Investigating the Pharmacology of Tafenoquine in Papua New Guinean Children With Uncomplicated Malaria

Summary

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.

Conditions

• Uncomplicated Malaria

Interventions

DRUG

Single dose tafenoquine (10 mg/kg)

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.

DRUG

Dihydroartemisinin-piperaquine (DHA-PPQ)

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.

DRUG

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.

Sponsors & Collaborators

• Papua New Guinea Institute of Medical Research

  collaborator OTHER_GOV

• The University of Western Australia

  collaborator OTHER

• Curtin University

  lead OTHER

Principal Investigators

• Brioni R Moore, PhD · Curtin University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-30

Primary Completion

2026-12-31

Completion

2026-12-31

Countries

• Papua New Guinea

Study Locations