A Phase 4 interventional study of Single dose tafenoquine (10 mg/kg) and Dihydroartemisinin-piperaquine (DHA-PPQ) in Uncomplicated Malaria, sponsored by Curtin University. Not yet recruiting at 1 site in Papua New Guinea. Open to participants aged 2 Years to 12 Years. Per ClinicalTrials.gov, last updated 2026-02-12.
Sponsored by Curtin University · Phase 4, Interventional, and Treatment
Plasmodium vivax is the most geographically widespread malaria species and the second largest contributor to symptomatic malaria worldwide. It accounts for half of all malaria cases outside Africa, with an estimated 14.3 million clinical vivax malaria cases reported annually, contributing to an annual cost of US$359 million. Children are most vulnerable to infection, with P. vivax prevalence peaking between 2 to 6 years of age. In Papua New Guinea (PNG), there are >1.5 million suspected P. vivax cases annually, and while P. falciparum infections are the most prevalent, P. vivax transmission is the most intense in the world. P. vivax in PNG provides a unique epidemiological setting in which to assess innovative treatments in children.The complex biology of P. vivax represents a challenge for malaria control and chemotherapy, especially dormant liver-stage parasites (hypnozoites) which can reactivate (relapse) and cause disease at a time remote from the primary infection. Hypnozoite relapse is the primary cause of vivax malaria in endemic regions and is resistant to most antimalarial drugs. Identifying effective treatments for radical cure, the complete elimination of parasites (both blood- and liver-stage), is therefore a priority. The World Health Organization (WHO) recommends a 14-day radical cure regimen for uncomplicated vivax malaria; comprised of blood stage treatment (chloroquine or artemisinin combination therapy (ACT)) and 14 days of the 8-aminoquinoline drug primaquine (PQ; 0.25-0.5 mg/kg/day) for liver-stage cure. More recently, the 8-aminoquinoline tafenoquine has garnered interest as an alternative radical cure agent to primaquine. However, there is limited data on the pharmacokinetics, tolerability and radical cure efficacy of tafenoquine in children. Furthermore, early data suggest a drug interaction between TQ and artemisinin combination therapy (ACT) drugs - which requires further investigation and confirmation. This study will generate critical paediatric safety, tolerability, pharmacokinetic, and preliminary efficacy data for TQ when administered with either artemether-lumefantrine or dihydroartemisinin-piperaquine in PNG children with uncomplicated malaria.
This is an open-label study to evaluate the safety, tolerability, pharmacokinetic disposition and preliminary efficacy of tafenoquine, when co-administered as part of a radical cure regimen with two artemisinin combination therapies in Papua New Guinean children with uncomplicated malaria. This study represents the second part of a multi-phase investigation of tafenoquine in PNG children (Study 1: NCT07052162). In this study, children aged 2 to 12 years will be eligible for inclusion in the study providing they have uncomplicated malaria (P. falciparum and/or P. vivax malaria; confirmed by rapid diagnostic test and/or microscopy), normal G6PD activity (>70% enzyme activity by SD Biosensor), no evidence of severe malaria, no significant comorbidity, and no history of previous hypersensitivity to 8-aminoquinolines, artemether-lumefantrine or dihydroartemisinin-piperaquine. All participants will be admitted to the Alexishafen Health Centre for the first 24-hours of the study, to facilitate blood sampling and clinical monitoring. After admission, baseline demographic and medical history will be taken, and the participants will undergo a full clinical assessment to establish baseline safety indices. The 60 participants will then be randomized 1:1 to receive either i) single-dose TQ as 10 mg/kg given with the first dose of artemether-lumefantrine treatment regimen (Coartem®; ARM 1.7 mg/kg and LUM 10 mg/kg, twice daily for 3 days) with water and a low-fat meal (unless indicated otherwise in Study 1), or ii) single-dose TQ as 10 mg/kg given with the first dose of dihydroartemisinin-piperaquine (Eurartesim®; DHA 2.5 mg/kg and PQ phosphate 20 mg/kg, once daily for 3 days) with water and a low-fat meal (unless indicated otherwise in Study 1). For pharmacokinetic analysis, each participant will be allocated a randomised sampling schedule with dried blood spots for pharmacokinetic analysis performed at 6 of 15 time points (2, 4, 8, 12, 18, 24, 38 and 48 hours, Days 3, 4, 7, 14, 28, 42 and 56). At each allocated time point, 0.5 mL samples will be collected by finger-prick with five 50 µL blood drops spotted on to Whatman Protein 903 cards for dried blood spot analysis. The remaining blood will be collected into lithium heparin anticoagulant. Both dried blood spot and plasma samples will be collected at all time points for pharmacokinetic analyses. Standardised review, including adverse-effect questionnaires, and clinical monitoring (haemoglobin, methaemoglobin, reticulocyte counts, malaria blood films) will be conducted at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). Safety testing (hepatorenal function tests (ALT, total bilirubin, creatinine), haemoglobin, urine dipstick analysis and electrocardiogram trace, will be taken at 4, 24 hours and on Days 3, 7 and 28.
The primary aim of the study is to characterise the pharmacokinetic profile of TQ (and its primary metabolite) in PNG children.
Secondary objectives include;
The investigators hypothesise that:
123 studies on the registry are indexed under Malaria, Vivax; 19 are open to participants now.
This study's planned enrollment of 60 is below the median of 150 across 103 interventional studies indexed under Malaria, Vivax.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Single-dose tafenoquine as 10 mg/kg given with the first dose of artemether-lumefantrine treatment regimen (ARM 1.7 mg/kg and LUM 10 mg/kg, twice daily for 3 days) with water and a low-fat meal
Drug: Single dose tafenoquine (10 mg/kg) · Drug: Artemether + Lumefantrine
Single-dose tafenoquine as 10 mg/kg given with the first dose of dihydroartemisinin-piperaquine (DHA 2.5 mg/kg and PQ phosphate 20 mg/kg, once daily for 3 days) with water and a low-fat meal
Drug: Single dose tafenoquine (10 mg/kg) · Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)
Drug page: Tafenoquine
Participants will receive single-dose TQ as 10 mg/kg given with the first dose of ACT. Food (low-fat meal) is taken to attenuate any gastrointestinal adverse effects that are related to taking TQ on an empty stomach. Combinations of full or half-tablets will be swallowed whole or crushed lightly (tablets) or dissolved in boiled water (if dispersible tablets are available), as directly observed treatment. Children vomiting within the first 30 minutes of treatment will be withdrawn, and will receive the remaining treatment course of their randomized ACT as for PNG Standard Treatment Guidelines.
Also known as: Tafenoquine succinate, TQ, Kodatef
Drug pages: Artenimol · Piperaquine
Participants will receive dihydroartemisinin-piperaquine (DHA 2.5 mg/kg and PQ phosphate 20 mg/kg), once daily for 3 days with water and a low-fat meal. Combinations of full or half-tablets will be swallowed whole or crushed lightly (tablets) or dissolved in boiled water (if dispersible tablets are available), as directly observed treatment.
Also known as: DP, DHA-PPQ, Eurartesim
Drug pages: Artemether · Lumefantrine
Participants will receive artemether-lumefantrine (ARM 1.7 mg/kg and LUM 10 mg/kg) twice daily for 3 days with water and a low-fat meal. Combinations of full or half-tablets will be swallowed whole or crushed lightly (tablets) or dissolved in boiled water (if dispersible tablets are available). Morning doses will be observed as directly observed treatment, with evening doses dispensed to the parent/guardian each day. Parents will be asked to report approximate time of evening dosing the following morning, and return any pills that were not successfully administered.
