Acute Uncomplicated Plasmodium Falciparum MalariaPhase 2NCT03167242
Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
A Phase 2 study testing KAF156, Coartem and Lumefantrine Solid Dispersion Formulation in people with Acute Uncomplicated Plasmodium Falciparum Malaria, run by Novartis Pharmaceuticals at 11 sites in 9 countries.
Trial summary
This study was designed to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated Plasmodium falciparum malaria. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Acute Uncomplicated Plasmodium Falciparum Malaria
- What is being tested?
- KAF156, Coartem and Lumefantrine Solid Dispersion Formulation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 524 participants
- Where
- 11 sitesin 9 countries
- Study dates
- 2 Aug 2017to 28 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg. Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included.
- Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films.
- P. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/µL at the time of pre-screening (i.e., Study Visit 1).
- Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.3 ºC; or similar history of fever during the previous 24 hours (history of fever must be documented).
- Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients < 18 years old, who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines.
Who cannot join
- Mixed Plasmodium infections.
- Signs and symptoms of severe malaria according to WHO (World Health Organization) 2015 criteria unless characterized by high parasitaemia only.
- Patients with concurrent febrile illnesses (e.g., typhoid fever).
- Severe vomiting, defined as more than 3 times in the 24 hours prior to inclusion in the study or severe diarrhea defined as more than 3 watery stools per day.
- Pregnant or nursing (lactating) women.
- Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia.
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- Anemia (Hemoglobin level < 8 g/dL).
- Patients with prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five (5) plasma half-lives (or within 4 weeks of screening if half-life is unknown).
- History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc (heart rate-corrected QT) interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient's medical history and/or clinical or laboratory evidence of any of the following:
- AST/ALT > 2 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
- AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN
- Total bilirubin > 2 x ULN, regardless of the level of AST/ALT
Trial locations and contacts
11 sites in 9 countries.
11 sites in 9 countries
Kenya2 sites
Novartis Investigative Site
Kombewa
Novartis Investigative Site
Siaya, 2300
Uganda2 sites
Novartis Investigative Site
Masaka
Novartis Investigative Site
Tororo
About this study
Official title: A Phase 2 Interventional, Multicenter, Randomized Open Label Study to Determine the Effective and Tolerable Dose of KAF156 and Lumefantrine Solid Dispersion Formulation in Combination, Given Once Daily for 1, 2 and 3-days to Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
This study was designed to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated Plasmodium falciparum malaria.
There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.
Read the detailed description
This was a Phase 2 multi-center and open-label study with a single cohort pharmacokinetic (PK) Run-in Part followed by 2 randomized parallel-group parts, Part A and Part B, in adults and children with confirmed and uncomplicated Plasmodium falciparum malaria. Each part (PK Run-in, Part A and Part B) had the same design structure: A screening phase of up to 24 hours where participants were evaluated for eligibility and randomized (Part A and B) into different cohorts. A treatment phase of up to 3 days where participants were treated for 1, 2 or 3 consecutive days. Finally, participants were followed up until Day 43, where the rescue medication was the local standard at the discretion of the Investigator and participants
PK Run-in part: Adult/adolescent participants (≥ 12 years old) were dosed with a single dose of 200 mg KAF156 and 960 mg LUM-SDF at Day 1. The purpose of this part was to assess potential PK interactions between the compounds when dosed together.
Part A: Adult/adolescent participants (≥ 12 years old) were randomized into one of seven cohorts in a 2:2:2:2:2:2:1 ratio: six KAF156 and LUM-SDF cohorts at starting doses of 400 mg and 480 mg once daily (QD) for 1 day respectively and a control arm (Coartem twice a day (BID) for 3 days). Upon completion of Part A, all the dosing groups were evaluated in an interim assessment to determine the effective and tolerated KAF156 and LUM-SDF dosing regimen and dosages to be used in Part B.
Part B: Children participants (2 to < 12 years old) were randomized to three KAF156 and LUM-SDF cohorts at dosages and dosing regimens selected from Part A and the control arm (Coartem) in a 2:2:2:1 ratio.
- Being tested
- KAF156, Coartem, Lumefantrine Solid Dispersion Formulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KAF156Drug
Also called KAF
KAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses.
CoartemDrug
Coartem comes as 20/120 mg dispersible tablets or 80/480 mg tablets for oral administration. Coartem was administered twice daily for 3 days as active comparator.
