A Study to Find Out if a Combination of 3 Medicines for the Treatment of Malaria Works as Well and is as Safe and Tolerable as Combinations of 2 Medicines

Summary

The goal of this open-label randomised, controlled, non-inferiority trial is to assess and compare the efficacy, tolerability and safety of a fixed dose TACT artemether-lumefantrine-amodiaquine (ALAQ) to the ACTs artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ) (with single low-dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria in patient. The main question it aims to answer is whether ALAQ, a fixed dose TACT, is as efficacious, safe and tolerable in comparison with AL and ASAQ.

Participants will be enrolled, admitted and randomised to receive the study drug (ALAQ, AL or ASAQ). Patients will receive directly observed treatments and will be followed up at least once daily for the first 3 days after enrolment followed by weekly visits from D7 up to D42. Patients will be asked to report to the clinics between scheduled visits in case of any illness or other symptoms or complaints.

Conditions

• Uncomplicated Plasmodium Falciparum Malaria

Interventions

DRUG

Artemether-Lumefantrine-Amodiaquine (ALAQ)

A new fixed-dose combination containing artemether, lumefantrine and amodiaquine (ALAQ) will be used in the trial. Each paediatric (dispersible) tablet will contain 20 mg artemether, 120 mg lumefantrine, 40 mg amodiaquine. Two formulations of (non-dispersible/hard) tablets, containing 50 mg or 60 mg artemether, 300 or 360 mg lumefantrine and 100 or 120 mg amodiaquine, will be used for adolescents or adults. The treatments will be administered in 6 doses over 3 days at H0, H8, H24, H36, H48 and H60. The target dosing will be in line with the ranges recommended by the WHO (total dose of 5-24 mg/kg of artemether, 29-144 mg/ kg of lumefantrine, 22.5-45 mg/kg of amodiaquine).

DRUG

Artemether-Lumefantrine (AL)

A fixed-dose combination of AL will be used in the trial. Each paediatric (dispersible or non-dispersible) tablet will contain 20 mg artemether, 120 mg lumefantrine and adult (non-dispersible) tablets will contain 80 mg artemether, 480 mg lumefantrine. Treatment doses will be administered in 6 doses over 3 days at H0, H8, H24, H36, H48 and H60. The target dosing will be in line with the ranges recommended by the WHO.

DRUG

Artesunate-Amodiaquine (ASAQ)

ASAQ will also be administered as a fixed dose combination. The tablets will contain 25 mg of artesunate and 67.5 mg of amodiaquine in the paediatric formulation and 100 mg artesunate, 270 mg amodiaquine in the adult formulation. The dosing will be administered once a day for 3 days at H0, H24 and H48 according to the schedule currently recommended by the WHO.

Sponsors & Collaborators

• University of Oxford

  lead OTHER

Principal Investigators

• Mehul Dhorda, Ph.D · Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

• Arjen Dondorp, Prof. · Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-11

Primary Completion

2026-07-31

Completion

2026-07-31

Countries

• Rwanda

Study Locations