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    Clinical Trial Results:
    A Phase 2 interventional, multicenter, randomized, open-label study in three age-descending cohorts to evaluate efficacy, safety and tolerability of KAF156 and Lumefantrine-SDF combination in the treatment of acute uncomplicated Plasmodium falciparum Malaria in a pediatric population

    Summary
    EudraCT number
    		 2021-003583-27
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    28 Aug 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Mar 2025
    First version publication date
    15 Mar 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CKAF156A2203
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04546633
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharmaceuticals
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Aug 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Aug 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of KAF156 combined with LUM- Solid dispersion formulation (SDF) compared to Coartem® (non-inferiority trial) for the treatment of uncomplicated malaria caused by P. falciparum in children 6 months to < 12 years.
    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
    16 Feb 2021
    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: 59
    Country: Number of subjects enrolled
    Congo, The Democratic Republic of the: 1
    Country: Number of subjects enrolled
    Gabon: 92
    Country: Number of subjects enrolled
    Mali: 132
    Country: Number of subjects enrolled
    Côte d’Ivoire: 11
    Worldwide total number of subjects
    295
    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)
    80
    Children (2-11 years)
    140
    Adolescents (12-17 years)
    75
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants took part in 10 investigative sites in 5 countries.

    Pre-assignment
    Screening details
    		 During pre-screening, a P. falciparum parasite count was obtained for all patients. Further screening assessments took place only if the outcome was in the pre-defined range (≥ 1,000 and ≤ 150,000 parasites/µL in Run-In Cohort and ≥ 1,500 and ≤ 150,000 parasites/µL in Cohort 1 and Cohort 2).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed
    Arm description
    		 KAF156-400 mg and LUM-240 mg-solid dispersion formulation (SDF), once daily (QD) for 2 days in fed condition, via oral.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumefantrine Solid Dispersion Formulation
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with KAF156 once daily for 2 days in fed condition at 240mg.

    Investigational medicinal product name
    KAF156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with LUM-SDF once daily for 2 days in fed condition at 400mg.

    Arm title
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted
    Arm description
    		 KAF156-400 mg and LUM-240 mg-SDF once daily for 2 days in fasted condition, via oral.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumefantrine Solid Dispersion Formulation
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with KAF156 once daily for 2 days in fasted condition at 240mg.

    Investigational medicinal product name
    KAF156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with LUM-SDF once daily for 2 days in fasted condition at 400mg.

    Arm title
    		 Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed
    Arm description
    		 KAF156-400 mg and LUM-480 mg-SDF once daily for 2 days in fed condition, via oral.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumefantrine Solid Dispersion Formulation
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with KAF156 once daily for 2 days in fed condition at 480mg.

    Investigational medicinal product name
    KAF156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with LUM-SDF once daily for 2 days in fed condition at 400mg.

    Arm title
    		 Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted
    Arm description
    		 KAF156-400 mg and LUM-480 mg-SDF once daily for 2 days in fasted condition, via oral.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumefantrine Solid Dispersion Formulation
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with KAF156 once daily for 2 days in fasted condition at 480mg.

    Investigational medicinal product name
    KAF156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with LUM-SDF once daily for 2 days in fasted condition at 400mg.

    Arm title
    		 Cohort 1/2-KAF400mg/LUM480mg-QDx3
    Arm description
    		 KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumefantrine Solid Dispersion Formulation
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with KAF156 once daily for 3 days with a light meal and the full dose was adjusted based on patient´s body weight.

    Investigational medicinal product name
    KAF156
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered in combination with LUM-SDF once daily for 3 days with a light meal and the full dose was adjusted based on patient´s body weight.

    Arm title
    		 Cohort 1/2-Artemether80mg/LUM480mg
    Arm description
    		 Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Artemether80mg/LUM480mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Dispersible tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered with food and the doses were based on patient’s body weight as per product label, twice daily for 3 days.

