A Phase 3 interventional study of Artemether-Lumefantrine-Amodiaquine (ALAQ) and Artemether-Lumefantrine (AL) in Uncomplicated Plasmodium Falciparum Malaria, sponsored by University of Oxford. Recruiting at 1 site in Rwanda. Open to participants aged 6 Months and older. Per ClinicalTrials.gov, last updated 2025-11-18.
Sponsored by University of Oxford · Phase 3, Interventional, and Treatment
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.
Study participants with an uncomplicated P. falciparum monoinfection complying with all the inclusion criteria and without any of the exclusion criteria will be enrolled and randomised to three arms TACT (ALAQ), ACT1 (AL), ACT2 (ASAQ) at the sites in Africa and two arms TACT (ALAQ) and ACT (AL) at the site in Asia. Competitive recruitment with overall trial sample size 1,680 subjects (840 ALAQ, 420 AL, 420 ASAQ, i.e. a 2:1:1 ratio overall). In lower transmission settings (Annual Parasite Incidence \<50 per 1000 population per year) the treatment will include a single 0.25 mg/kg gametocytocidal dose of primaquine as recommended by the World Health Organization (WHO) for patients ≥10 kg. Primaquine may be given if local treatment policy includes it.
Participants will be admitted for three days to an in-patient unit for directly observed treatment and to perform all the required study procedures from D0H0 (time of first dose intake) to D3 (H72). They will be followed up weekly starting D7 up to D42.
Microscopy to detect and quantify malaria parasitaemia will be performed daily (more frequently in participants with parasite density of >5000/µL at screening) during hospitalization and at all weekly and unscheduled visits. In participants with parasite densities >5000/µL at screening, parasite clearance rates will be assessed by repeated assessments of the parasite counts after the start of the antimalarial treatments. A capillary blood sample will be taken at each of the time-points for these parasite counts.
A physical examination and measurements of vital signs along with a symptom questionnaire will be performed and recorded through a standardized method at baseline, daily during admission and weekly during follow up through D42 and at all unscheduled visits.
Safety assessments will be performed by measuring markers of renal and hepatic toxicity, haemoglobin, platelet counts, absolute and differential white blood cell counts and electrocardiographs (ECGs). ECGs will be performed during hospitalization (H0, H4, and 4 hours after the last dose) and day 42 of follow up to assess and compare the effect of the TACT and ACTs on QT or corrected QT (QTc) intervals.
Pharmacokinetic measurements will be linked to measures of efficacy and toxicity. To reduce the burden of blood draws, especially in children, a population pharmacokinetic approach requiring sparse blood sampling will be followed in a subset of participants.
Blood samples for parasite genotyping as well as genomic and transcriptomic studies will be collected at baseline and also on the day of a recurrent infection. In selected study sites, P. falciparum parasites will be cryopreserved for in vitro antimalarial drug sensitivity testing. Where possible, ex vivo or in vitro assessments of parasite susceptibility to artemisinins and partner drugs will be assessed. The in vivo and ex vivo data on artemisinin and partner drug sensitivity will potentially be used to identify new genetic or transcriptomic markers/patterns of artemisinin or partner drug resistance.
The trial has been funded by Global Health Innovative Technology Fund.
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's planned enrollment of 1,680 is above the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TACT group
Drug: Artemether-Lumefantrine-Amodiaquine (ALAQ)
ACT 1 group
Drug: Artemether-Lumefantrine (AL)
ACT 2 group
Drug: Artesunate-Amodiaquine (ASAQ)
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).
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.
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.
28-day efficacy
28-day efficacy defined as the proportion of patients with Polymerase Chain Reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) at Day 28, i.e., absence up to Day 28 of P. falciparum parasitaemia (detected by microscopy) with parasites genetically identical to those detected at baseline (as determined by PCR product length polymorphisms)
Time frame: 28 days
28-day PCR uncorrected efficacy
28-day PCR uncorrected efficacy defined as the proportion of patients with absence up to Day 28 of P. falciparum parasitaemia
Time frame: 28 days
42-day efficacy
42-day efficacy defined as the proportion of patients with PCR-corrected adequate clinical and parasitological response (ACPR) at Day 42, i.e., absence up to Day 42 of P. falciparum parasitaemia (detected by microscopy) with parasites genetically identical to those detected at baseline (as determined by PCR product length polymorphisms)
Time frame: 42 days
42-day PCR-uncorrected efficacy
42-day PCR-uncorrected efficacy defined as the proportion of patients with absence up to Day 42 of P. falciparum parasitaemia
Time frame: 42 days
Parasite clearance half-life
Assessed by microscopy as primary parameter to determine parasite clearance half-life
Time frame: 3 days
Proportion of participants with microscopically detectable P. falciparum parasitaemia at Day 3
Time frame: 3 days
Fever clearance time
Fever clearance time (i.e., the time taken for the tympanic temperature to fall below 37.5°C in participants who were febrile at inclusion)
Time frame: 42 days
Proportion of participants with gametocytaemia
Proportion of participants with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment
Time frame: 42 days
Incidence of adverse events (AEs)
Incidence of AEs within the first 42 days including markers of hepatic, renal or bone marrow toxicity
Time frame: 42 days
Incidence of serious adverse events (SAEs)
Incidence of SAEs within the first 42 days including markers of hepatic, renal or bone marrow toxicity
Time frame: 42 days
Number of cardiotoxicity events
Cardiotoxicity in particular QT or QTc-interval above 500 ms at timepoint H4, H52 or H64, D42
Time frame: 42 days
Proportion of participants requiring retreatment due to vomiting
