes, and is able to block transmission to mosquitoes. Sample size calculations for part 3 are based on determining transmission inhibition at Day 25 given that individuals were infectious at Day 24 and the assumption of a 75% infectivity rate for eMFAs at baseline. With a total of 14 subjects randomised to tafenoquine treatment there will be 10 tafenoquine dosed subjects infective at Day 24 (lower bound of 95% confidence interval is 41.9%). Of those 10 subjects infective at Day 24, assuming a 95% transmission blocking efficacy for tafenoquine treatment, and all 10 subjects inhibit transmission, then the lower bound of the 95% confidence interval for the reduction in mosquito infectivity will be 69.2%. Hence, Part 3 is planned to be composed of up 16 subjects divided in up to two cohorts, with 14 subjects randomised to receive tafenoquine. Two subjects (one in each cohort) will not be administered tafenoquine and will act as controls to demonstrate transmission viability.

Recruitment
Recruitment status
Recruiting
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 hospital [1] 17454 0
University of Sunshine Coast Health Clinics - Sippy Downs
Recruitment postcode(s) [1] 31078 0
4506 - Morayfield
Recruitment postcode(s) [2] 31182 0
4556 - Sippy Downs

Funding & Sponsors
Funding source category [1] 304733 0
Charities/Societies/Foundations
Name [1] 304733 0
Bill and Melinda Gates Foundation
Address [1] 304733 0
500 Fifth Avenue North, Seattle, WA 98109
Country [1] 304733 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Road, Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 305048 0
None
Name [1] 305048 0
Address [1] 305048 0
Country [1] 305048 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305158 0
QIMR Berghofer Human Research Ethics Committee
Ethics committee address [1] 305158 0
300 Herston Road, Herston QLD 4006
Ethics committee country [1] 305158 0
Australia
Date submitted for ethics approval [1] 305158 0
25/08/2020
Approval date [1] 305158 0
07/10/2020
Ethics approval number [1] 305158 0
P3646

Summary
Brief summary
This is a single-centre, open-label phase 1b study using the P. falciparum induced blood stage malaria (IBSM) model to evaluate the antimalarial activity of a single oral dose of tafenoquine in healthy subjects. The study will be conducted in three parts.
Part 1 will be composed of an initial cohort of four subjects followed by up to three cohorts of up to eight subjects per cohort, and will evaluate the potential of different single oral doses of tafenoquine to clear asexual blood stage P. falciparum parasites and inhibit the development of the sexual stage of the parasite (gametocyte) responsible for transmission to mosquitoes.
Part 2 will be composed of up to two cohorts of up to eight subjects per cohort, and will evaluate the potential of a single oral dose of tafenoquine administered prior to intravenous inoculation with blood stage P. falciparum to protect against infection.
Part 3 will be composed of up to two cohorts of up to eight subjects per cohort and will determine if a single oral dose of tafenoquine is active against mature gametocytes, and is able to block transmission to mosquitoes.
Parts 2 and 3 of the study are optional and are dependent on the results obtained in Part 1.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99434 0
A/Prof Bridget Barber
Address 99434 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd,
Herston QLD 4006
Country 99434 0
Australia
Phone 99434 0
+61733620498
Fax 99434 0
Email 99434 0
bridget.barber@qimrberghofer.edu.au
Contact person for public queries
Name 99435 0
Dr Rebecca Webster
Address 99435 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd,
Herston QLD 4006
Country 99435 0
Australia
Phone 99435 0
+61 7 33620167
Fax 99435 0
Email 99435 0
rebecca.webster@qimrberghofer.edu.au
Contact person for scientific queries
Name 99436 0
A/Prof Bridget Barber
Address 99436 0
QIMR Berghofer Medical Research Institute, 300 Herston Rd,
Herston QLD 4006
Country 99436 0
Australia
Phone 99436 0
+61733620498
Fax 99436 0
Email 99436 0
bridget.barber@qimrberghofer.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results