    Number of subjects in period 1
    		Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Started
    25
    26
    11
    13
    110
    110
    Completed
    23
    26
    11
    13
    104
    102
    Not completed
    2
    0
    0
    0
    6
    8
         Lost to follow-up
    1
    -
    -
    -
    4
    4
         Guardian decision
    1
    -
    -
    -
    2
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed
    Reporting group description
    		 KAF156-400 mg and LUM-240 mg-solid dispersion formulation (SDF), once daily (QD) for 2 days in fed condition, via oral.

    Reporting group title
    Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted
    Reporting group description
    		 KAF156-400 mg and LUM-240 mg-SDF once daily for 2 days in fasted condition, via oral.

    Reporting group title
    Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed
    Reporting group description
    		 KAF156-400 mg and LUM-480 mg-SDF once daily for 2 days in fed condition, via oral.

    Reporting group title
    Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted
    Reporting group description
    		 KAF156-400 mg and LUM-480 mg-SDF once daily for 2 days in fasted condition, via oral.

    Reporting group title
    Cohort 1/2-KAF400mg/LUM480mg-QDx3
    Reporting group description
    		 KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight.

    Reporting group title
    Cohort 1/2-Artemether80mg/LUM480mg
    Reporting group description
    		 Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label.

    Reporting group values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg Total
    Number of subjects
    		 25 26 11 13 110 110 295
    Age Categorical
    Units:
        <=18 years
    		 25 26 11 13 110 110 295
        Between 18 and 65 years
    		 0 0 0 0 0 0 0
        >=65 years
    		 0 0 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 14.08 ( 1.382 ) 13.62 ( 1.416 ) 14.36 ( 1.859 ) 14.85 ( 1.573 ) 4.86 ( 3.464 ) 4.58 ( 3.251 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 15 12 8 4 60 42 141
        Male
    		 10 14 3 9 50 68 154
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 25 26 11 13 110 110 295
    Subject analysis sets

    Subject analysis set title
    Cohort 1-KAF400mg/LUM480mg-QDx3
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 2-KAF400mg/LUM480mg-QDx3
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis set title
    Cohort 1-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 2-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis set title
    Cohort 2-KAF400mg/LUM480mg-QDx3Edit
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis set title
    Cohort 1-KAF400mg/LUM480mg-QDx3
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 1-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 2-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis sets values
    		 Cohort 1-KAF400mg/LUM480mg-QDx3 Cohort 2-KAF400mg/LUM480mg-QDx3 Cohort 1-Artemether80mg/LUM480mg Cohort 2-Artemether80mg/LUM480mg Cohort 2-KAF400mg/LUM480mg-QDx3Edit Cohort 1-KAF400mg/LUM480mg-QDx3 Cohort 1-Artemether80mg/LUM480mg Cohort 2-Artemether80mg/LUM480mg
    Number of subjects
    65
    31
    53
    31
    31
    68
    65
    35
    Age Categorical
    Units:
        <=18 years
        Between 18 and 65 years
        >=65 years
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Sex: Female, Male
    Units: participants
        Female
        Male
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    65
    31
    53
    31
    31
    68
    65
    35

    End points

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    End points reporting groups
    Reporting group title
    Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed
    Reporting group description
    		 KAF156-400 mg and LUM-240 mg-solid dispersion formulation (SDF), once daily (QD) for 2 days in fed condition, via oral.

    Reporting group title
    Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted
    Reporting group description
    		 KAF156-400 mg and LUM-240 mg-SDF once daily for 2 days in fasted condition, via oral.

    Reporting group title
    Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed
    Reporting group description
    		 KAF156-400 mg and LUM-480 mg-SDF once daily for 2 days in fed condition, via oral.

    Reporting group title
    Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted
    Reporting group description
    		 KAF156-400 mg and LUM-480 mg-SDF once daily for 2 days in fasted condition, via oral.

    Reporting group title
    Cohort 1/2-KAF400mg/LUM480mg-QDx3
    Reporting group description
    		 KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight.

    Reporting group title
    Cohort 1/2-Artemether80mg/LUM480mg
    Reporting group description
    		 Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label.

