Plasmodium Falciparum MalariaPhase 2/3CALINANCT04300309
Pharmacokinetics, Safety, Tolerability and Efficacy of a New Artemether-lumefantrine Dispersible Tablet in Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria
A Phase 2/3 study testing artemether:lumefantrine (2.5 mg:30 mg) in people with Plasmodium Falciparum Malaria, run by Novartis Pharmaceuticals at 3 sites in 2 countries.
Trial summary
The purpose of this study was to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria. Read more about this study
- Who is it for?
- Ages Up to 365 days
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- artemether:lumefantrine (2.5 mg:30 mg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 21 Dec 2020to 10 May 2024
- Phase
- Phase 2/3
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 Up to 365 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female neonates/infants
- Body weight <5 kg but ≥ 2 kg
- In Cohort 1, infants aged >28 days; in Cohort 2, neonates aged 1 to ≤28 days (3 subgroups: 1-7 days; 8-14 days; 15-28 days)
- Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections):
- in Cohort 1 of ≥500 and <100,000 parasites/µL asexual P. falciparum parasitemia
- in Cohort 2 of ≥100 and <100,000 parasites/µL asexual P. falciparum parasitemia
- either congenital or neonatal
- either symptomatic or asymptomatic
Who cannot join
- Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly)
- Presence of severe malaria (according to WHO 2015 definition)
- HIV status :
- in Cohort 1, patient's or patient's mother's current treatment with ARV
- in Cohort 2, mother's known HIV positive status at patient's birth or mother's current treatment with ARV
- Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants) (WHO 2005)
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- Presence of any clinically significant neurological condition:
- any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs)
- known neurological disorders (e.g. chronic seizure disorders, cerebral palsy)
- Presence of clinically significant abnormality of the hepatic and renal systems
- Patients unable to swallow or whose drinking is impaired
- Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes
- History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion
- Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
- Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia)
- Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities
- Patients who received any antimalarial drug, including antibiotics with antimalarial activity, within 14 days of trial start, or any other prohibited drug (see Table 6-2)
- Patients who received an investigational drug within 5 half-lives of enrollment or participated in an investigational study or within 30 days, whichever is longer
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Burkina Faso2 sites
Novartis Investigative Site
Nanoro
Novartis Investigative Site
Ouagadougou
Democratic Republic of the Congo1 site
Novartis Investigative Site
Kisantu, Bas Kongo
About this study
Official title: Multicenter, Open-label, Single-arm Study to Evaluate the PK, Safety, Tolerability and Efficacy of a New Artemether:Lumefantrine (2.5 mg:30 mg) Dispersible Tablet in the Treatment of Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria
The purpose of this study was to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.
Read the detailed description
This was a multicenter, open-label, single-arm, adaptive design with dose adaptation (deescalation or escalation) study in infants and neonates <5 kg body weight with P. falciparum malaria. There were two sequential and age-descending cohorts of participants, all <5 kg: Cohort 1 of infants >28 days of age, and Cohort 2 of neonates ≤ 28 days of age.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- artemether:lumefantrine (2.5 mg:30 mg)
- Keywords
- Plasmodium falciparum, malaria, artemether, lumefantrine, neonates, infants
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
artemether:lumefantrine (2.5 mg:30 mg)Drug
Two oral dispersible tablets twice daily for three consecutive days. Each tablet contained artemether-lumefantrine 2.5 mg:30 mg.
| Study group | Role | What they receive |
|---|---|---|
| artemether lumefantrine (2.5 mg:30 mg) | Experimental | Artemether-lumefantrine (5 mg:60 mg) twice daily for 3 days Receives: Drug: artemether:lumefantrine (2.5 mg:30 mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Artemether Cmax After First Dose
Artemether Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose.
Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on artemether plasma concentrations.
Measured: 1 and 2 hours after first dose (Day 1)
Secondary outcomes (12)
Lumefantrine Day 8 Concentration (C168h)
Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations.
Dosing times were 0, 8, 24, 36, 48 and 60 hours.
