Uncomplicated Plasmodium Falciparum MalariaPhase 3FD-TACTNCT05951595
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
A Phase 3 study testing Artemether-Lumefantrine-Amodiaquine (ALAQ), Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine (ASAQ) in people with Uncomplicated Plasmodium Falciparum Malaria, run by University of Oxford at 1 site in Rwanda.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Uncomplicated Plasmodium Falciparum Malaria
- What is being tested?
- Artemether-Lumefantrine-Amodiaquine (ALAQ), Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine (ASAQ)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,680 participants
- Where
- 1 siteRwanda
- Study dates
- 11 Sep 2025to 31 Jul 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, aged ≥6 months (no upper limit unless one is required by local regulations) and bodyweight ≥5 kg
- Ability to take oral medication
- Fever defined as ≥38°C tympanic temperature or a history of fever within the last 24 hours
- Acute uncomplicated P. falciparum monoinfection
- Asexual P. falciparum parasitaemia: 1,000/µL to 250,000/µL determined on a peripheral blood film
- Written informed consent by the participant, or by the parent/guardian in case of children lower than the age of consent, and assent if required (per local regulations)
- Willingness and ability of the participants or parents/guardians to comply with the study protocol for the duration of the study
Who cannot join
- Signs of severe malaria (adapted from WHO criteria)
- Patients not fulfilling criteria for severe malaria but with other indication(s) for parenteral antimalarial treatment at the discretion of the treating physician
- Haemoglobin <7 g/dL at screening
- Participants who have received artemisinin or a derivative within the previous 7 days OR lumefantrine or amodiaquine within the previous 14 days
- In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within the last 30 days
- Acute illness other than malaria requiring systemic treatment
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- Severe acute malnutrition
- Known HIV, tuberculosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other severe infection
- For women of child-bearing age: pregnant, trying to get pregnant or lactating
- History of allergy or known contraindication to any of the study drugs, including neuropsychiatric disorders and epilepsy
- Previous splenectomy
- Participation in the previous 3 months and/or ongoing follow-up for an interventional study (including FD-TACT)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Rwanda1 site, 1 recruiting
- Recruiting
Ruhuha Health Centre
Ruhuha, Eastern Province
Leon Mutesa, MD PhD, +250 788 451 013, lmutesa@gmail.com
Raphael Ndahimana, MSc, +250 789 926 345, ndahimana.raphael@gmail.com
About this study
Official title: An Open-label, Randomised, Controlled, Non-inferiority Trial to Compare the Efficacy, Safety and Tolerability of a Fixed Dose Triple Artemisinin-based Combination Therapy (TACT) Artemether-lumefantrine-amodiaquine Versus First-line Artemisinin-based Combination Therapies (ACTs) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria
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.
Read the detailed description
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.
- Being tested
- Artemether-Lumefantrine-Amodiaquine (ALAQ), Artemether-Lumefantrine (AL), Artesunate-Amodiaquine (ASAQ)
- Keywords
- Artemether, Lumefantrine, Amodiaquine, Artesunate, Triple Artemisinin-based Combination Therapy (TACT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-Lumefantrine-Amodiaquine (ALAQ)Drug
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).
Artemether-Lumefantrine (AL)Drug
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.
Artesunate-Amodiaquine (ASAQ)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Artemether-Lumefantrine-Amodiaquine (ALAQ) | Experimental | TACT group Receives: Drug: Artemether-Lumefantrine-Amodiaquine (ALAQ) |
| Artemether-Lumefantrine (AL) | Active comparator | ACT 1 group Receives: Drug: Artemether-Lumefantrine (AL) |
| Artesunate-Amodiaquine (ASAQ) | Active comparator | ACT 2 group Receives: Drug: Artesunate-Amodiaquine (ASAQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 28 days
Secondary outcomes (18)
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
Measured: 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)
Measured: 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
Measured: 42 days
Parasite clearance half-life
Assessed by microscopy as primary parameter to determine parasite clearance half-life
Measured: 3 days
Proportion of participants with microscopically detectable P. falciparum parasitaemia at Day 3
Measured: 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)
Measured: 42 days
Proportion of participants with gametocytaemia
Proportion of participants with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment
Measured: 42 days
Incidence of adverse events (AEs)
Incidence of AEs within the first 42 days including markers of hepatic, renal or bone marrow toxicity
Measured: 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
Measured: 42 days
Number of cardiotoxicity events
Cardiotoxicity in particular QT or QTc-interval above 500 ms at timepoint H4, H52 or H64, D42
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 42 days
Plasma levels of partner drugs
Plasma levels of partner drugs in correlation with treatment efficacy and treatment arm on Day 7
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2023
- Study start11 Sep 2025
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,680 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mehul Dhorda, Ph.D, Principal investigator, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandArjen Dondorp, Prof., Principal investigator, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05951595
- Sponsor's protocol ID
- MAL23001
- Acronym
- FD-TACT
- Status last verified
- Oct 2025
- First submitted
- 19 Jun 2023
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.