ACT vs CQ With Tafenoquine for P. Vivax Mono-infection

Summary

In this area of Greater Mekong Subregion (GMS), vivax malaria is the most common kind of malaria. It can stay very long in the liver, and come out later to make another episode of illness. This can happen many times even without a mosquito bite. Only 8-aminoquinoline drugs can kill the liver forms of the malaria parasite. One of these drugs is called primaquine, and it has been used all over the world for a long time. There is now a new formulation of this 8-aminoquinoline drug called tafenoquine that can also treat the malaria in the liver. The main benefit of this drug is that it is a single dose, which makes much convenient for the patients as well as for the malaria control program than conventional 14 days of primaquine. Recent research suggests that ACT (Artemisinin Combination Therapy) may antagonise the efficacy of tafenoquine (Baird et al. 2020 ASTMH Annual Meeting) . This could prevent the use of tafenoquine in areas with chloroquine resistant P. vivax parasites where national malaria programmes recommend ACTs for vivax malaria. Also, currently recommended tafenoquine dose is sub-optimal: 300 mg dose proved significantly inferior to low dose primaquine in a meta-analysis of the phase 3 studies when restricted to the Southeast Asian region (Llanos-Cuentas et al. 2019 NEJM; Watson et al. 2022a Elife). A tafenoquine dose of 450mg is predicted to provide \>90% of the maximal effect. The objective of this research is to find out whether 450 mg dose of tafenoquine can be combined effectively with ACT providing a short course treatment for P. vivax malaria.

Conditions

• Malaria
• Malaria, Vivax
• Plasmodium Vivax Malaria

Interventions

DRUG

Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose)

* Dihydroartemisinin-Piperaquine will be purchased as Duo-Cotecxin® Beijing Holley-Cotec Pharmaceuticals Co., Ltd, China). One tablet contains 40 mg of dihydroartemisinin and 320 mg piperaquine (i.e. a 1:8 ratio). A weight-based regimen containing a total dose of approximately 7 mg/kg DHA and 55 mg/kg piperaquine given in 3 divided doses once daily. * Tafenoquine KODATEF® 150 mg film-coated tablets will be purchased from Biocelect (Suite 5.02, Level 5, 139 Macquarie Street, Sydney NSW, 2000 Australia), 450 mg (4 1/2 tablets) will be given.

DRUG

Chloroquine plus Tafenoquine (450 mg adult dose)

* Chloroquine will be dosed as a 25 mg/kg base given in divided doses of 10 mg/kg orally on days 0 and 1, and in 5 mg/kg dose on day 2. Tablets will be obtained from Government Pharmaceutical Organization (GPO) in Bangkok, Thailand and supplied as 250 mg tablets (155.3 mg base). * Tafenoquine KODATEF® 150 mg film-coated tablets will be purchased from Biocelect (Suite 5.02, Level 5, 139 Macquarie Street, Sydney NSW, 2000 Australia), 450 mg (4 1/2 tablets) will be given.

DRUG

Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose)

* Artemether-Lumefantrine will be given at a standard dose of 20/120 mg twice daily for three days. (AL will be purchase from Novartis Pharma Services AG- Lichtstrasse 35, CH-4056 Basel, Switzerland.) * Tafenoquine KODATEF® 100 mg film-coated tablets will be purchased from Biocelect (Suite 5.02, Level 5, 139 Macquarie Street, Sydney NSW, 2000 Australia), 450 mg (4 1/2 tablets) will be given.

Sponsors & Collaborators

• Mahidol Oxford Tropical Medicine Research Unit

  collaborator OTHER

• University of Oxford

  collaborator OTHER

• Shoklo Malaria Research Unit

  lead OTHER

Principal Investigators

• Francois Nosten, Prof · Shoklo Malaria Research Unit

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-26

Primary Completion

2026-02-28

Completion

2026-08-31

Countries

• Thailand

Study Locations