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    Clinical Trial Results:
    A randomized, open-label, multicenter study to compare efficacy, safety and tolerability of KLU156 with Coartem® in the treatment of uncomplicated Plasmodium falciparum malaria in adults and children ≥ 5 kg body weight followed by an Extension phase with repeated KLU156 treatment

    Summary
    EudraCT number
    		 2022-002675-10
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    25 Nov 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Jun 2026
    First version publication date
    09 Jun 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CKLU156A12301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05842954
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Nov 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Nov 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to confirm the efficacy of KLU156 in adults and children ≥ 10 kg body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) by demonstrating that KLU156 is non-inferior to Coartem (non‑inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Mar 2024
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Burkina Faso: 379
    Country: Number of subjects enrolled
    Congo, The Democratic Republic of the: 198
    Country: Number of subjects enrolled
    Côte d’Ivoire: 242
    Country: Number of subjects enrolled
    Gabon: 80
    Country: Number of subjects enrolled
    Ghana: 163
    Country: Number of subjects enrolled
    Kenya: 175
    Country: Number of subjects enrolled
    Mali: 110
    Country: Number of subjects enrolled
    Niger: 8
    Country: Number of subjects enrolled
    Rwanda: 163
    Country: Number of subjects enrolled
    Tanzania, United Republic of: 56
    Country: Number of subjects enrolled
    Uganda: 89
    Country: Number of subjects enrolled
    Zambia: 57
    Worldwide total number of subjects
    1720
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    53
    Children (2-11 years)
    1042
    Adolescents (12-17 years)
    314
    Adults (18-64 years)
    307
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Patients were screened at 35 centers in 13 countries across Sub-Saharan Africa and India.

    Period 1
    Period 1 title
    Core Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Assessor [1]

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 KLU156 (Participants with ≥10 kg Body Weight)
    Arm description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).
    Arm type
    		 Experimental

    Investigational medicinal product name
    KLU156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.

    Arm title
    		 Coartem (Participants with ≥10 kg Body Weight)
    Arm description
    		 Coartem twice a day (BID) for 3 days under fed conditions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Coartem
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. Dosing was selected based on patient’s body weight as per product's label.

    Arm title
    		 KLU156 (Participants with <10 kg Body Weight)
    Arm description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).
    Arm type
    		 Experimental

    Investigational medicinal product name
    KLU156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.

    Arm title
    		 Coartem (Participants with <10 kg Body Weight
    Arm description
    		 Coartem twice a day (BID) for 3 days under fed conditions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Coartem
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. Dosing was selected based on patient’s body weight as per product's label.

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: assessor blinded
    Number of subjects in period 1
    		KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight) KLU156 (Participants with <10 kg Body Weight) Coartem (Participants with <10 kg Body Weight
    Started
    836
    832
    24
    28
    Safety set
    830
    831
    24
    27
    Modified randomized set (mRAS)
    836
    832
    0 [2]
    0 [3]
    Modified safety set
    830
    831
    0 [4]
    0 [5]
    Completed
    767
    824
    14
    27
    Not completed
    69
    8
    10
    1
         Adverse event, non-fatal
    62
    5
    9
    -
         Protocol Deviation
    -
    1
    -
    -
         Technical Problems
    -
    -
    1
    -
         Guardian Decision
    1
    1
    -
    -
         Not Treated in Core
    6
    1
    -
    1
    Notes
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone provided to define analysis population
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone provided to define analysis population
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone provided to define analysis population
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone provided to define analysis population
    Period 2
    Period 2 title
    Extension Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Assessor [6]
    Blinding implementation details
    assessor blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 KLU156 (≥10 kg Body Weight Entering from Core KLU156 Arm)
    Arm description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).
    Arm type
    		 Experimental

    Investigational medicinal product name
    KLU156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.

    Arm title
    		 KLU156 (≥10 kg Body Weight Entering from Core Coartem Arm)
    Arm description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).
    Arm type
    		 Experimental

    Investigational medicinal product name
    KLU156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.