Measured: 168 hours after first dose (corresponding to 108 hours after last dose)
Lumefantrine Cmax After Last Dose
Lumefantrine Cmax represents the highest concentration among four sampling time points after last dose.
Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on lumefantrine plasma concentrations.
Dosing times were 0, 8, 24, 36, 48 and 60 hours.
Measured: 62, 66, 68 and 84 hours after first dose (corresponding to 2, 6, 8 and 24 hours after last dose)
DHA Cmax After First Dose
Dihydroartemisinin (DHA) is an active metabolite of artemether. DHA Cmax represents the highest concentration between the concentrations at 1 hour and 2 hours after first dose.
Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis based on DHA plasma concentrations.
Measured: 1 and 2 hours after first dose (Day 1)
Parasite Clearance Time (PCT)
PCT is defined as time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. PCT is based on uncorrected parasite counts.
Patients who received rescue medication before parasite clearance were censored at the first use of rescue medication.
Patients without parasite clearance were censored at the time of last parasite assessment.
PCT was calculated using the Kaplan-Meier method.
Measured: Up to 48 hours after first dose
Fever Clearance Times (FCT)
FCT is defined as time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours.
Patients who received rescue medication before fever clearance were censored at the first use of rescue medication.
Patients without fever clearance were censored at the time of last parasite assessment.
FCT was calculated using the Kaplan-Meier method.
Measured: Up to 36 hours after first dose
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - PPS Analysis
PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection.
A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.
Measured: Days 15, 29 and 43
PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - FAS Analysis
PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Days 15, 29 and 43. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection.
A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.
Measured: Days 15, 29 and 43
PCR-uncorrected Adequate Clinical and Parasitological Response (ACPR)
PCR-uncorrected ACPR, defined as the absence of parasitemia, was evaluated on Days 8, 15, 29 and 43.
A participant was considered as PCR-uncorrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 8, 15, 29 or 43 irrespective of axillary temperature.
Measured: Days 8, 15, 29 and 43
Number of Participants With Recrudescence Events
Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Recrudescence had to be confirmed by PCR analysis.
Measured: Days 15, 29 and 43
Number of Participants With New Infections Events
New infection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. New infection had to be confirmed by PCR analysis.
Measured: Days 15, 29 and 43
Number of Participants With Adverse Events (AEs)
Number of participants with adverse events (any AEs regardless of seriousness), including changes in laboratory results qualifying and reported as adverse events.
Measured: From first dose of study treatment until Day 43
Number of Participants With Serious Adverse Events (SAEs)
Number of participants with serious adverse events (SAEs), including changes in laboratory results qualifying and reported as serious adverse events.
Measured: From first dose of study treatment until 12 months of age (assessed up to maximum 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2020
- Study start21 Dec 2020
- Primary completion2 Jul 2023
- Study completion10 May 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP), Medicines for Malaria Venture, Groupe de Recherche Action en Sante, Institut de Recherche en Sciences de la Sante, Burkina Faso
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04300309
- Sponsor's protocol ID
- CCOA566B2307
- Other IDs
- PACTR202004535453508
- Acronym
- CALINA
- Status last verified
- Dec 2025
- First submitted
- 18 Feb 2020
- Last updated
- 13 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Wounounou G, Tiono AB, Ogutu B, Manyando C, Sagara I, Schneitter S, Bassat Q, Gaaloul ME, Marrast AC, Demin I, Winnips C, Risterucci C, Hugot S, Hofstetter G, Qian Z, Su G, Zhang J, Renner KC, Cousin M, Venishetty VK, Sayyed S, Gandhi P, Kabore B; CALINA study group. Pharmacokinetics, safety and efficacy of an optimized dose of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in neonates and infants of less than 5 kg body weight: a multicentre, open-label, single-arm phase 2/3 study (CALINA). Trop Med Health. 2025 Nov 6;53(1):151. doi: 10.1186/s41182-025-00828-z.
PubMed 41199347