Lumefantrine Solid Dispersion FormulationDrug
Also called LUM-SDF and LUM
LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses.
| Study group | Role | What they receive |
|---|---|---|
| Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day | Experimental | Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 day | Experimental | Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 days | Experimental | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 days | Experimental | Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 days | Experimental | Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 days | Experimental | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part A - Cohort 7: Coartem | Active comparator | Participants received Coartem twice daily via oral administration for 3 days Receives: Drug: Coartem |
| PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 day | Experimental | Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day | Experimental | Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 days | Experimental | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 days | Experimental | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days Receives: Drug: KAF156; Drug: Lumefantrine Solid Dispersion Formulation |
| Part B - Cohort 4: Coartem | Active comparator | Participants received Coartem twice daily via oral administration for 3 days Receives: Drug: Coartem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at Day 29 (i.e., 28 days post first dose) based on the short half-life of the study drugs. Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection.
A participant was considered as PCR-corrected ACPR at Day 29 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia 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: 28 days post first dose
PK Run-in: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Treatment Dose (AUC0-24h) of KAF156
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. AUC0-24h was determined using non-compartmental methods.
Measured: 0, 1, 3, 6, 12, 18 and 24 hours post-dose
Secondary outcomes (11)
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR)
PCR-uncorrected ACPR defined as the absence of parasitaemia was evaluated at days 15, 29 and 43 (i.e., 14, 28 and 42 days post first dose).
A participant was considered as PCR-uncorrected ACPR at Days 15, 29 or 43 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Days 15, 29 or 43 irrespective of axillary temperature.
Measured: 14, 28 and 42 days post first dose
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR)
PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at days 15 and 43 (i.e., 14 and 42 days post first dose). Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection.
A participant was considered as PCR-corrected ACPR at Day 15 or Day 43 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 15 or Day 43 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia 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: 14 and 42 days post first dose
Part A and Part B: 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 must be confirmed by PCR analysis.
Measured: 42 days post first dose
Part A and Part B: Number of Participants With Reinfection Events
Reinfection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. Reinfection must be confirmed by PCR analysis.
Measured: 42 days post first dose
Part A and Part B: Fever Clearance Time (FCT)
Fever Clearance Time (FCT) is defined as the 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. In case a participant received rescue medication before (fever) clearance, the time to event was censored at the first use of rescue medication.
Measured: 42 days post first dose
PK Run-in, Part A and Part B: Parasite Clearance Time (PCT)
Parasite Clearance Time (PCT) is defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. In case a participant received rescue medication before (parasite) clearance, the time to event was censored at the first use of rescue medication.
Measured: 42 days post first dose
PK Run-in, Part A and Part B: Number of Participants With Parasitaemia
Parasitaemia is the quantitative content of parasites in the blood determined by microscopy examination validated methods. Only Plasmodium Falciparum asexual form is used for parasitaemia assessments.
Measured: 12, 24 and 48 hours post last dose
Part A and Part B: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Last Treatment Dose (AUC0-24h) of KAF156
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. AUC0-24h was determined using non-compartmental methods.
Measured: 3, 6, 18 and 24 hours post last dose
Part A and Part B: Maximum Peak Observed Concentration (Cmax) of KAF156
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. Cmax was determined using non-compartmental methods.
Measured: 3, 6, 18, 24, 27, 30, 48, 51, 54, 68, 72 and 168 hours post last dose
PK Run-in and Part A: Elimination Half-life (T½) of KAF156
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. T½ was determined using non-compartmental methods.
Measured: 0, 1, 3, 6, 12, 18, 24, 27, 30, 36, 48, 72, 96 and 168 hours post last dose
PK Run-in and Part A (Cohorts 1 and 2): Time to Reach Maximum Blood Concentrations (Tmax) of KAF156
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. Tmax was determined using non-compartmental methods.
Measured: 0, 1, 3, 6, 12, 18, 24, 30, 48, 96 and 168 hours post last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start2 Aug 2017
- Primary completion14 Jun 2021
- Study completion28 Jun 2021
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 (3)Papers the sponsor has linked to this study.
- Other trials for Acute Uncomplicated 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 524 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03167242
- Sponsor's protocol ID
- CKAF156A2202
- Other IDs
- 2020-003284-25
- Status last verified
- Dec 2021
- First submitted
- 19 May 2017
- Last updated
- 10 Feb 2022
- 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 https://www.clinicalstudydatarequest.com/.
Publications
Shin E, Bhat AG, Ramanathan M. Large Language Models for Clinical Trial Protocol Assessments. Clin Pharmacol Ther. 2026 Feb;119(2):393-402. doi: 10.1002/cpt.70096. Epub 2025 Oct 21.
PubMed 41121745Sangana R, Ogutu B, Yeka A, Kusemererwa S, Tinto H, Toure AO, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, Landry N'Guessan T, Nassa GJW, Nyantaro M, Tina LO, Anvikar A, Sinha A, Kaguthi G, Fofana B, Grobusch MP, Gaaloul ME, Marrast AC, Pathan R, Chikoto H, Csermak K, Risterucci C, Su G, Winnips C, Zhang J, Zack J. Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study. J Clin Pharmacol. 2025 Feb;65(2):179-189. doi: 10.1002/jcph.6138. Epub 2024 Sep 29.