    Arm title
    		 KLU156 (<10 kg Body Weight Entering from Core KLU156 Arm)
    Arm description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).
    Arm type
    		 Experimental

    Investigational medicinal product name
    KLU156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral use. KLU156 (400/480 mg) was the dose for patients with a bodyweight ≥ 35kg. Patients < 35kg took a fraction of the dose according to weight group as defined in the protocol.

    Notes
    [6] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: assessor blinded
    Number of subjects in period 2 [7]
    		KLU156 (≥10 kg Body Weight Entering from Core KLU156 Arm) KLU156 (≥10 kg Body Weight Entering from Core Coartem Arm) KLU156 (<10 kg Body Weight Entering from Core KLU156 Arm)
    Started
    190
    203
    2
    Completed
    190
    203
    2
    Notes
    [7] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Milestone provided to define analysis population

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    KLU156 (Participants with ≥10 kg Body Weight)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Reporting group title
    Coartem (Participants with ≥10 kg Body Weight)
    Reporting group description
    		 Coartem twice a day (BID) for 3 days under fed conditions.

    Reporting group title
    KLU156 (Participants with <10 kg Body Weight)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Reporting group title
    Coartem (Participants with <10 kg Body Weight
    Reporting group description
    		 Coartem twice a day (BID) for 3 days under fed conditions.

    Reporting group values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight) KLU156 (Participants with <10 kg Body Weight) Coartem (Participants with <10 kg Body Weight Total
    Number of subjects
    		 836 832 24 28 1720
    Age Categorical
    Units: participants
        Infants and toddlers (28 days-23 months)
    		 13 9 18 14 54
        Children (2-11 years)
    		 506 515 6 14 1041
        Adolescents (12-17 years)
    		 162 152 0 0 314
        Adults (18-64 years)
    		 152 155 0 0 307
        From 65-84 years
    		 3 1 0 0 4
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.13 ( 10.46 ) 11.94 ( 9.91 ) 1.60 ( 0.47 ) 1.80 ( 0.60 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 419 395 15 14 843
        Male
    		 417 437 9 14 877
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 816 813 24 28 1681
        Race Not Reported
    		 19 19 0 0 38
        Race Unknown
    		 1 0 0 0 1
    Subject analysis sets

    Subject analysis set title
    Coartem (Participants with <10 kg Body Weight)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Coartem twice a day (BID) for 3 days under fed conditions.

    Subject analysis sets values
    		 Coartem (Participants with <10 kg Body Weight)
    Number of subjects
    27
    Age Categorical
    Units: participants
        Infants and toddlers (28 days-23 months)
    13
        Children (2-11 years)
    14
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    1.80 ( 0.60 )
    Sex: Female, Male
    Units: participants
        Female
    14
        Male
    13
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    27
        Race Not Reported
    0
        Race Unknown
    0

    End points

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    End points reporting groups
    Reporting group title
    KLU156 (Participants with ≥10 kg Body Weight)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Reporting group title
    Coartem (Participants with ≥10 kg Body Weight)
    Reporting group description
    		 Coartem twice a day (BID) for 3 days under fed conditions.

    Reporting group title
    KLU156 (Participants with <10 kg Body Weight)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Reporting group title
    Coartem (Participants with <10 kg Body Weight
    Reporting group description
    		 Coartem twice a day (BID) for 3 days under fed conditions.
    Reporting group title
    KLU156 (≥10 kg Body Weight Entering from Core KLU156 Arm)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Reporting group title
    KLU156 (≥10 kg Body Weight Entering from Core Coartem Arm)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Reporting group title
    KLU156 (<10 kg Body Weight Entering from Core KLU156 Arm)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal).

    Subject analysis set title
    Coartem (Participants with <10 kg Body Weight)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Coartem twice a day (BID) for 3 days under fed conditions.

    Primary: Core phase: PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29

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    End point title
    		 Core phase: PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 [1]
    End point description
    PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at Day 29 is defined as the percentage of participants who are clinically well and have no recrudescence (reappearance of the original malaria infection) by 29 days after treatment, with PCR genotyping used to distinguish new infections from recrudescence. This primary outcome was applicable to the non-US submission.
    End point type
    Primary
    End point timeframe
    Day 29 (i.e., 28 days post-first dose administration)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    657
    686
    Units: percentage of participants
        number (confidence interval 95%)
    97.4 (95.9 to 98.5)
    94.0 (92.0 to 95.7)
    Statistical analysis title
    		 Analysis
    Comparison groups
    KLU156 (Participants with ≥10 kg Body Weight) v Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects included in analysis
    1343
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    		 Wilson uncorrected method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 5.6
    Notes
    [2] - Non-inferiority of KLU156 versus Coartem was concluded if the lower limit of the 2-sided 95% CI was above the pre-defined -5% non-inferiority margin.

    Primary: Core phase: Uncorrected ACPR (US NDA Submission) at Day 29

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    End point title
    		 Core phase: Uncorrected ACPR (US NDA Submission) at Day 29 [3]
    End point description
    Uncorrected ACPR at Day 29 is defined as the percentage of participants who are clinically well and have no malaria parasite reappearance detected by Day 29 after treatment, without using parasite genotyping to distinguish new infections from recrudescence of the original infection. This primary outcome was applicable to US New Drug Application (NDA) submission.
    End point type
    Primary
    End point timeframe
    Day 29
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    726
    722
    Units: percentage of participants
        number (confidence interval 95%)
    85.3 (82.5 to 87.8)
    82.1 (79.1 to 84.9)
    Statistical analysis title
    		 Analysis
    Comparison groups
    KLU156 (Participants with ≥10 kg Body Weight) v Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects included in analysis
    1448
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    Method
    		 Wilson uncorrected method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 6.9
    Notes
    [4] - Non-inferiority of KLU156 versus Coartem was concluded if the lower limit of the 2-sided 95% CI was above the pre-defined -7.5% non-inferiority margin.

    Secondary: Core phase: PCR-corrected ACPR at Days 22 and 43

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    End point title
    		 Core phase: PCR-corrected ACPR at Days 22 and 43 [5]
    End point description
    To confirm the efficacy of KLU156 by assessing PCR-corrected ACPR at additional time points.
    End point type
    Secondary
    End point timeframe
    Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    664
    713
    Units: percentage of participants
    number (confidence interval 95%)
        Day 22 n=664,713
    98.9 (97.8 to 99.6)
    96.5 (94.9 to 97.7)
        Day 43/End of Core Phase n=626,627
    94.6 (92.5 to 96.2)
    91.7 (89.3 to 93.7)
    No statistical analyses for this end point

    Secondary: Core phase: Uncorrected ACPR at Days 22 and 43

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    End point title
    		 Core phase: Uncorrected ACPR at Days 22 and 43 [6]
    End point description
    To confirm the efficacy of KLU156 by assessing uncorrected ACPR at additional time points.
    End point type
    Secondary
    End point timeframe
    Days 22 and 43 (i.e., 21 and 42 days post-first dose administration)
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    726
    722
    Units: percentage of participants
    number (confidence interval 95%)
        Day 22 n=726,722
    90.1 (87.7 to 92.2)
    92.1 (89.9 to 94.0)
        Day 43/End of Core Phase n=726,722
    74.4 (71.0 to 77.5)
    72.6 (69.2 to 75.8)
    No statistical analyses for this end point

    Secondary: Core phase: Percentage of Participants With Recrudescence

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    End point title
    		 Core phase: Percentage of Participants With Recrudescence [7]
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Days 22, 29 and 43
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    667
    711
    Units: percentage of participants
        Day 8 to Day 22 n=667,711
    0
    6
        Day 23 to Day 29 n=658,680
    3
    15
        Day 30 to Day 43 n=626,615
    12
    5
    No statistical analyses for this end point

    Secondary: Core phase: Percentage of Participants With New Infection

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    End point title
    		 Core phase: Percentage of Participants With New Infection [8]
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Days 22, 29 and 43
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    667
    711
    Units: percentage of participants
        Day 8 to Day 22 n=667,711
    4
    19
        Day 23 to Day 29 n=657,674
    15
    46
        Day 30 to Day 43 n=625,608
    66
    64
    No statistical analyses for this end point

    Secondary: Core phase: Fever Clearance Time

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    End point title
    		 Core phase: Fever Clearance Time [9]
    End point description
    Fever clearance time 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.
    End point type
    Secondary
    End point timeframe
    Up to Day 3
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    726
    722
    Units: hours
        median (confidence interval 95%)
    6.3 (6.0 to 11.6)
    11.9 (11.4 to 12.0)
    No statistical analyses for this end point

    Secondary: Core phase: Parasite Clearance Time

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    End point title
    		 Core phase: Parasite Clearance Time [10]
    End point description
    Parasite clearance time 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.
    End point type
    Secondary
    End point timeframe
    Up to Day 3
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    726
    722
    Units: hours
        median (confidence interval 95%)
    37.6 (36.2 to 46.9)
    36.0 (35.9 to 36.0)
    No statistical analyses for this end point

    Secondary: Core phase: Gametocyte Clearance Time

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    End point title
    		 Core phase: Gametocyte Clearance Time [11]
    End point description
    To confirm the efficacy of KLU156 by assessing gametocyte clearance between the two treatment arms
    End point type
    Secondary
    End point timeframe
    Up to Day 3
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    726
    722
    Units: hours
        median (confidence interval 95%)
    35.9 (24.0 to 48.0)
    48.0 (36.0 to 159.7)
    No statistical analyses for this end point

    Secondary: Core phase: Percentage of Participants With Parasitemia

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    End point title
    		 Core phase: Percentage of Participants With Parasitemia [12]
    End point description
    For the parasitemia assessment, blood sampling can be done by means of a finger prick except when the timing for parasitology assessments coincides with time for clinical laboratory tests, in which case, blood sample can be taken from the venous blood collected for clinical laboratory analyses.
    End point type
    Secondary
    End point timeframe
    12, 24, 48 and 72 hours after treatment
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    724
    721
    Units: percentage of participants
    number (confidence interval 95%)
        12 Hours n=719,721
    96.9 (95.40 to 98.07)
    92.0 (89.72 to 93.84)
        24 Hours n=723,720
    86.3 (83.58 to 88.73)
    62.5 (58.85 to 66.05)
        48 Hours n=721,721
    15.0 (12.45 to 17.80)
    9.0 (7.03 to 11.35)
        72 Hours n=724,719
    0.8 (0.30 to 1.80)
    1.7 (0.87 to 2.90)
    No statistical analyses for this end point

    Secondary: Core phase: Clearance of Gametocytes in Participants With Gametocytemia at Baseline

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    End point title
    		 Core phase: Clearance of Gametocytes in Participants With Gametocytemia at Baseline [13]
    End point description
    Assessed by microscopy. Baseline was pre-first dose administration.
    End point type
    Secondary
    End point timeframe
    From baseline up to Day 43
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    726
    722
    Units: percentage of participants
    number (not applicable)
        Day 1: Present at 6 Hours
    4.4
    4.7
        Day 1: Absent at 6 Hours
    94.1
    95.3
        Day 1: Present at 12 Hours
    4.5
    4.7
        Day 1: Absent at 12 Hours
    94.5
    95.2
        Day 2: Present at 24 Hours
    3.9
    6.2
        Day 2: Absent at 24 Hours
    95.7
    93.5
        Day 2: Present at 36 Hours
    2.3
    3.6
        Day 2: Absent at 36 Hours
    97.2
    96.1
        Day 3: Present
    1.1
    98.8
        Day 3: Absent
    3.2
    96.7
        Day 4: Present
    1.0
    1.9
        Day 4: Absent
    98.8
    97.6
        Day 8: Present
    0.1
    1.8
        Day 8: Absent
    99.2
    97.0
        Day 22: Present
    0
    0.3
        Day 22: Absent
    93.5
    97.5
        Day 29: Present
    0
    0.1
        Day 29: Absent
    97.1
    97.1
        Day 43/End of Core Phase: Present
    0.1
    0.3
        Day 43/End of Core Phase: Absent
    97.2
    96.8
    No statistical analyses for this end point

    Secondary: Core phase: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and AEs of Grade 3 Severity or Higher

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    End point title
    		 Core phase: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and AEs of Grade 3 Severity or Higher [14]
    End point description
    Incidence and severity of TEAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs. Severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death).
    End point type
    Secondary
    End point timeframe
    Day 43
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    830
    831
    Units: percentage of participants
    number (not applicable)
        All TEAEs
    444
    422
        TEAEs of Grade 3 Severity or Higher
    2.5
    2.8
    No statistical analyses for this end point

    Secondary: Core phase: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs), Graded by Severity

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    End point title
    		 Core phase: Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs), Graded by Severity [15]
    End point description
    Incidence and severity of treatment-emergent SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs. Severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), and Grade 5 (Death).
    End point type
    Secondary
    End point timeframe
    Day 43
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight) Coartem (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    830
    831
    Units: percentage of participants
        Grade 2
    2
    5
        Grade 3
    5
    1
        Grade 4
    0
    2
    No statistical analyses for this end point

    Secondary: Extension phase: PCR-corrected ACPR

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    End point title
    		 Extension phase: PCR-corrected ACPR [16]
    End point description
    To evaluate PCR-corrected ACPR over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection). Patients were instructed to return to the study site whenever symptoms suggestive of malaria occurred. At each suspected malaria episode, eligibility for KLU156 treatment was reassessed, including confirmation of malaria diagnosis.
    End point type
    Secondary
    End point timeframe
    Up to Day 29 for each KLU156 treatment episode
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    342
    Units: percentage of participants
    number (confidence interval 95%)
        1st KLU156 Treatment n=342
    98.0 (95.8 to 99.2)
        2nd KLU156 Treatment n=214
    97.2 (94.0 to 99.0)
        3rd+KLU156 includes 3rd, 4th, 5th, 6th groups n=59
    100.0 (93.9 to 100.0)
    No statistical analyses for this end point

    Secondary: Extension Phase: Uncorrected ACPR

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    End point title
    		 Extension Phase: Uncorrected ACPR [17]
    End point description
    To evaluate uncorrected ACPR over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection).
    End point type
    Secondary
    End point timeframe
    Up to Day 29 for each KLU156 treatment episode
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    362
    Units: percentage of participants
    number (confidence interval 95%)
        1st KLU156 Treatment n=362
    86.5 (82.5 to 89.8)
        2nd KLU156 Treatment n=222
    87.4 (82.3 to 91.5)
        3rd+KLU156 includes 3rd, 4th, 5th, 6th groups n=59
    88.1 (77.1 to 95.1)
    No statistical analyses for this end point

    Secondary: Extension phase: Percentage of Participants With KLU156-related AEs by Malaria Episode

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    End point title
    		 Extension phase: Percentage of Participants With KLU156-related AEs by Malaria Episode [18]
    End point description
    To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection).
    End point type
    Secondary
    End point timeframe
    Up to approximately 18 months
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    393
    Units: percentage of participants
    number (not applicable)
        1st KLU156 Treatment n=393
    12.2
        2nd KLU156 Treatment n=230
    9.1
        3rd+KLU156 includes 3rd, 4th, 5th, 6th groups n=62
    11.3
    No statistical analyses for this end point

    Secondary: Extension phase: Percentage of Participants With SAEs by Severity and Malaria Episode