Also known as: ARM-LUM, Mala1, Coartem
Pharmacokinetic: Tafenoquine terminal elimination half-life
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Pharmacokinetic: Tafenoquine distribution half-life
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Pharmacokinetic: Tafenoquine absorption half-life
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Pharmacokinetics: Tafenoquine clearance
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Pharmacokinetics: Tafenoquine volume of distribution
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Pharmacokinetic: Tafenoquine maximal concentration
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Pharmacokinetics: Tafenoquine area under concentration-time curve
Pharmacokinetic parameters of tafenoquine and 5,6-orthoquinone tafenoquine, will be ascertained using a nonlinear mixed-effects modelling approach (NONMEM), based on drug concentrations determined from blood samples collected at baseline (Day 0) and 6 of 13 randomized collection time points (2, 4, 8, 12, 24 and 48 hours and Days 3, 4, 7, 14, 28, 42 and 56.
Time frame: 56-days after tafenoquine administration
Safety: Change in haemoglobin over 84 days
A fingerprick blood sample will be drawn at baseline to determine pre-treatment haemoglobin concentration (point-of-care HemoCue Hb201+, Radiometer, Australia). To monitor for post-treatment haemolysis, fingerprick haemoglobin samples will be taken at safety time points (4 and 24 hours, and on days 3, 7 and 28 post tafenoquine dosing) and all standardised review time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84).
Time frame: 84-days from tafenoquine administration
Safety: Change in methaemoglobin over 28 days
Methaemoglobin will be assessed by a Rad57 pulse oximeter with SpMet function (Masimo, USA) at all defined safety time points (4 and 24 hours) and standardised review time points (Days 0, 1, 2, 3, 4, 7, 14, and 28).
Time frame: 28-days from drug administration.
Safety: Change in hepatorenal function over 28 days
Hepatorenal function (creatinine, total bilirubin and alanine transaminase \[ALT\]) will be analysed on a Fuji Dri-Chem NX500 analyser (Fujifilm, Japan). 100 µL fingerprick blood samples will be collected at baseline, 4 and 24 hours, and on Days 3, 7 and 28 after tafenoquine dosing.
Time frame: 28-days from tafenoquine administration
Safety: Change in rate corrected QTc over 28 days
A 12-lead electrocardiogram will be conducted at baseline, 4 and 24 hours, and on Days 3, 7 and 28 after tafenoquine dosing to determine change in rate corrected QTc.
Time frame: 28-days from tafenoquine administration
Efficacy: PCR adjusted Day-28 P. vivax relapse efficacy
Blood smears for malarial microscopy and dried blood spots for molecular parasitology will be carried out at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). All blood films for malarial microscopy will be examined by two skilled microscopists blinded to treatment. Slides discrepant for positivity/negativity, speciation or parasitaemia (\>3x difference) will be adjudicated by a senior microscopist. Quantitative multi-species PCR will be assayed (using validated methods) on all collected samples to confirm outcomes from malarial microscopy, and report PCR adjusted relapse efficacy.
Time frame: 28-days from tafenoquine administration
Efficacy: PCR adjusted Day-42 P. vivax relapse efficacy
Blood smears for malarial microscopy and dried blood spots for molecular parasitology will be carried out at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). All blood films for malarial microscopy will be examined by two skilled microscopists blinded to treatment. Slides discrepant for positivity/negativity, speciation or parasitaemia (\>3x difference) will be adjudicated by a senior microscopist. Quantitative multi-species PCR will be assayed (using validated methods) on all collected samples to confirm outcomes from malarial microscopy, and report PCR adjusted relapse efficacy.
Time frame: 42-days from tafenoquine administration
Efficacy: PCR adjusted Day-84 P. vivax relapse efficacy
Blood smears for malarial microscopy and dried blood spots for molecular parasitology will be carried out at all daily follow-up time points (Days 0, 1, 2, 3, 4, 7, 14, 28, 42, 56 and 84). All blood films for malarial microscopy will be examined by two skilled microscopists blinded to treatment. Slides discrepant for positivity/negativity, speciation or parasitaemia (\>3x difference) will be adjudicated by a senior microscopist. Quantitative multi-species PCR will be assayed (using validated methods) on all collected samples to confirm outcomes from malarial microscopy, and report PCR adjusted relapse efficacy.
Time frame: 84-days after tafenoquine administration
Plan to share: No — Data may be shared upon contact with the principal investigators and approval by the PNG Institute of Medical Research. This process will be conducted on a case by case basis, as per agreements between collaborative partners.
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