Tafenoquine Combinations for Improved Radical Cure Efficacy of Plasmodium Vivax

April 9, 2026 updated by: Walter Reed Army Institute of Research (WRAIR)

Evaluating Tafenoquine Combinations for Improved Radical Cure Efficacy of Plasmodium Vivax

This study is to conduct a clinical trial of tafenoquine combinations to compare the rates of therapeutic efficacy of dihydroartemisinin-piperaquine or artemether-lumefantrine with tafenoquine to chloroquine plus tafenoquine in preventing recurrence of Plasmodium vivax over a 6-month period in adult subjects with uncomplicated P. vivax infection living in Thailand.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background: There are several anti-malarials to kill P. vivax in the bloodstream and resolve the illness; however, the hallmark of P. vivax is its dormant liver-stage parasite (hypnozoite), which can reactivate months to years after the initial treatment, resulting in relapses of clinical disease. There are only two drugs that can clear hypnozoites, both of the 8-aminoquinoline (8-AQ) class: primaquine (PQ) and tafenoquine (TQ). The anti-hypnozoite mechanism(s) of action of these drugs are not entirely clear but presumably act by reactive oxygen species generated by redox cycling of the metabolites of PQ or TQ. In late 2020, a clinical trial in Indonesia (nicknamed INSPECTOR), testing TQ plus the blood stage drug, dihydroartemisinin-piperaquine (DHA-PPQ), reported 79% of participants experienced TQ drug failure which continued to have P. vivax relapses. This rate of relapse was almost the same as those participants who received no TQ (only DHA-PPQ). The dramatically lower efficacy was unexpected, the mechanisms behind these failures, unknown, and with TQ being one of the only two available medications to fully treat P. vivax infections, underscores the need to investigate the causes and find potential solutions. The best method to evaluate drug efficacy and the mechanisms underlying treatment failures is through a clinical trial. A Congressionally Directed Medical Research Program (CDMRP)-funded Clinical Trial Award project will conduct a clinical trial of tafenoquine in adults infected with P. vivax living in Thailand and fits the CDMRP Strategic Goal to develop and test more effective and shorter treatment regimens, including those that address treatment resistance. This study is supported by the U.S. DoD.

Study objective: The primary objective is to compare the rates of therapeutic efficacy of dihydroartemisinin-piperaquine or artemether-lumefantrine with tafenoquine to chloroquine plus tafenoquine in preventing recurrence of Plasmodium vivax over a 6-month period in adult subjects with uncomplicated P. vivax infection.

Study design: This clinical study designs a four arm, randomized, open-label clinical efficacy trial of adults with acute, uncomplicated mono-infection with P. vivax. At enrollment, participants will be randomized with ration 1:1:1:1.

  • Arm 1: TQ 300 mg once + Chloroquine (CQ),weight-based dosing (following Thai National Treatment guidelines), for the 3-day course.
  • Arm 2: TQ 300 mg once + Dihydroartemisinin-piperaquine (DHA-PPQ), weight-based dosing (following Thai National Treatment guidelines), for the 3-day course.
  • Arm 3: TQ 300 mg once + Artemether-Lumefantrine (AL), weight-based dosing twice daily for the 3-day course.
  • Arm 4: DHA-PPQ weight-based dosing (following Thai National Treatment guidelines), for the 3-day course. Then pause the treatment for one day and tafenoquine 300 mg will be given on the 4th day.

All study participants with P. vivax infection meeting inclusion/exclusion criteria will be enrolled, treated monitored for recurrence over 6 months to determine the rate of efficacy of the four groups. After 7 days inpatient, all participants will have outpatient clinic follow-up visits at Day 14, 21, 28, 60, 90, 120, 150 and 180. Arm 4 schedule will be different a bit depend on blood and urine collection schedule.

Study population: Adult subjects, aged 18 years or older, male or non-pregnant/non-lactating female who agreed not to be pregnant, who are diagnosed with uncomplicated P. vivax mono-infection.

Number of subjects: Up to 300 volunteers will be screened to meet the goal enrollment is 200 participants (50 in each arm) to meet the primary objective and endpoint of efficacy at 180 days.

Study location: Clinical study activities will take place in Tha Song Yang district, Tak province, in western Thailand, along the Thai-Myanmar border. Another site, Sop Moei District, Mae Hong Son province, may be added if enrollment is deemed insufficient to meet target goal of 200 enrolled cases within the sponsor's specified timeline.

