Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Optimizing the dose of tafenoquine for the radical cure of Plasmodium vivax malaria in Southeast Asia

Award Number: U01AI165321
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/08/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

Group Awards By:

View Award Description

Optimizing the dose of tafenoquine for the radical cure of Plasmodium vivax malaria in Southeast Asia - PROJECT SUMMARY In East Asia and Oceania Plasmodium vivax is the most common cause of malaria. Relapses occur in over half the infections and comprise the main burden of P. vivax malaria. Relapses are the major cause of morbidity, particularly in children and pregnant women. In recent years targeted malaria elimination has driven down Plasmodium falciparum malaria in these populous regions, but P. vivax malaria has re-emerged rapidly because of relapse. Preventing relapse (radical cure) requires administration of an 8-aminoquinoline – which until recently meant a 7-14 day course of primaquine. Tafenoquine is a recently registered slowly eliminated 8- aminoquinoline with the substantial operational advantage of providing single dose radical cure. However, Phase 3 randomized controlled trials showed that the currently recommended 300mg adult dose (~ 5mg/kg) of tafenoquine had low radical curative efficacy against P. vivax malaria. Tafenoquine doses up to 14mg/kg have proved safe and well tolerated in adults and children with >70% G6PD activity. We obtained the individual participant (N= 1102) data from the Phase 3 pre-registration trials (DETECTIVE and GATHER; see Bibliography, references 22-24). Individual patient data meta-analysis (see Bibliography, reference 32) shows clearly that a) the dose response curve is steep around the currently recommended dose (5mg/kg) and b) the odds ratio for P. vivax recurrence (<4 months) is 0.69 (95% CI 0.64 to 0.75; p=10-21) for each mg/kg increase in dose. Thus, increasing the dose by half (i.e., to 7.5mg/kg) is predicted to result in an overall >90% reduction of P. vivax recurrence. To test this prediction, we propose conducting a multi-center double-blind randomized clinical trial in five countries in the Greater Mekong sub-Region. Aim 1 compares the radical curative efficacies of the current tafenoquine dose and a 50% higher dose (e.g., 300mg versus 450mg in persons ≥35kg) in adults and children with acute vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) activity >70%. Relapses will be distinguished from reinfections probabilistically based on parasite genotyping and time to event information. To detect very low-density P. vivax parasitemias which might be suppressed by tafenoquine, ultrasensitive polymerase chain reaction (uPCR) will be performed. Aim 2 assesses plasma, urine, and red blood cell tafenoquine concentrations and explores potential tafenoquine metabolites. Genotyping for CYP2D6 mutations and measurements of methemoglobinemia will be included as exposure correlates of radical curative efficacy. Aim 3 assesses safety and tolerability of the higher tafenoquine dose. Tolerability, gastrointestinal symptoms, hematocrit, and elevated blood methemoglobin concentrations will be monitored. This study will provide definitive evidence to guide tafenoquine dosing for the radical cure of P. vivax malaria. An efficacious, safe and well tolerated single dose anti-relapse therapeutic will substantially improve the treatment of P. vivax malaria and accelerate malaria elimination.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $468,894 )
2026	2025	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	002	3	3/10/2026	SUPPLEMENT FOR EXPANSION	-$117,395
2026	2025	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	000	3	1/27/2026	NON-COMPETING CONTINUATION	$468,894
2026	2025	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	001	3	3/10/2026	NON-COMPETING CONTINUATION	$0
2026	2025	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	003	3	3/13/2026	SUPPLEMENT FOR EXPANSION	$117,395
														Subtotal = $468,894

Issue Date FY: 2025 ( Subtotal = $1,005,855 )
2025	2025	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	000	3	9/17/2025	NON-COMPETING CONTINUATION	$888,460
2025	2025	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	001	3	9/18/2025	SUPPLEMENT FOR EXPANSION	$117,395
														Subtotal = $1,005,855

Issue Date FY: 2024 ( Subtotal = $1,045,386 )
2024	2024	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	000	2	8/23/2024	NON-COMPETING CONTINUATION	$1,045,386
														Subtotal = $1,045,386

Issue Date FY: 2023 ( Subtotal = $1,067,899 )
2023	2023	UNIVERSITY OF OXFORD	UNIVERSITY OFFICES	OXFORD				GBR	Allergy and Infectious Diseases Research	000	1	9/8/2023	NEW	$1,067,899
														Subtotal = $1,067,899

Grand Total All Awards = $3,588,034

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Optimizing the dose of tafenoquine for the radical cure of Plasmodium vivax malaria in Southeast Asia

Award Number: U01AI165321

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/08/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer