Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44393   clinical trials with a EudraCT protocol, of which   7405   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An adaptive, randomized, active-controlled, open-label, sequential cohort, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of intravenous cipargamin (KAE609) in adult and pediatric participants with severe Plasmodium falciparum malaria (KARISMA – KAE609’s Role in Severe Malaria)

    Summary
    EudraCT number
    		 2020-005035-70
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    20 Aug 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Mar 2026
    First version publication date
    07 Mar 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CKAE609B12201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04675931
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Aug 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Aug 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to assess the efficacy of intravenous (IV) cipargamin. Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.
    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 2022
    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: 46
    Country: Number of subjects enrolled
    Congo, The Democratic Republic of the: 19
    Country: Number of subjects enrolled
    Côte d’Ivoire: 106
    Country: Number of subjects enrolled
    Kenya: 22
    Country: Number of subjects enrolled
    Mozambique: 1
    Country: Number of subjects enrolled
    Rwanda: 47
    Country: Number of subjects enrolled
    Uganda: 13
    Worldwide total number of subjects
    254
    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)
    40
    Children (2-11 years)
    154
    Adolescents (12-17 years)
    24
    Adults (18-64 years)
    36
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 316 participants were screened for the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Treatment allocation, dose information, PK/AAG assessment schedule and concentration data, as well as other data that could result in systematic unblinding, were not available to the Clinical Trial Team (CTT) (particularly clinicians, trial statisticians, trial programmers) until the database was locked after IA of Cohorts 1-2. After interim database lock, the CTT was unblinded with the results, however, the blinding was continued for Cohorts 3-5 until the final database was locked.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IV Cipargamin 20 mg
    Arm description
    		 Participants received intravenous cipargamin 20 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cipargamin
    Investigational medicinal product code
    Other name
    KAE609
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received intravenous cipargamin 20 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).

    Arm title
    		 IV Cipargamin 40 mg
    Arm description
    		 Participants received intravenous cipargamin 40 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cipargamin
    Investigational medicinal product code
    Other name
    KAE609
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received intravenous cipargamin 40 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).

    Arm title
    		 IV Artesunate
    Arm description
    		 Participants received IV artesunate according to label and followed by oral medication (Coartem® b.i.d. for 3 days).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Artesunate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV artesunate according to label and followed by oral medication (Coartem® b.i.d. for 3 days).

    Number of subjects in period 1 [1]
    		IV Cipargamin 20 mg IV Cipargamin 40 mg IV Artesunate
    Started
    20
    114
    117
    Completed
    20
    114
    116
    Not completed
    0
    0
    1
         Lost to follow-up
    -
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Two patients randomized to IV Cipargamin 40 mg and one patient randomized to IV Artesunate discontinued the study before receiving any dose of study treatment.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    IV Cipargamin 20 mg
    Reporting group description
    		 Participants received intravenous cipargamin 20 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).

    Reporting group title
    IV Cipargamin 40 mg
    Reporting group description
    		 Participants received intravenous cipargamin 40 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).

    Reporting group title
    IV Artesunate
    Reporting group description
    		 Participants received IV artesunate according to label and followed by oral medication (Coartem® b.i.d. for 3 days).

    Reporting group values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg IV Artesunate Total
    Number of subjects
    		 20 114 117 251
    Age Categorical
    Units: participants
        6 months to < 2 years
    		 0 21 18 39
        2 to <6 years
    		 0 37 39 76
        6 to <12 years
    		 0 38 40 78
        12 to <18 years
    		 9 7 7 23
        18 to <65 years
    		 11 11 13 35
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 22.7 ( 10.07 ) 7.7 ( 7.81 ) 8.6 ( 9.13 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 9 49 64 122
        Male
    		 11 65 53 129
    Race
    Units: Subjects
        Black or African American
    		 20 114 117 251

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    IV Cipargamin 20 mg
    Reporting group description
    		 Participants received intravenous cipargamin 20 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).

    Reporting group title
    IV Cipargamin 40 mg
    Reporting group description
    		 Participants received intravenous cipargamin 40 mg, as a minimum of two doses every 24 hours, not exceeding 3 doses followed by oral medication (Coartem®, twice daily [b.i.d.] for 3 days).

    Reporting group title
    IV Artesunate
    Reporting group description
    		 Participants received IV artesunate according to label and followed by oral medication (Coartem® b.i.d. for 3 days).

    Primary: Percentage of Participants Achieving at Least 90% Reduction in Plasmodium falciparum (P. falciparum) at 12 Hours

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving at Least 90% Reduction in Plasmodium falciparum (P. falciparum) at 12 Hours [1] [2]
    End point description
    A blood draw was performed at each collection time point for parasitemia assessment.
    End point type
    Primary
    End point timeframe
    12 Hours
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were planned for this endpoint.
    [2] - 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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    117
    Units: percentage of participants
        number (not applicable)
    93.0
    39.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving Clinical Success at 48 Hours

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving Clinical Success at 48 Hours [3]
    End point description
    Clinical success was a composite endpoint based on following criteria: 1. Was participant dead or alive 2. Presence of asexual parasites (yes/no) 3. Presence of any of the key signs of severe malaria (yes/no)
    End point type
    Secondary
    End point timeframe
    48 Hours
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    117
    Units: percentage of participants
        number (confidence interval 90%)
    85.1 (78.5 to 90.3)
    74.4 (66.9 to 80.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Individual Signs of Severe Malaria Over Time

    		 Close Top of page
    End point title
    		 Percentage of Participants With Individual Signs of Severe Malaria Over Time [4]
    End point description
    Individual signs of severe malaria over time were monitored for the presence of the following signs of severe malaria during the entire study duration: 1. Altered consciousness - Prostration or GCS < 11 for participants > 5 years / BCS < 3 for participants =< 5 years of age 2. Renal Impairment - Serum creatinine > 3xULN or > 3 mg/dL or need for renal replacement therapy 3. Acidosis - Serum lactate > 4 mmol/L 4. Respiratory distress - present or absent 5. Severe anemia - Hb < 5 g/dl or Hb < 7g/dl in pediatric and adults respectively or need of blood transfusion 6. Jaundice - Serum bilirubin > 3 g/dl 7. Hypoglycemia- plasma glucose < 40 mg/dL
    End point type
    Secondary
    End point timeframe
    Baseline to Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    117
    Units: percentage of participants
    number (not applicable)
        Baseline, at Least One Sign
    98.2
    100.0
        Baseline, at Least Two Signs
    43.9
    45.3
        Baseline, at Least Three Signs
    14.0
    17.9
        Baseline, at Least Four Signs
    3.5
    10.3
        Baseline, at Least Five Signs
    0.9
    4.3
        Baseline, at Least Six Signs
    0
    0.9
        Day 29, at Least One Sign
    6.2
    7.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants Developing Hemolysis (Early and Delayed) After Treatment

    		 Close Top of page
    End point title
    		 Percentage of Participants Developing Hemolysis (Early and Delayed) After Treatment [5]
    End point description
    Development (early and delayed) of hemolysis after treatments was defined as follows: Early Hemolytic anemia was defined as 10% or greater decrease in hemoglobin levels and an increase of lactate dehydrogenase (LDH) levels to >390 U/L, or an increase of >= 10% above baseline occurring up to Day 8 of the study. Delayed hemolytic anemia occurred > 7 days after initiation of parenteral study drug (IV artesunate or IV cipargamin) during the study period. The event was characterized by a 10% or greater decrease in hemoglobin levels accompanied by increase of LDH levels to >390 U/L, or an increase of >= 10% compared to the values measured at Day 8 of the study.
    End point type
    Secondary
    End point timeframe
    Day 8 and Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    117
    Units: percentage of participants
    number (not applicable)
        Early Hemolysis
    54.4
    62.1
        Delayed Hemolysis
    3.5
    3.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Neurological Sequelae at Day 29

    		 Close Top of page
    End point title
    		 Percentage of Participants With Neurological Sequelae at Day 29 [6]
    End point description
    Detailed neurological examination was conducted and relevant medical history collected to assess the extent of neurological signs and symptoms at baseline and to monitor the extent of neurological sequelae in follow-up visits.
    End point type
    Secondary
    End point timeframe
    Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    113
    115
    Units: percentage of participants
    number (not applicable)
        Speech Impairment
    0
    0.9
        Hemiplegia or Hemiparesis
    0
    0.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving at Least 90% Reduction in Plasmodium falciparum (P. falciparum)

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving at Least 90% Reduction in Plasmodium falciparum (P. falciparum) [7]
    End point description
    A blood draw was performed at each collection time point for parasitemia assessment.
    End point type
    Secondary
    End point timeframe
    24 hours and 48 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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    117
    Units: percentage of participants
    number (confidence interval 95%)
        24 Hours Post-Dose
    100.0 (96.8 to 100.0)
    97.4 (92.7 to 99.5)
        48 Hours Post-Dose
    100.0 (96.8 to 100.0)
    99.1 (95.3 to 100.0)
    No statistical analyses for this end point

    Secondary: Time to Parasite Clearance (PCT)