    Subject analysis set title
    Cohort 1-KAF400mg/LUM480mg-QDx3
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 2-KAF400mg/LUM480mg-QDx3
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis set title
    Cohort 1-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 2-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis set title
    Cohort 2-KAF400mg/LUM480mg-QDx3Edit
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 2 participants ages 6 months to <2 years.

    Subject analysis set title
    Cohort 1-KAF400mg/LUM480mg-QDx3
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    KAF156-400mg and LUM-480 mg-SDF once daily for 3 days, via oral. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 1-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 1 participants age 2 to <12 years.

    Subject analysis set title
    Cohort 2-Artemether80mg/LUM480mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Artemether-80mg/LUM-480 mg, twice daily for 3 days, it was administered with food and the doses were based on patient’s body weight as per product label. Cohort 2 participants ages 6 months to <2 years.

    Primary: Polymerase Chain Reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) - Cohorts 1 and 2 pooled

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    End point title
    		 Polymerase Chain Reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) - Cohorts 1 and 2 pooled [1]
    End point description
    PCR-corrected ACPR, defined as the absence of parasitemia(PS),was evaluated on Day29. 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 Day29 if the participant did not meet any of the criteria of early treatment failure (up to Day4), late clinical failure(Day5 to Day29) or late parasitological failure(Day8 to Day29), and had absence of PS on Day29 irrespective of axillary temperature unless the presence of PS after 7days(Day8 or later) was due to reinfection based on PCR genotyping.A presence of PS after 7days of treatment initiation was considered as a reinfection only if the PS was clear before Day8 and none of the parasite strain(s) detected on Day8 or later match with the parasite strain at baseline based on PCR genotyping.Given the age-independent symptoms of acute malaria, and to increase statistical power,the cohorts 1 and 2 were pooled.
    End point type
    Primary
    End point timeframe
    Day 29
    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: This Endpoint is not analyzed for all arms
    End point values
    		 Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    98
    99
    Units: Percentage of participants
        number (confidence interval 95%)
    99.0 (94.4 to 100.0)
    99.0 (94.5 to 100.0)
    Statistical analysis title
    		 PCR-ACPR
    Comparison groups
    Cohort 1/2-KAF400mg/LUM480mg-QDx3 v Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects included in analysis
    197
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 2.8
    Notes
    [2] - Non-inferiority was concluded if the lower limit of the 2-sided 95% CI was above the pre-defined -10% non-inferiority margin.

    Secondary: PCR-corrected and uncorrected Adequate Clinical and Parasitological Response (ACPR)

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    End point title
    		 PCR-corrected and uncorrected Adequate Clinical and Parasitological Response (ACPR)
    End point description
    PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and had absence of parasitemia on Days 15, 29 or 43 irrespective of axillary temperature unless the presence of parasitemia after 7 days was due to reinfection based on PCR. A presence of parasitemia after 7 days of treatment initiation was considered as a reinfection only if the parasitemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    Corrected ACPR: Day 15, Day 43; Uncorrected ACPR: Day 15, Day 29 and Day 43
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    11
    22
    8
    13
    98
    99
    Units: Percentage of participants
    number (confidence interval 95%)
        Day 15-corrected ACPR
    100.0 (71.5 to 100.0)
    100.0 (84.6 to 100.0)
    100.0 (63.1 to 100.0)
    100.0 (75.3 to 100.0)
    100.0 (96.3 to 100.0)
    100.0 (96.3 to 100.0)
        Day 43-corrected ACPR
    100.0 (71.5 to 100.0)
    100.0 (84.6 to 100.0)
    87.5 (47.3 to 99.7)
    92.3 (64.0 to 99.8)
    94.9 (88.5 to 98.3)
    96.0 (90.0 to 98.9)
        Day 15-uncorrected ACPR
    100.0 (71.5 to 100.0)
    100.0 (84.6 to 100.0)
    100.0 (63.1 to 100.0)
    100.0 (75.3 to 100.0)
    100.0 (96.3 to 100.0)
    100.0 (96.3 to 100.0)
        Day 29-uncorrected ACPR
    90.9 (58.7 to 99.8)
    95.5 (77.2 to 99.9)
    87.5 (47.3 to 99.7)
    100.0 (75.3 to 100.0)
    96.9 (91.3 to 99.4)
    94.9 (88.6 to 98.3)
        Day 43-uncorrected ACPR
    81.8 (48.2 to 97.7)
    86.4 (65.1 to 97.1)
    62.5 (24.5 to 91.5)
    76.9 (46.2 to 95.0)
    85.7 (77.2 to 92.0)
    85.9 (77.4 to 92.0)
    No statistical analyses for this end point