PubMed 39344281Ogutu B, Yeka A, Kusemererwa S, Thompson R, Tinto H, Toure AO, Uthaisin C, Verma A, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, N'Guessan TL, Nassa GJW, Nyantaro M, Tina LO, Singh PK, El Gaaloul M, Marrast AC, Chikoto H, Csermak K, Demin I, Mehta D, Pathan R, Risterucci C, Su G, Winnips C, Kaguthi G, Fofana B, Grobusch MP. Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial. Lancet Infect Dis. 2023 Sep;23(9):1051-1061. doi: 10.1016/S1473-3099(23)00209-8. Epub 2023 Jun 13.
PubMed 37327809
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Interventional, Multicenter, Randomized Open Label Study to Determine the Effective and Tolerable Dose of KAF156 and Lumefantrine Solid Dispersion Formulation in Combination, Given Once Daily for 1, 2 and 3-days to Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
- ClinicalTrials.gov ID
- NCT03167242
- Acronym / sponsor ID
- CKAF156A2202
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 524 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Study start
- 2 Aug 2017 (actual)
- Primary completion
- 14 Jun 2021 (actual)
- Study completion
- 28 Jun 2021 (actual)
- First posted
- 25 May 2017 (actual)
- Results
- Posted 10 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was designed to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated Plasmodium falciparum malaria.
There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.
Detailed description
This was a Phase 2 multi-center and open-label study with a single cohort pharmacokinetic (PK) Run-in Part followed by 2 randomized parallel-group parts, Part A and Part B, in adults and children with confirmed and uncomplicated Plasmodium falciparum malaria. Each part (PK Run-in, Part A and Part B) had the same design structure: A screening phase of up to 24 hours where participants were evaluated for eligibility and randomized (Part A and B) into different cohorts. A treatment phase of up to 3 days where participants were treated for 1, 2 or 3 consecutive days. Finally, participants were followed up until Day 43, where the rescue medication was the local standard at the discretion of the Investigator and participants
PK Run-in part: Adult/adolescent participants (≥ 12 years old) were dosed with a single dose of 200 mg KAF156 and 960 mg LUM-SDF at Day 1. The purpose of this part was to assess potential PK interactions between the compounds when dosed together.
Part A: Adult/adolescent participants (≥ 12 years old) were randomized into one of seven cohorts in a 2:2:2:2:2:2:1 ratio: six KAF156 and LUM-SDF cohorts at starting doses of 400 mg and 480 mg once daily (QD) for 1 day respectively and a control arm (Coartem twice a day (BID) for 3 days). Upon completion of Part A, all the dosing groups were evaluated in an interim assessment to determine the effective and tolerated KAF156 and LUM-SDF dosing regimen and dosages to be used in Part B.
Part B: Children participants (2 to < 12 years old) were randomized to three KAF156 and LUM-SDF cohorts at dosages and dosing regimens selected from Part A and the control arm (Coartem) in a 2:2:2:1 ratio.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg |
| Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 day | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg |
| Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 days | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days |
| Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 days | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days |
| Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 days | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days |
| Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 days | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days |
| Part A - Cohort 7: Coartem | Active comparator | Drug: CoartemParticipants received Coartem twice daily via oral administration for 3 days |
| PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 day | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg |
| Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg |
| Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 days | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days |
| Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 days | Experimental | Drug: KAF156, Drug: Lumefantrine Solid Dispersion FormulationParticipants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days |
| Part B - Cohort 4: Coartem | Active comparator | Drug: CoartemParticipants received Coartem twice daily via oral administration for 3 days |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg. Part B: after determining the effective/tolerated doses and regimens in adolescent and adult patients, male and female patients ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included.
- Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films.
- P. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/µL at the time of pre-screening (i.e., Study Visit 1).
- Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.3 ºC; or similar history of fever during the previous 24 hours (history of fever must be documented).
- Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients < 18 years old, who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines.
Key exclusion criteria (13 listed)
- Mixed Plasmodium infections.
- Signs and symptoms of severe malaria according to WHO (World Health Organization) 2015 criteria unless characterized by high parasitaemia only.
- Patients with concurrent febrile illnesses (e.g., typhoid fever).
- Severe vomiting, defined as more than 3 times in the 24 hours prior to inclusion in the study or severe diarrhea defined as more than 3 watery stools per day.