    		 Close Top of page
    End point title
    		 Time to Parasite Clearance (PCT) [8]
    End point description
    Parasite clearance time (PCT) was defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 24 hours.
    End point type
    Secondary
    End point timeframe
    Up to 72 hours
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    113
    116
    Units: hours
        median (confidence interval 95%)
    18.0 (12.2 to 18.2)
    36.0 (30.0 to 36.1)
    No statistical analyses for this end point

    Secondary: Parasite Clearance Estimator (PCE) Slope Half-life

    		 Close Top of page
    End point title
    		 Parasite Clearance Estimator (PCE) Slope Half-life [9]
    End point description
    Slope half-life (hours) for parasite clearance was calculated for each patient using the WWARN (World Wide Antimalarial Resistance Network) Parasite Clearance Estimator.
    End point type
    Secondary
    End point timeframe
    Up to 72 hours
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    108
    114
    Units: hours
        median (full range (min-max))
    1.10 (0.27 to 10.03)
    2.21 (0.65 to 10.75)
    No statistical analyses for this end point

    Secondary: Time to Fever Clearance (FCT)

    		 Close Top of page
    End point title
    		 Time to Fever Clearance (FCT) [10]
    End point description
    Fever clearance time (FCT) was defined as the time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours.
    End point type
    Secondary
    End point timeframe
    Up to 72 hours
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    28
    39
    Units: hours
        median (confidence interval 95%)
    6.1 (0.6 to 11.7)
    17.8 (6.1 to 18.0)
    No statistical analyses for this end point

    Secondary: P. falciparum Parasite Reduction Ratios (PRR) at 12, 24 and 48 Hours

    		 Close Top of page
    End point title
    		 P. falciparum Parasite Reduction Ratios (PRR) at 12, 24 and 48 Hours [11]
    End point description
    PRR was defined as the ratio of asexual parasite at baseline divided by asexual parasite at post-baseline. If the asexual parasite count at post-baseline was 0, the half value of detection limit was used to calculate the ratio.
    End point type
    Secondary
    End point timeframe
    12 hours, 24 hours, and 48 hours
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    116
    Units: ratio
    median (full range (min-max))
        12 Hours n=114,116
    1347.8 (2.4 to 48092.3)
    7.5 (1.0 to 9582.8)
        24 Hours n=114,116
    4092.5 (25.1 to 48092.3)
    560.6 (4.7 to 25525.9)
        48 Hours n=113,116
    7175.1 (292.0 to 51495.5)
    5509.1 (58.1 to 72470.1)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Recrudescence and Reinfection

    		 Close Top of page
    End point title
    		 Percentage of Participants With Recrudescence and Reinfection [12]
    End point description
    Recrudescence was defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline. Reinfection was defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline. Reinfection and Recrudescence were confirmed by polymerase chain reaction (PCR) analysis.
    End point type
    Secondary
    End point timeframe
    Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    112
    114
    Units: percentage of participants
    number (not applicable)
        Recrudescence
    2.7
    1.8
        Reinfection
    8.0
    7.9
    No statistical analyses for this end point

    Secondary: Time to Switch to Oral Therapy

    		 Close Top of page
    End point title
    		 Time to Switch to Oral Therapy [13]
    End point description
    Time to switch participants from IV therapy to Coartem (standard of drug for oral therapy) was analyzed.
    End point type
    Secondary
    End point timeframe
    Day 3 to Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    117
    Units: hours
        median (confidence interval 95%)
    43.3 (42.3 to 44.2)
    44.4 (43.6 to 44.9)
    No statistical analyses for this end point

    Secondary: Time to Discharge From Hospital

    		 Close Top of page
    End point title
    		 Time to Discharge From Hospital [14]
    End point description
    End point type
    Secondary
    End point timeframe
    Day 3 to Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    114
    116
    Units: hours
        median (confidence interval 95%)
    73.1 (72.9 to 73.2)
    73.1 (72.9 to 73.1)
    No statistical analyses for this end point

    Secondary: Time to Recover From Prostration

    		 Close Top of page
    End point title
    		 Time to Recover From Prostration [15]
    End point description
    To assess recovery of participants as measured by time to recovery from prostration compared to baseline.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 29
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    109
    116
    Units: hours
        median (confidence interval 95%)
    12.4 (12.1 to 18.2)
    18.3 (17.8 to 23.7)
    No statistical analyses for this end point

    Secondary: Number of Participants With Adverse Events or Serious Adverse Events, or Who Died