    Secondary: PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - Run-in Cohort

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    End point title
    		 PCR-corrected Adequate Clinical and Parasitological Response (ACPR) - Run-in Cohort [3]
    End point description
    PCR-corrected ACPR, defined as the absence of parasitemia, was evaluated on Day 29. Microscopic species identification was confirmed and determined by polymerase chain reaction (PCR) genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR corrected ACPR at Day 29 if the participant did not meet any of the criteria of early treatment failure (ETF) (up to Day 4), late clinical failure (LCF) (Day 5 to Day 29) or late parasitological failure (LPF) (Day 8 to Day 29), and had absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days (Day 8 or later) was due to reinfection based on PCR genotyping. 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 match with the parasite strain at baseline based on PCR genotyping.
    End point type
    Secondary
    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: This Endpoint is not analyzed for all arms
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted
    Number of subjects analysed
    11
    22
    8
    13
    Units: Percentage of participants
        number (confidence interval 95%)
    100.0 (71.5 to 100.0)
    100.0 (84.6 to 100.0)
    100.0 (63.1 to 100.0)
    100.0 (75.3 to 100.0)
    No statistical analyses for this end point

    Secondary: Parasite Clearance Time (PCT)

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    End point title
    		 Parasite Clearance Time (PCT)
    End point description
    PCT is defined as time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. PCT is based on uncorrected parasite counts. PCT was calculated using the Kaplan-Meier method. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    up to 43 days
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    25
    26
    11
    13
    110
    110
    Units: hours
        median (confidence interval 95%)
    48.1 (36.1 to 48.2)
    36.2 (36.0 to 71.9)
    48.0 (36.0 to 48.2)
    48.0 (24.0 to 48.2)
    47.5 (36.2 to 47.8)
    35.9 (35.6 to 36.0)
    No statistical analyses for this end point

    Secondary: Fever clearance Times (FCT)

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    End point title
    		 Fever clearance Times (FCT)
    End point description
    FCT is defined as time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. FCT was calculated using the Kaplan-Meier method. Participants who received any antimalarial medication (including rescue medication) before fever clearance are censored at the first use of antimalarial medication. Participants without fever clearance are censored at the time of last fever assessment. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2). Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    up to 43 days
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    3
    5
    3
    2
    33
    36
    Units: hours
        median (confidence interval 95%)
    23.5 (23.3 to 999)
    23.9 (23.6 to 999)
    23.8 (23.7 to 999)
    27.1 (23.9 to 999)
    23.9 (23.4 to 24.3)
    23.7 (23.5 to 23.9)
    No statistical analyses for this end point

    Secondary: Percentage Early Treatment Failure (ETF)

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    End point title
    		 Percentage Early Treatment Failure (ETF)
    End point description
    Participants were defined as early treatment failures (ETFs) if they developed danger signs or severe malaria on Day 2, Day 3, or Day 4 in the presence of parasitemia, parasitemia on Day 3 with a count higher than the Day 1 count irrespective of axillary temperature, parasitemia on Day 4 with axillary temperature ≥ 37.5°C, or parasitemia on Day 4 with a count equal to or more than 25% of the count on Day 1. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    From Day 1 to Day 4
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    24
    26
    11
    13
    108
    110
    Units: Percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 14.3)
    0.0 (0.0 to 13.2)
    0.0 (0.0 to 28.5)
    0.0 (0.0 to 24.7)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 3.3)
    No statistical analyses for this end point

