Southeast Asia Dose Optimization of Tafenoquine

NCT04704999 | Recruiting Phase 4 DMC

• 2 other identifiers: MAL2000521-0023
• Study Type: interventional
• Target: 700
• Locations: 4 countries
• Sites: 5

Brief Summary

Tafenoquine was recently approved by regulatory authorities in the USA and Australia. Tafenoquine is an alternative radical curative treatment to primaquine acting against the dormant liver stage of Plasmodium vivax (the hypnozoite). Tafenoquine (an 8-aminoquinoline) has the substantial advantage of single dosing as compared to a 14-day course of primaquine to achieve radical cure. The recommended tafenoquine dose is 300 mg, which was shown to be significantly worse in radical curative efficacy to a total primaquine dose of 3.5 mg/kg in Southeast Asia. The cure rate of tafenoquine 300 mg in Southeast Asian study sites was only 74%. The comparator 3.5 mg/kg total primaquine dose is the standard and most commonly used dose globally, but in Southeast Asia and the Western Pacific, higher doses of primaquine are needed for radical cure. This study aims to determine the optimal dose of tafenoquine in Southeast Asia.

Conditions

Plasmodium Vivax Malaria

Keywords

Plasmodium vivax; Relapse; 8-aminoquinoline; Tafenoquine; Radical cure; Drug efficacy; Adults; Pediatrics

Outcome Measures

Primary Outcomes (1)

• Microscopy positive P. vivax recurrence after radical treatment up to month 4

  At month 4

Secondary Outcomes (9)

• Sub-microscopic P. vivax recurrence after radical treatment between day 28 and month 4

  At Day 28; Month 4

• Sub-microscopic P. vivax recurrence with very low parasite density after radical cure treatment at days 14 and 21

  At Day 14 and 21

• Number of serious adverse events (e.g., hospitalization for symptomatic hemolysis or methemoglobinemia)

  At Days 1, 2, 7, 14 and Months 1, 2, 3, 4

• Number of adverse events (e.g., gastrointestinal symptoms)

  At Days 1, 2, 7, 14 and Months 1, 2, 3, 4

• Methemoglobin levels measured by pulse oximetry at day 7

  At Day 7

Study Arms (2)

Tafenoquine standard dose (TQ-current)

ACTIVE COMPARATOR

Arm 1 * \>10 kg to ≤20 kg 100 mg * \>20 kg kg ≤35 kg 200 mg * \>35 kg 300 mg Tafenoquine will be given as 100 mg coated tablets. Tablets will be given, and dosing will be based on weight bands.

Drug: Tafenoquine; Drug: Chloroquine; Drug: Artemether 20 mg-Lumefantrine 120 mg

Tafenoquine 50% higher dose (TQ-higher)

ACTIVE COMPARATOR

Arm 2 * \>10 kg to ≤20 kg 150 mg * \>20 kg kg ≤35 kg 300 mg * \>35 kg 450 mg Tafenoquine will be given as 100 mg coated tablets. Whole tablets will be given, and dosing will be based on weight bands.

Drug: Tafenoquine; Drug: Chloroquine; Drug: Artemether 20 mg-Lumefantrine 120 mg

Interventions

Tafenoquine DRUG

Tafenoquine will be given as 100mg coated tablets. Tablets will be given based on weight bands.

Tafenoquine 50% higher dose (TQ-higher); Tafenoquine standard dose (TQ-current)

Chloroquine DRUG

Chloroquine will be given as daily dose over 3 days (25mg/kg total dose divided 10/10/5mg/kg)

Tafenoquine 50% higher dose (TQ-higher); Tafenoquine standard dose (TQ-current)

Artemether 20 mg-Lumefantrine 120 mg DRUG

Artemether-lumefantrine will be given twice daily over 3 days. Whole tablets will be given based on weight bands.

Tafenoquine 50% higher dose (TQ-higher); Tafenoquine standard dose (TQ-current)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with symptomatic P. vivax mono-infection as diagnosed by microscopy
• Fever or history of fever in the previous 7 days
• Quantitative G6PD activity ≥70% of the population median
• Weight \>10 kg and ≥2 years old
• Ability to understand the study instructions and provide written informed consent.
• Willing to be followed for 4 months

You may not qualify if:

• Pregnancy
• Lactation
• Hb \< 8 g/dL
• Severe malaria
• Blood transfusion in the last 4 months
• History of allergic response to an 8-aminoquinoline or the nationally recommended schizonticide (e.g., chloroquine, artemether-lumefantrine)
• Any previous history of a haemolytic event Presence of any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study (e.g. chronic disease, medications that potentiate or inhibit CYP2D6 or CYP2C8 isoenzyme function)

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (5)

Mahidol Oxford Tropical Medicine Research Unit (MORU), Cambodia

Siem Reap, Cambodia

NOT YET RECRUITING

Lao Oxford Mahosot Hospital Wellcome Trust Research Unit (LOMWRU)

Vientiane, Laos

RECRUITING

Mahidol Vivax Research Unit (MVRU)

Bangkok, Thailand

NOT YET RECRUITING

Shoklo Malaria Research Unit (SMRU)

Bangkok, Thailand

NOT YET RECRUITING

Oxford University Clinical Research Unit (OUCRU)

Bình Phước, Vietnam

NOT YET RECRUITING

MeSH Terms

Conditions

Malaria, Vivax; Recurrence

Interventions

tafenoquine; Chloroquine; Artemether; Lumefantrine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Cindy Chu, MD, PhD

  Lao-Oxford-Mahosot Hospital-Wellcome Research Unit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cindy Chu, MD, PhD

CONTACT

+856 (0) 21 250 752; cindy@tropmedres.ac

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Single (Outcomes Assessor) This is a double-blind randomized superiority trial. The laboratory staff responsible for reading the malaria blood smear slides will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 12, 2021
• Study Start: July 22, 2024
• Primary Completion (Estimated): October 4, 2027
• Study Completion (Estimated): February 7, 2028
• Last Updated: March 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

LA (1); VN (1); CA (1); TH (2)