- Pregnant or nursing (lactating) women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KAF156Also: KAFKAF156 comes in 100 mg tablets for oral administration. KAF156 was administered in combination with LUM-SDF once daily (QD) for 1, 2 or 3 days at 200 mg, 400 mg or 800 mg doses. | Drug | PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 day, Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day, Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 day, Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 days, Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 days, Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 days, Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 days, Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day, Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 days, Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 days |
| CoartemCoartem comes as 20/120 mg dispersible tablets or 80/480 mg tablets for oral administration. Coartem was administered twice daily for 3 days as active comparator. | Drug | Part A - Cohort 7: Coartem, Part B - Cohort 4: Coartem |
| Lumefantrine Solid Dispersion FormulationAlso: LUM-SDF and LUMLUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses. | Drug | PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 day, Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day, Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 day, Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 days, Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 days, Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 days, Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 days, Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day, Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 days, Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 days |
Primary outcome
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29
Time frame: 28 days post first dose
PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at Day 29 (i.e., 28 days post first dose) based on the short half-life of the study drugs. Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR at Day 29 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia 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.
PK Run-in: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Treatment Dose (AUC0-24h) of KAF156
Time frame: 0, 1, 3, 6, 12, 18 and 24 hours post-dose
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. AUC0-24h was determined using non-compartmental methods.
11 secondary outcomes
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Uncorrected Adequate Clinical and Parasitological Response (ACPR)
Time frame: 14, 28 and 42 days post first dose
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR)
Time frame: 14 and 42 days post first dose
Part A and Part B: Number of Participants With Recrudescence Events
Time frame: 42 days post first dose
Part A and Part B: Number of Participants With Reinfection Events
Time frame: 42 days post first dose
Part A and Part B: Fever Clearance Time (FCT)
Time frame: 42 days post first dose
PK Run-in, Part A and Part B: Parasite Clearance Time (PCT)
Time frame: 42 days post first dose
PK Run-in, Part A and Part B: Number of Participants With Parasitaemia
Time frame: 12, 24 and 48 hours post last dose
Part A and Part B: Area Under the Blood Concentration-time Curve Over the Last 24 Hours After Last Treatment Dose (AUC0-24h) of KAF156
Time frame: 3, 6, 18 and 24 hours post last dose
Part A and Part B: Maximum Peak Observed Concentration (Cmax) of KAF156
Time frame: 3, 6, 18, 24, 27, 30, 48, 51, 54, 68, 72 and 168 hours post last dose
PK Run-in and Part A: Elimination Half-life (T½) of KAF156
Time frame: 0, 1, 3, 6, 12, 18, 24, 27, 30, 36, 48, 72, 96 and 168 hours post last dose
PK Run-in and Part A (Cohorts 1 and 2): Time to Reach Maximum Blood Concentrations (Tmax) of KAF156
Time frame: 0, 1, 3, 6, 12, 18, 24, 30, 48, 96 and 168 hours post last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41121745Shin E, Bhat AG, Ramanathan M. Large Language Models for Clinical Trial Protocol Assessments. Clin Pharmacol Ther. 2026 Feb;119(2):393-402. doi: 10.1002/cpt.70096. Epub 2025 Oct 21.
- Derived from this study: PubMed 39344281Sangana R, Ogutu B, Yeka A, Kusemererwa S, Tinto H, Toure AO, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, Landry N'Guessan T, Nassa GJW, Nyantaro M, Tina LO, Anvikar A, Sinha A, Kaguthi G, Fofana B, Grobusch MP, Gaaloul ME, Marrast AC, Pathan R, Chikoto H, Csermak K, Risterucci C, Su G, Winnips C, Zhang J, Zack J. Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study. J Clin Pharmacol. 2025 Feb;65(2):179-189. doi: 10.1002/jcph.6138. Epub 2024 Sep 29.
- Derived from this study: PubMed 37327809Ogutu B, Yeka A, Kusemererwa S, Thompson R, Tinto H, Toure AO, Uthaisin C, Verma A, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, N'Guessan TL, Nassa GJW, Nyantaro M, Tina LO, Singh PK, El Gaaloul M, Marrast AC, Chikoto H, Csermak K, Demin I, Mehta D, Pathan R, Risterucci C, Su G, Winnips C, Kaguthi G, Fofana B, Grobusch MP. Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial. Lancet Infect Dis. 2023 Sep;23(9):1051-1061. doi: 10.1016/S1473-3099(23)00209-8. Epub 2023 Jun 13.
- Individual participant dataSharing planned: 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 https://www.clinicalstudydatarequest.com/.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Novartis Pharmaceuticals
11 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KAF156, Coartem and Lumefantrine Solid Dispersion Formulation in people with Acute Uncomplicated Plasmodium Falciparum Malaria, run by Novartis Pharmaceuticals at 11 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Kenya, Uganda, Burkina Faso, Gabon, India and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A and Part B: Number of Participants With Polymerase Chain Reaction (PCR)-Corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 (time frame: 28 days post first dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03167242, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2022.