    Secondary: Percentage Late Clinical Failure (LCF)

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    End point title
    		 Percentage Late Clinical Failure (LCF)
    End point description
    Participants were defined as late clinical failures (LCFs) if they developed danger signs or severe malaria on any day from Day 5 to Day 43 in the presence of parasitemia without previously meeting any of the criteria of ETF, or if they had parasitemia and an axillary temperature of ≥ 37.5°C on any day from Day 5 to Day 43 without previously meeting any of the criteria of ETF. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    Day 5 to Day 43
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    23
    26
    11
    13
    104
    102
    Units: Percentage of participants
        number (confidence interval 95%)
    8.7 (1.1 to 28.0)
    0.0 (0.0 to 13.2)
    0.0 (0.0 to 28.5)
    7.7 (0.2 to 36.0)
    8.7 (4.0 to 15.8)
    3.9 (1.1 to 9.7)
    No statistical analyses for this end point

    Secondary: Percentage Late Parasitological Failure (LPF)

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    End point title
    		 Percentage Late Parasitological Failure (LPF)
    End point description
    Participants were defined as late parasitological failures (LPFs) if they had parasitemia on any day from Day 8 to Day 43 and an axillary temperature < 37.5°C without previously meeting any of the criteria of ETF or LCF. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    Day 8 to Day 43
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    21
    26
    11
    12
    95
    98
    Units: Percentage of participants
        number (confidence interval 95%)
    19.0 (5.5 to 41.9)
    19.2 (6.6 to 39.4)
    54.5 (23.4 to 83.3)
    16.7 (2.1 to 48.4)
    4.2 (1.2 to 10.4)
    11.2 (5.7 to 19.2)
    No statistical analyses for this end point

    Secondary: Number of participants with recrudescence events

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    End point title
    		 Number of participants with recrudescence events
    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. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    Day 15, Day 29 and Day 43
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    25
    26
    11
    13
    110
    110
    Units: participants
        Day 15
    0
    0
    0
    0
    0
    0
        Day 29
    1
    0
    0
    0
    1
    1
        Day 43
    1
    0
    0
    1
    1
    1
    No statistical analyses for this end point

    Secondary: Number of participants with new infections events

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    End point title
    		 Number of participants with new infections events
    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. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    Day 15, Day 29 and Day 43
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    25
    26
    11
    13
    110
    110
    Units: participants
        Day 15
    0
    0
    0
    0
    0
    0
        Day 29
    1
    0
    2
    0
    3
    4
        Day 43
    3
    3
    3
    2
    7
    5
    No statistical analyses for this end point

    Secondary: Number of participants with treatment emergent adverse events (AEs) and serious adverse events (SAEs)

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    End point title
    		 Number of participants with treatment emergent adverse events (AEs) and serious adverse events (SAEs)
    End point description
    Number of participants with treatment emergent adverse events (any AE regardless of seriousness), and SAEs. Given the age-independent symptoms of acute malaria, and to increase statistical power, the cohorts 1 and 2 were pooled (cohort 1/2).
    End point type
    Secondary
    End point timeframe
    Adverse events were reported from first dose of study treatment until end of study treatment up to a maximum duration of approximately 43 days.
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1/2-KAF400mg/LUM480mg-QDx3 Cohort 1/2-Artemether80mg/LUM480mg
    Number of subjects analysed
    25
    26
    11
    13
    110
    110
    Units: participants
        Adverse Events
    15
    13
    10
    9
    74
    61
        Serious Adverse Events
    1
    0
    0
    1
    0
    4
    No statistical analyses for this end point