Proportion of participants requiring retreatment due to vomiting within 1 hour after administration of the study drugs
Time frame: 1 hour after administration of each dose of the treatment
Proportion of participants who report completing a full course of observed TACT
Proportion of participants who report completing a full course of observed TACT without withdrawal of consent or exclusion from study because of drug related serious adverse event
Time frame: 3 days
Proportion of participants who report completing a full course of observed ACT
Proportion of participants who report completing a full course of observed ACT without withdrawal of consent or exclusion from study because of drug related serious adverse event
Time frame: 2 or 3 days depending on the treatment
Peak plasma concentration
Peak plasma concentration (Cmax) of artemisinin-derivatives and partner drugs in ACT and TACT treated participants in correlation with pharmacodynamics measures of drug efficacy
Time frame: 42 days
Area under curve
Area under the plasma concentration versus time curve (AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated participants in correlation with pharmacodynamic measures of drug efficacy
Time frame: 42 days
Pharmacokinetic interactions - peak plasma concentration
Comparison of peak plasma concentration (Cmax) of artemisinin-derivatives and partner drugs in ACT and TACT treated participants in correlation with pharmacodynamics measures of drug efficacy
Time frame: 42 days
Pharmacokinetic interactions - area under curve
Comparison of area under the plasma concentration versus time curve (AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated participants in correlation with pharmacodynamic measures of drug efficacy
Time frame: 42 days
Plasma levels of partner drugs
Plasma levels of partner drugs in correlation with treatment efficacy and treatment arm on Day 7
Time frame: 7 days
Comparison of 28-day PCR-corrected efficacy of ALAQ vs AL
Comparison of 28-day PCR-corrected ACPR (as defined in outcome measure 1) of ALAQ vs AL in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 28 days
Comparison of 28-day PCR-uncorrected efficacy of ALAQ vs AL
Comparison of 28-day PCR-uncorrected efficacy (as defined in outcome measure 2) of ALAQ vs AL in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 28 days
Comparison of 42-day PCR-corrected efficacy of ALAQ vs AL
Comparison of 42-day PCR-corrected ACPR (as defined in outcome measure 3) of ALAQ vs AL in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 42 days
Comparison of 42-day PCR-uncorrected efficacy of ALAQ vs AL
Comparison of 42-day PCR-uncorrected efficacy (as defined in outcome measure 4) of ALAQ vs AL in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 42 days
Comparison of 28-day PCR-corrected efficacy of ALAQ vs ASAQ
Comparison of 28-day PCR-corrected ACPR (as defined in outcome measure 1) of ALAQ vs ASAQ in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 28 days
Comparison of 28-day PCR-uncorrected efficacy of ALAQ vs ASAQ
Comparison of 28-day PCR-uncorrected efficacy (as defined in outcome measure 2) of ALAQ vs ASAQ in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 28 days
Comparison of 42-day PCR-corrected efficacy of ALAQ vs ASAQ
Comparison of 42-day PCR-corrected ACPR (as defined in outcome measure 3) of ALAQ vs ASAQ in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 42 days
Comparison of 42-day PCR-uncorrected efficacy of ALAQ vs ASAQ
Comparison of 42-day PCR-uncorrected efficacy (as defined in outcome measure 4) of ALAQ vs ASAQ in infections with parasites carrying known and/or candidate markers of antimalarial drug resistance (mutations in pfkelch13, pfcrt, pfmdr1 and/or other markers, including those identified over the course of the study)
Time frame: 42 days
Proportions of recurrent infections with mutations
Proportions of recurrent infections with parasites carrying mutations known to be associated with recrudescence
Time frame: 42 days
Proportions of specimens collected at baseline with parasites carrying mutations
Proportions of specimens collected at baseline with parasites carrying mutations of known functional or operational significance (pfkelch13, pfcrt, pfmdr1, pfdhfr, pfdhps, pfplasmepsin2, and/or other parasite genetic markers associated with resistance or identified over the course of the study)
Time frame: Baseline
Change in haemoglobin concentration stratified for Glucose-6-Phosphate Dehydrogenase (G6PD) status/genotype
Change in haemoglobin concentration at day 3, 7, 28, stratified for G6PD status/genotype in participants receiving single low dose primaquine (SLD-PQ) vs those not receiving it
Time frame: 28 days
Comparison of transcriptomic patterns of drug sensitive and resistant parasites
Comparison of levels of RNA transcription before treatment and 6, 12 and 24 hours after start of treatment between parasites with or without known or putative markers of drug resistance
Time frame: 24 hours
Levels of RNA transcription coding for male or female specific gametocytes
Levels of RNA transcription coding for male or female specific gametocytes at admission up to day 14, stratified by the presence of gametocytes at enrolment
Time frame: 14 days
In vitro susceptibility of P. falciparum to artemisinins and partner drugs
In vitro susceptibility, measured as % survival after drug exposure or as half-maximal inhibitory concentration (IC50), of P. falciparum to artemisinins and partner drugs according to study sites and genotype
Time frame: 42 days
Ex vivo susceptibility of P. falciparum to artemisinins and partner drugs
Ex vivo susceptibility, measured as % survival after drug exposure or as IC50, of P. falciparum to artemisinins and partner drugs according to study sites and genotype
Time frame: 42 days
Plan to share: Yes — With participant's consent, participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the Mahidol Oxford Tropical Medicine Research Unit (MORU) data sharing policy with other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records or through interviews.
Time frame: After completion of the trial activities and reporting
Access criteria: MORU data sharing policy
Data sharing details ↗ · www.tropmedres.ac
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