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    End point title
    		 Extension phase: Percentage of Participants With SAEs by Severity and Malaria Episode [19]
    End point description
    To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 10 kg of body weight suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection).
    End point type
    Secondary
    End point timeframe
    Up to approximately 18 months
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    393
    Units: percentage of participants
        1st KLU156 Treatment n=393
    0
        2nd KLU156 Treatment n=230
    0
        3rd+KLU156 includes 3rd, 4th, 5th, 6th groups n=62
    0
    No statistical analyses for this end point

    Secondary: Extension phase: Gametocyte Carriage Over Time

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    End point title
    		 Extension phase: Gametocyte Carriage Over Time [20]
    End point description
    To assess gametocyte carriage over time by malaria episode in the extension phase
    End point type
    Secondary
    End point timeframe
    Up to Day 29 for each KLU156 treatment episode
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Protocol amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses.
    End point values
    		 KLU156 (Participants with ≥10 kg Body Weight)
    Number of subjects analysed
    362
    Units: percentage of participants
    number (not applicable)
        1st KLU156 Treatment, Present at Day 3 n=362
    1.1
        1st KLU156 Treatment, Absent at Day 3 n=362
    98.9
        2nd KLU156 Treatment Present at Day 3 n=222
    0.5
        2nd KLU156 Treatment Absent at Day 3 n=222
    99.1
        3rd+KLU156 Groups 3, 4, 5, 6 Pres. at Day 3 n=59
    0
        3rd+KLU156 Groups 3, 4, 5, 6 Abs. at Day 3 n=59
    100
        1st KLU156 Treatment, Present at Day 4 n=362
    0.8
        1st KLU156 Treatment, Absent at Day 4 n=362
    98.9
        2nd KLU156 Treatment Present at Day 4 n=222
    0
        2nd KLU156 Treatment Absent at Day 4 n=222
    100
        3rd+KLU156 Groups 3, 4, 5, 6 Pres. at Day 4 n=59
    0
        3rd+KLU156 Groups 3, 4, 5, 6 Abs. at Day 4 n=59
    100
        1st KLU156 Treatment, Present at Day 8 n=362
    0
        1st KLU156 Treatment, Absent at Day 8 n=362
    99.4
        2nd KLU156 Treatment Present at Day 8 n=222
    0
        2nd KLU156 Treatment Absent at Day 8 n=222
    100
        3rd+KLU156 Groups 3, 4, 5, 6 Pres. at Day 8 n=59
    0
        3rd+KLU156 Groups 3, 4, 5, 6 Abs. at Day 8 n=59
    100
        1st KLU156 Treatment, Present at Day 29 n=362
    0
        1st KLU156 Treatment, Absent at Day 29 n=362
    98.9
        2nd KLU156 Treatment Present at Day 29 n=222
    0
        2nd KLU156 Treatment Absent at Day 29 n=222
    99.1
        3rd+KLU156 Groups 3, 4, 5, 6 Pres. at Day 29 n=59
    0
        3rd+KLU156 Groups 3, 4, 5, 6 Abs. at Day 29 n=59
    100
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from the first dose of study treatment until the end of study treatment plus a follow-up period, up to a maximum of approximately 20 months.
    Adverse event reporting additional description
    The safety set included all participants who took at least one dose of study drug during the treatment period of the study. Safety data are reported for all treated patients, regardless of body weight.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.1
    Reporting groups
    Reporting group title
    Core Phase:@KLU156
    Reporting group description
    		 Core Phase:@KLU156

    Reporting group title
    Core Phase:@Coartem
    Reporting group description
    		 Core Phase:@Coartem

    Reporting group title
    Extension KLU156 (Entering from Core Phase Coartem Arm)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal) in extension.

    Reporting group title
    Extension KLU156 (Entering from Core Phase KLU156 Arm)
    Reporting group description
    		 KLU156 once daily (QD) for 3 days under fed conditions (light meal) in extension.

