A Revised Tafenoquine Dose to Improve Radical Cure for Vivax Malaria (TADORE)

A Revised Tafenoquine Dose to Improve Radical Cure for Vivax Malaria - TAfenoquine DOsing REvised

The goal of this clinical trial is to assess the efficacy and safety or a revised weight band tafenoquine dose in vivax malaria patients. The main question[s] it aims to answer are:

• is a revised weight-based TQ regimen (TQRevised: target dose 7.5mg/kg) non-inferior to high dose primaquine (7mg/kg over 7 days)
• is a revised weight-based TQ regimen (TQRevised: target dose 7.5mg/kg) superior to fixed dose tafenoquine (300mg)
• is the tolerability and safety of TQRevised acceptable
• is TQRevised acceptable and feasible Participants will receive a tafenoquine target dose 7.5mg/kg in weight bands. Researchers will compare this to patients receiving a fixed dose tafenoquine and high dose primaquine to see if safe and effective.

Study Overview

• Status: Not yet recruiting
• Conditions: Vivax Malaria
• Intervention / Treatment: Drug: Tafenoquine; Drug: Primaquine

• Study Type: Interventional
• Enrollment (Estimated): 1090
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hellen Mnjala; Phone Number: +610889468675; Email: hellen.mnjala@menzies.edu.au
• Study Contact Backup: Name: kamala K Thriemer; Phone Number: +610889468644; Email: kamala.ley-thriemer@menzies.edu.au

Study Locations

• Brazil
  • Manaus, Brazil
    • Dr Marcus Lacerda
• Ethiopia
  • Arba Minch, Ethiopia
    • Arba Minch General Hospital
    • Contact: Tamiru Shibiru Degaga, MD
• Indonesia
  • Timika, Indonesia
    • Dr Rini Poespoprodjo
• Papua New Guinea
  • Alexishafen, Papua New Guinea
    • Dr Moses Laman and Dr Brioni Moore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• P. vivax peripheral parasitaemia (mono-infection)
• G6PD normal status (G6PD activity ≥70% of the adjusted male median as determined by the Standard G6PD (SDBioline, ROK))
• Fever (temperature ≥37.5⁰C) or history of fever in the preceding 48 hours
• Written informed consent
• Living in the study area and willing to be followed for six months

Exclusion Criteria:

• Danger signs or symptoms of severe malaria
• Anaemia (defined as Hb <8g/dl)
• Pregnant or lactating females
• Regular use of drugs with haemolytic potential
• Known hypersensitivity to any of the study drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQRevised; Patients are treated with schizontocidal treatment plus a single weight-based oral dose of TQ (target dose 7.5mg/kg)	Drug: Tafenoquine; oral treatment
Active Comparator: TQStandard; Patients are treated with schizontocidal treatment plus single fixed oral dose of 300mg TQ (TQStandard)	Drug: Tafenoquine; oral treatment
Experimental: PQ7; Patients are treated with schizontocidal treatment plus oral high dose PQ (total dose 7 mg/kg) over 7 days (PQ7)	Drug: Primaquine; oral treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence risk of vivax parasitaemia	The incidence risk (time to first event) of any P. vivax parasitaemia during the 4-month follow up period as determined by microscopy.; compared between TQRevised and the PQ7 (non-inferiority); compared between TQRevised and TQStandard (superiority)	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence risk of vivax parasitaemia	The incidence risk (time to first event) of any P. vivax parasitaemia during the 4-month follow up period as determined by microscopy compared between TQStandard and PQ7	4 months
The incidence risk of symptomatic vivax parasitaemia	The incidence risk (time to first event) of symptomatic P. vivax parasitaemia during the 4 months follow up period as determined by microscopy	4 months
The incidence risk of vivax parasitaemia	The incidence risk (time to first event) of any P. vivax parasitaemia at 6-month follow up as determined by microscopy	6 months
The incidence risk of symptomatic vivax parasitaemia	The incidence risk (time to first event) of symptomatic P. vivax parasitaemia at 6-month follow up as determined by microscopy	6 months
The incidence rate of vivax parasitaemia	The incidence rate (events per person-time) of any P. vivax parasitaemia during the 6 months follow up period as determined by microscopy	6 months
The incidence rate of symptomatic vivax parasitaemia	The incidence rate (events per person-time) of symptomatic P. vivax parasitaemia during the 6 months follow up period as determined by microscopy	6 months
The incidence risk of anaemia	The incidence risk of developing severe anaemia (Hb < 5g/dl) or moderate (5g/dl and <7g/dl) anaemia within 7 and 14 days of starting treatment and/or requiring blood transfusion within the 6 months follow up period	7 and 14 days, 6 months
The incidence risk of an acute drop in Hb	The incidence risk of an acute drop in Hb of >25% to <7g/dl within 7 and 14 days of starting treatment	7 and 14 days
Adverse events	The number and proportion of adverse and serious adverse events in each arm within 42 days after start of treatment	42 days
Meth Hb concentration	day 7 methaemoglobin concentration	day 7

Collaborators and Investigators

• Sponsor: Menzies School of Health Research
• Collaborators: University of Melbourne; Curtin University; Addis Ababa University; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; Papua New Guinea Institute of Medical Research; Arba Minch University; Papuan Community Health and Development Foundation, Indonesia; Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Indonesia
• Investigators: Principal Investigator: Kamala N Thriemer, PhD, Menzies School of Health Research

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 19, 2023
• First Submitted That Met QC Criteria: November 19, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Vivax; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Primaquine; Tafenoquine
• Other Study ID Numbers: TADORE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No