Timeline: The clinical study itself is expected to run for approximately 5 years to enroll and complete study procedures for all subjects. Sample and data analysis would still be conducted after clinical study closure.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Thailand
    • Bangkok
      • Ratchathewi, Bangkok, Thailand, 10400
        • Tha Song Yang Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Krisada Jongsakul, MD
        • Sub-Investigator:
          • Eric Garges, MD
        • Sub-Investigator:
          • Krit Harncharoenkul, MD
        • Sub-Investigator:
          • Michele Spring, MD
        • Sub-Investigator:
          • Edgie-Mark Co, MD
        • Sub-Investigator:
          • Panupong Kowsurat, MD
        • Sub-Investigator:
          • Chanasorn Srichan, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants who meet all of the following criteria may participate in the study:

    • Thai or non-Thai, male or non-pregnant/non-lactating female, aged at least 18 years
    • Willingness to participate in the study and provides signed written informed consent form
    • Have P. vivax malaria mono-infection as determined by blood smear, with a parasitemia range of 100-400,000 parasites/microliter
    • Have normal (non-deficient or >70% activity) G6PD phenotype as measured by quantitative spectrophotometry
    • Agree to not seek outside medical care prior to contacting the WRAIR-AFRIMS study team if a fever develops during study participation (approximately 180 days), unless emergency medical care is required

Exclusion Criteria:

  • Participants meeting any of the following criteria will be excluded from this study:

    • Have an allergic reaction to any of the study drugs or components (AL,TQ, artemisinins, PPQ or CQ)
    • History of anti-malarial drug use within the past 14 days (28 days for mefloquine or PPQ)
    • On screening EKG, found to have a QTcF of greater than 450 milliseconds (ms) (470 ms for females)
    • History of sudden cardiac death in an immediate family member, or personal history of known symptomatic coronary artery disease or arrhythmias

    • Acute or chronic, clinically significant, pulmonary, cardiovascular, hepatic, neurologic, or renal functional abnormality, as determined by history, physical examination, and laboratory evaluation; specific tests for this criteria, and in the definition of severe malaria, include:

      • Hemoglobin level of <7 g/dL
      • Alanine aminotransferase (ALT/SGPT) and/or Aspartate transaminase (AST/SGOT) more than two times upper limit of normal or total bilirubin greater than 3 mg/dL
      • Serum creatinine greater than 3 mg/dL
    • History of or current psychotic disorders (schizophrenia or other type of psychosis with hallucinations/delusions)
    • Have symptoms of severe malaria needing urgent treatment, such as impaired consciousness, shock, seizures, respiratory distress, unable to eat or drink, prostration (WHO guidelines for malaria, 2024) or other signs/symptoms of concern to the doctors
    • Are a pregnant or lactating female, or female of childbearing age, up to 50 years of age or otherwise individually assessed for childbearing potential, who does not agree to use an acceptable form of contraception (e.g. pills or injectable) during this study and for 1 month after study completion
    • Chronic use of medications that may cause drug interactions with tafenoquine (metformin) and/or drugs known to prolong the QTc interval.
    • Any other significant finding that in the opinion of the study physician would increase the risk of having an adverse outcome from participating in this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: TQ+CQ Arm
TQ 300 mg once + Chloroquine (CQ), weight-based dosing for 3 days course
Drug: Tafenoquine (TQ)
Tafenoquine 150 mg
Other Names:
  • KRINTAFEL
Drug: Chloroquine (CQ)
Chloroquine 150 mg base
Active Comparator: TQ+DHA-PPQ Arm
TQ 300 mg once + Dihydroartemisinin-piperaquine (DHA-PPQ), weight-based dosing for 3 days course
Drug: Tafenoquine (TQ)
Tafenoquine 150 mg
Other Names:
  • KRINTAFEL
Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)
It is 40 mg DHA/320 mg PPQ
Other Names:
  • Eurartesim
Active Comparator: TQ+AL Arm
TQ 300 mg once + Artemether-Lumefantrine (AL), weight-based dosing twice daily for the 3-day course
Drug: Tafenoquine (TQ)
Tafenoquine 150 mg
Other Names:
  • KRINTAFEL
Drug: Artemether-lumefantrine (AL)
It is 20 mg of artemether and 120 mg lumefantrine
Other Names:
  • Coartem
Active Comparator: DHA-PPQ + delayed TQ Arm
DHA-PPQ weight-based dosing for the 3-day course, then pause the treatment for one day and tafenoquine 300 mg once on the 4th day.
Drug: Tafenoquine (TQ)
Tafenoquine 150 mg
Other Names:
  • KRINTAFEL
Drug: Dihydroartemisinin-piperaquine (DHA-PPQ)
It is 40 mg DHA/320 mg PPQ
Other Names:
  • Eurartesim

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Estimate the rate of recurrence in all participants with uncomplicated P. vivax mono-infection in the 6 months following treatment with chloroquine, CQ, artemether-lumefantrine, AL, or dihydroartemisinin-piperaquine, DHA-PPQ, paired with tafenoquine, TQ
Time Frame: From enrollment to 6 months follow up
After discharge from hospital, outpatient follow-up visits will be scheduled at Day 14, 18 (Arm 4), 21, 25 (Arm 4), 28, 32 (Arm 4), 60, 90, 120, 150 and 180 to monitor for P. vivax recurrences.
From enrollment to 6 months follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Walter Reed Army Institute of Research (WRAIR)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Brian Vesely, PhD, Walter Reed Army Institute of Research-Armed Forces Research Institute of Medical Sciences (WRAIR-AFRIMS), Thailand

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 9, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WRAIR#3297
  • CDMRPL-24-0-PR241374 (Other Grant/Funding Number: CDMRP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD data sets will not be shared as it's confidentiality of participants

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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