    Secondary: KAF156 and Lumefantrine (LUM) Cmax

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    End point title
    		 KAF156 and Lumefantrine (LUM) Cmax [4]
    End point description
    Cmax is the maximum observed plasma concentration following drug administration. PK parameters are calculated from plasma concentration-time data using non-compartmental methods. Analyte KAF156 is not applicable for Artemether80mg/LUM480mg arm. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    Run-in Cohort:Pre-dose,1,3,4,5,6,8,24,25,27,28,29,30,32,48,72,168 hours; PK sampling 6-12 years: 3,6,24,48,51,54,72,168 hours; 6 months -< 6 years: 24,48,51,54,72,168 hours; Coartem arm:24,48,68,168 hours.
    Notes
    [4] - 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: PK Endpoint not analyzed for participants on placebo
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1-KAF400mg/LUM480mg-QDx3 Cohort 2-KAF400mg/LUM480mg-QDx3 Cohort 1-Artemether80mg/LUM480mg Cohort 2-Artemether80mg/LUM480mg
    Number of subjects analysed
    11
    23
    8
    13
    65
    31
    53
    31
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        KAF156
    1520 ( 27.1 )
    1460 ( 26.5 )
    1610 ( 17.7 )
    1320 ( 24.6 )
    1240 ( 60.4 )
    741 ( 56.6 )
    999 ( 999 )
    999 ( 999 )
        LUM
    11600 ( 59.1 )
    7850 ( 64.4 )
    25900 ( 51.1 )
    10900 ( 86.7 )
    21300 ( 52.5 )
    9020 ( 135.5 )
    6510 ( 63.3 )
    3300 ( 142 )
    No statistical analyses for this end point

    Secondary: KAF156 and Lumefantrine Area under plasma concentration-time curve from time zero to the last measurable concentration sampling time (AUClast)

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    End point title
    		 KAF156 and Lumefantrine Area under plasma concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) [5]
    End point description
    AUC is the area under the plasma concentration-time curve. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. For Cohort 1/2 -Artemether80mg/LUM480mg arms enough plasma samples were not collected to calculate AUC parameters.
    End point type
    Secondary
    End point timeframe
    Run-in Cohort:Pre-dose,1,3,4,5,6,8,24,25,27,28,29,30,32,48,72,168 hours; PK sampling 6-12 years: 3,6,24,48,51,54,72,168 hours; 6 months -< 6 years: 24,48,51,54,72,168 hours; Coartem arm:24,48,68,168 hours.
    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: PK Endpoint not analyzed for participants on placebo
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1-KAF400mg/LUM480mg-QDx3 Cohort 2-KAF400mg/LUM480mg-QDx3Edit
    Number of subjects analysed
    11
    23
    8
    13
    65
    31
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        KAF156
    45900 ( 21.2 )
    44100 ( 30.7 )
    53000 ( 29.1 )
    44000 ( 27.4 )
    44100 ( 66.8 )
    25600 ( 71.6 )
        LUM
    389000 ( 60.4 )
    207000 ( 86.5 )
    934000 ( 49.7 )
    342000 ( 80.3 )
    970000 ( 59.6 )
    383000 ( 182.1 )
    No statistical analyses for this end point

    Secondary: KAF156 and Lumefantrine time to reach the maximum plasma concentration after drug administration (Tmax)

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    End point title
    		 KAF156 and Lumefantrine time to reach the maximum plasma concentration after drug administration (Tmax) [6]
    End point description
    Tmax is the time to reach maximum plasma concentration following drug administration. PK parameters are calculated from plasma concentration-time data using non-compartmental methods. For Cohort 1/2 -Artemether80mg/LUM480mg arms enough plasma samples were not collected to calculate Tmax parameter.
    End point type
    Secondary
    End point timeframe
    Run-in Cohort:Pre-dose,1,3,4,5,6,8,24,25,27,28,29,30,32,48,72,168 hours; PK sampling 6-12 years: 3,6,24,48,51,54,72,168 hours; 6 months -< 6 years: 24,48,51,54,72,168 hours; Coartem arm:24,48,68,168 hours.
    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: PK Endpoint not analyzed for participants on placebo
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 1-KAF400mg/LUM480mg-QDx3 Cohort 2-KAF400mg/LUM480mg-QDx3
    Number of subjects analysed
    11
    23
    8
    13
    65
    31
    Units: hours
    median (full range (min-max))
        KAF156
    3.92 (2.65 to 7.93)
    3.58 (1.35 to 5.88)
    4.46 (3.87 to 5.97)
    4.18 (2.85 to 7.98)
    3.03 (0 to 23.5)
    2.95 (0 to 23.5)
        LUM
    7.67 (4.02 to 8.12)
    7.7 (0.967 to 8.23)
    7.02 (5.9 to 24.1)
    6.05 (5.05 to 24.2)
    5.97 (0 to 23.9)
    6.02 (0 to 24.4)
    No statistical analyses for this end point

    Secondary: KAF156 and Lumefantrine plasma drug concentration 168 hours post first dose administration (C168h)

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    End point title
    		 KAF156 and Lumefantrine plasma drug concentration 168 hours post first dose administration (C168h) [7]
    End point description
    C168h is the plasma concentration at 168h post first dose administration. PK parameters are calculated from plasma concentration-time data using non-compartmental methods. Analyte KAF156 is not applicable for Artemether80mg/LUM480mg arm. Due to EudraCT system limitations, data fields in the table cannot contain letters (eg. NA indicating ‘not applicable’). Therefore, not applicable values are indicated as ‘999’.
    End point type
    Secondary
    End point timeframe
    at 168 hours
    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: PK Endpoint not analyzed for participants on placebo
    End point values
    		 Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM240mg-QDx2-Fasted Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fed Run-in Cohort-KAF400mg/LUM480mg-QDx2-Fasted Cohort 2-KAF400mg/LUM480mg-QDx3 Cohort 1-KAF400mg/LUM480mg-QDx3 Cohort 1-Artemether80mg/LUM480mg Cohort 2-Artemether80mg/LUM480mg
    Number of subjects analysed
    11
    23
    8
    13
    31
    68
    65
    35
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        KAF156
    23.9 ( 38.7 )
    21.8 ( 62.5 )
    14.9 ( 62.7 )
    25.3 ( 55.9 )
    11 ( 87.5 )
    24.8 ( 120.8 )
    999 ( 999 )
    999 ( 999 )
        LUM
    429 ( 50.1 )
    189 ( 106.1 )
    679 ( 36.5 )
    332 ( 73.5 )
    574 ( 135.8 )
    1320 ( 92.4 )
    438 ( 80.9 )
    297 ( 89.1 )
    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 first dose of study treatment until end of study treatment up to a maximum duration of approximately 43 days.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    KAF400mg/LUM240mg-QDx2-Fed
    Reporting group description
    		 KAF400mg/LUM240mg-QDx2-Fed

    Reporting group title
    Coartem
    Reporting group description
    		 Coartem

    Reporting group title
    KAF400mg/LUM480mg-QDx2-Fasted
    Reporting group description
    		 KAF400mg/LUM480mg-QDx2-Fasted

    Reporting group title
    KAF400mg/LUM480mg-QDx3
    Reporting group description
    		 KAF400mg/LUM480mg-QDx3

    Reporting group title
    KAF400mg/LUM240mg-QDx2-Fasted
    Reporting group description
    		 KAF400mg/LUM240mg-QDx2-Fasted

    Reporting group title
    KAF400mg/LUM480mg-QDx2-Fed
    Reporting group description
    		 KAF400mg/LUM480mg-QDx2-Fed

    Serious adverse events
    		 KAF400mg/LUM240mg-QDx2-Fed Coartem KAF400mg/LUM480mg-QDx2-Fasted KAF400mg/LUM480mg-QDx3 KAF400mg/LUM240mg-QDx2-Fasted KAF400mg/LUM480mg-QDx2-Fed
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 25 (4.00%)
    4 / 110 (3.64%)
    1 / 13 (7.69%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Investigations
    Liver function test increased
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 110 (1.82%)
    0 / 13 (0.00%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 25 (4.00%)
    1 / 110 (0.91%)
    1 / 13 (7.69%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 110 (0.91%)
    0 / 13 (0.00%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         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
    		 KAF400mg/LUM240mg-QDx2-Fed Coartem KAF400mg/LUM480mg-QDx2-Fasted KAF400mg/LUM480mg-QDx3 KAF400mg/LUM240mg-QDx2-Fasted KAF400mg/LUM480mg-QDx2-Fed
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 25 (48.00%)
    55 / 110 (50.00%)
    9 / 13 (69.23%)
    69 / 110 (62.73%)
    12 / 26 (46.15%)
    10 / 11 (90.91%)
    Investigations
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    0 / 13 (0.00%)
    1 / 110 (0.91%)
    0 / 26 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    1 / 13 (7.69%)
    0 / 110 (0.00%)
    1 / 26 (3.85%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    2 / 25 (8.00%)
    0 / 110 (0.00%)
    0 / 13 (0.00%)
    1 / 110 (0.91%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    3 / 25 (12.00%)
    6 / 110 (5.45%)
    1 / 13 (7.69%)
    18 / 110 (16.36%)
    1 / 26 (3.85%)
    4 / 11 (36.36%)
         occurrences all number
    3
    6
    1
    18
    1
    6
    Heart rate decreased
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    1 / 13 (7.69%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 25 (8.00%)
    1 / 110 (0.91%)
    3 / 13 (23.08%)
    1 / 110 (0.91%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    1
    3
    1
    0
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 110 (0.91%)
    1 / 13 (7.69%)
    2 / 110 (1.82%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    0
    Anaemia
         subjects affected / exposed
    0 / 25 (0.00%)
    6 / 110 (5.45%)
    1 / 13 (7.69%)
    5 / 110 (4.55%)
    1 / 26 (3.85%)
    1 / 11 (9.09%)
         occurrences all number
    0
    6
    1
    5
    1
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 25 (8.00%)
    12 / 110 (10.91%)
    3 / 13 (23.08%)
    16 / 110 (14.55%)
    1 / 26 (3.85%)
    2 / 11 (18.18%)
         occurrences all number
    2
    12
    3
    16
    1
    2
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 110 (0.00%)
    0 / 13 (0.00%)
    0 / 110 (0.00%)
    2 / 26 (7.69%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    Diarrhoea
         subjects affected / exposed
    0 / 25 (0.00%)
    3 / 110 (2.73%)
    1 / 13 (7.69%)
    2 / 110 (1.82%)
    0 / 26 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    3
    1
    2
    0
    1
    Nausea
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    2 / 13 (15.38%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Toothache
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    0 / 13 (0.00%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    1 / 25 (4.00%)
    12 / 110 (10.91%)
    0 / 13 (0.00%)
    32 / 110 (29.09%)
    2 / 26 (7.69%)
    1 / 11 (9.09%)
         occurrences all number
    1
    12
    0
    32
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 25 (0.00%)
    4 / 110 (3.64%)
    1 / 13 (7.69%)
    6 / 110 (5.45%)
    1 / 26 (3.85%)
    0 / 11 (0.00%)
         occurrences all number
    0
    4
    1
    6
    1
    0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    0 / 13 (0.00%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Furuncle
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    1 / 13 (7.69%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 25 (0.00%)
    0 / 110 (0.00%)
    0 / 13 (0.00%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Malaria
         subjects affected / exposed
    6 / 25 (24.00%)
    15 / 110 (13.64%)
    3 / 13 (23.08%)
    13 / 110 (11.82%)
    5 / 26 (19.23%)
    6 / 11 (54.55%)
         occurrences all number
    6
    15
    3
    13
    6
    7
    Schistosomiasis
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 110 (0.91%)
    1 / 13 (7.69%)
    0 / 110 (0.00%)
    0 / 26 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 25 (4.00%)
    16 / 110 (14.55%)
    0 / 13 (0.00%)
    27 / 110 (24.55%)
    1 / 26 (3.85%)
    0 / 11 (0.00%)
         occurrences all number
    1
    19
    0
    29
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jul 2021
    Changes have been implemented due to the availability of data from another ongoing study (CKAF156A2202). The changes are related to safety and efficacy data of KAF156 combined with LUM-SDF in pediatric patients (2 to <12 years of age).

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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