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

NCT05788094 | Recruiting Phase 4 DMC

• 1 other identifier: SMRU-01/23
• Study Type: interventional
• Target: 606
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

artemisinin combination treatment; tafenoquine; Plasmodium vivax malaria; Malaria

Outcome Measures

Primary Outcomes (1)

• Determine whether ACTs (Artemether-Lumefantrine or dihydroartemisinin-piperaquine (DHA-PPQ)) plus TQ is non-inferior to CQ plus TQ

  Number of participants with relapse-free efficacy (measured by PCR) in three arms

  Month-4

Secondary Outcomes (3)

• Characterise the safety and tolerability of three regimens

  Day3, Day7, Month1, Month2, Month3, Month4

• Characterise population pharmacokinetics of tafenoquine in three treatments

  Day3, Day7, Month1, Month2, Month3, Month4

• Met-Haemoglobin level a vivo pharmacodynamic proxy of oxidative antimalarial activity of tafenoquine

  Day3, Day7

Other Outcomes (2)

• Genotyping and probabilistic assessment to differentiate P. vivax relapse from reinfection

  Day3, Day7, Month1, Month2, Month3, Month4

• Evaluate the performance of village health workers as safe prescribers of tafenoquine radical cure

  Day3, Day7, Month1, Month2, Month3, Month4

Study Arms (3)

Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose)

EXPERIMENTAL

* 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® 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.

Drug: Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose)

Chloroquine plus Tafenoquine (450 mg adult dose)

EXPERIMENTAL

* 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® 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.

Drug: Chloroquine plus Tafenoquine (450 mg adult dose)

Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose)

EXPERIMENTAL

* 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.

Drug: Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose)

Interventions

Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose) DRUG

* 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.

Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose)

Chloroquine plus Tafenoquine (450 mg adult dose) DRUG

* 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.

Chloroquine plus Tafenoquine (450 mg adult dose)

Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose) DRUG

* 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.

Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with P. vivax mono-infection as diagnosed by Rapid Diagnostic Test
• Fever or history of fever in the previous 7 days
• Quantitative G6PD activity ≥70% of the population median i.e., ≥6.1U/gHb
• Age \> 18 years, Weight \>35 kg
• Ability to understand the study instructions and provide informed consent
• Willing to be followed for 4 months and likely to adhere to the study protocol.

You may not qualify if:

• Coincident P. falciparum malaria or other infections
• Pregnancy
• Lactation
• Hb \< 8 g/dL
• Quantitative G6PD activity \<70% of the population median i.e., \<6.1U/gHb
• Severe malaria (as per WHO guideline)
• History of allergic or haemolytic response to any of the study drugs

Sponsors & Collaborators

• Shoklo Malaria Research Unit: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator
• University of Oxford: collaborator

Study Sites (1)

Shoklo Malaria Research Unit (SMRU)

Mae Sot, Changwat Tak, 63110, Thailand

RECRUITING

MeSH Terms

Conditions

Malaria; Malaria, Vivax

Interventions

tafenoquine; Chloroquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Francois Nosten, Prof

  Shoklo Malaria Research Unit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aung Pyae Phyo, DPhil

CONTACT

+66 927 127 091; aungpyaephyo@tropmedres.ac

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Aung Pyae Phyo, Associate Research Fellow

Model Details: Randomised open label non-inferiority trial

Study Record Dates

• First Submitted: January 9, 2023
• First Posted: March 28, 2023
• Study Start: June 26, 2023
• Primary Completion: February 28, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 16, 2025

Record last verified: 2025-05

Locations

TH (1)