    Reporting group title
    Extension@Phase:@Total
    Reporting group description
    		 Extension@Phase:@Total

    Reporting group title
    Core Phase:@Total
    Reporting group description
    		 Core Phase:@Total

    Serious adverse events
    		 Core Phase:@KLU156 Core Phase:@Coartem Extension KLU156 (Entering from Core Phase Coartem Arm) Extension KLU156 (Entering from Core Phase KLU156 Arm) Extension@Phase:@Total Core Phase:@Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 854 (1.05%)
    10 / 858 (1.17%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    19 / 1712 (1.11%)
         number of deaths (all causes)
    0
    1
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 854 (0.00%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    0 / 854 (0.00%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Lower limb fracture
         subjects affected / exposed
    0 / 854 (0.00%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Snake bite
         subjects affected / exposed
    0 / 854 (0.00%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 854 (0.35%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    4 / 1712 (0.23%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intussusception
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis viral
         subjects affected / exposed
    0 / 854 (0.00%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaria
         subjects affected / exposed
    0 / 854 (0.00%)
    2 / 858 (0.23%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    2 / 1712 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 854 (0.00%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 854 (0.12%)
    1 / 858 (0.12%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    2 / 1712 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 854 (0.12%)
    0 / 858 (0.00%)
    0 / 203 (0.00%)
    0 / 192 (0.00%)
    0 / 395 (0.00%)
    1 / 1712 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Core Phase:@KLU156 Core Phase:@Coartem Extension KLU156 (Entering from Core Phase Coartem Arm) Extension KLU156 (Entering from Core Phase KLU156 Arm) Extension@Phase:@Total Core Phase:@Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    358 / 854 (41.92%)
    319 / 858 (37.18%)
    52 / 203 (25.62%)
    55 / 192 (28.65%)
    107 / 395 (27.09%)
    677 / 1712 (39.54%)
    Investigations
    Electrocardiogram QT prolonged
         subjects affected / exposed
    22 / 854 (2.58%)
    8 / 858 (0.93%)
    6 / 203 (2.96%)
    10 / 192 (5.21%)
    16 / 395 (4.05%)
    30 / 1712 (1.75%)
         occurrences all number
    24
    9
    6
    11
    17
    33
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    72 / 854 (8.43%)
    72 / 858 (8.39%)
    10 / 203 (4.93%)
    9 / 192 (4.69%)
    19 / 395 (4.81%)
    144 / 1712 (8.41%)
         occurrences all number
    74
    74
    10
    11
    21
    148
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    80 / 854 (9.37%)
    108 / 858 (12.59%)
    10 / 203 (4.93%)
    10 / 192 (5.21%)
    20 / 395 (5.06%)
    188 / 1712 (10.98%)
         occurrences all number
    81
    117
    10
    11
    21
    198
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    170 / 854 (19.91%)
    39 / 858 (4.55%)
    16 / 203 (7.88%)
    21 / 192 (10.94%)
    37 / 395 (9.37%)
    209 / 1712 (12.21%)
         occurrences all number
    171
    39
    17
    22
    39
    210
    Infections and infestations
    Malaria
         subjects affected / exposed
    136 / 854 (15.93%)
    197 / 858 (22.96%)
    21 / 203 (10.34%)
    23 / 192 (11.98%)
    44 / 395 (11.14%)
    333 / 1712 (19.45%)
         occurrences all number
    138
    203
    21
    24
    45
    341

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 May 2025
    This amendment increased the minimum body weight requirement for study participation from ≥ 5 kg to ≥ 10 kg and revised the statistical analysis plan to exclude patients < 10 kg from the main analyses due to palatability issues of the formulation (vomiting/spitting out the study medication) observed in children < 10 kg. Additional protocol updates included the addition of gametocyte clearance time by microscopy as a secondary endpoint, clarification of the limit of total allowable blood volume collected during the study, definition of Hy's Law, guidance for potential cases to be reported as serious adverse events, and addition of analyses for patients < 10 kg.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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