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events or Serious Adverse Events, or Who Died
    End point description
    Adverse events (AEs) and serious adverse events (SAEs) were collected from first dosing. Death routine laboratory assessments were assessed up to last follow-up visit or until the event had resolved to baseline grade or better, or the event was assessed stable by the investigator, or the participant was lost to follow-up or withdrew consent.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 29
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg IV Artesunate
    Number of subjects analysed
    20
    114
    117
    Units: participants
        AEs
    12
    79
    73
        SAEs
    0
    5
    4
        Deaths
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Observed Maximum Plasma Concentration (Cmax) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Observed Maximum Plasma Concentration (Cmax) of IV Cipargamin [16]
    End point description
    Blood samples were collected for pharmacokinetics characterization. Cmax is the maximum (peak) observed plasma concentration of cipargamin after dose administration. Cmax was listed and summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    20
    55
    Units: ng/mL
    geometric mean (confidence interval 90%)
        Dose 1 n=18,55
    1350 (1150 to 1570)
    3230 (2870 to 3630)
        Dose 2 n-20,55
    1390 (1150 to 1690)
    3420 (3020 to 3880)
        Dose 3 n=3,1
    1160 (553 to 2430)
    2720 (999 to 9999)
    No statistical analyses for this end point

    Secondary: Time of Maximum Observed Drug Concentration Occurrence (Tmax) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Time of Maximum Observed Drug Concentration Occurrence (Tmax) of IV Cipargamin [17]
    End point description
    Blood samples were collected for pharmacokinetics characterization. Tmax was listed and summarized using descriptive statistics. Time to reach maximum observed plasma concentration of cipargamin after dose administration.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    20
    55
    Units: hours
    geometric mean (confidence interval 90%)
        Dose 1 n=18,55
    0.099 (0.073 to 0.135)
    0.106 (0.089 to 0.125)
        Dose 2 n=20,55
    0.221 (0.133 to 0.366)
    0.158 (0.116 to 0.216)
        Dose 3 n=3,1
    0.141 (0.007 to 2.79)
    0.05 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of IV Cipargamin [18]
    End point description
    Blood samples were collected for pharmacokinetics characterization. AUClast was listed and summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    19
    55
    Units: h*ng/mL
    geometric mean (confidence interval 90%)
        Dose 1 n=18,55
    8150 (6930 to 9580)
    18800 (16900 to 21000)
        Dose 2 n=19,55
    19100 (16100 to 22800)
    38700 (34700 to 43100)
        Dose 3 n=3,1
    18600 (6330 to 54400)
    40400 (999 to 99999)
    No statistical analyses for this end point

    Secondary: Area Under the Concentration Time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Area Under the Concentration Time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of IV Cipargamin [19]
    End point description
    Blood samples were collected for pharmacokinetics characterization. AUC(0-inf) post last dose was listed and summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    15
    53
    Units: h*ng/mL
    geometric mean (confidence interval 90%)
        Dose 1 n=0,0
    999 (999 to 999)
    999 (999 to 999)
        Dose 2 n=15,53
    21300 (18000 to 25200)
    40000 (36000 to 44500)
        Dose 3 n=3,1
    18800 (6360 to 55500)
    40400 (999 to 99999)
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-time Curve From the Time 0 to 24 hours (AUC0-24hours) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Area Under the Plasma Concentration-time Curve From the Time 0 to 24 hours (AUC0-24hours) of IV Cipargamin [20]
    End point description
    Blood samples were collected for pharmacokinetics characterization. AUC(0-24h) was listed and summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    19
    55
    Units: h*ng/mL
    geometric mean (confidence interval 90%)
        Dose 1 n=18,55
    8170 (6950 to 9590)
    19200 (17300 to 21300)
        Dose 2 n=19,54
    11900 (10700 to 13200)
    28500 (25900 to 31400)
        Dose 3 n=3,1
    10100 (5800 to 17600)
    26500 (999 to 99999)
    No statistical analyses for this end point

    Secondary: Terminal Elimination Half Life (T1/2) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Terminal Elimination Half Life (T1/2) of IV Cipargamin [21]
    End point description
    Blood samples were collected for pharmacokinetics characterization. The half-life post last dose was summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    Notes
    [21] - 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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    15
    53
    Units: hours
    geometric mean (confidence interval 90%)
        Dose 1 n=0,0
    999 (999 to 999)
    999 (999 to 999)
        Dose 2 n=15,53
    18 (15.7 to 20.7)
    11.6 (10.6 to 12.6)
        Dose 3 n=3,1
    16.2 (8.35 to 31.4)
    10.8 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Total Systemic Clearance for Intravenous Administration (CL) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Total Systemic Clearance for Intravenous Administration (CL) of IV Cipargamin [22]
    End point description
    Blood samples were collected for pharmacokinetics characterization. CL post last dose was summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    Notes
    [22] - 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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    15
    53
    Units: L/h
    geometric mean (confidence interval 90%)
        Dose 1 n=0,0
    999 (999 to 999)
    999 (999 to 999)
        Dose 2 n=15,53
    0.939 (0.793 to 1.11)
    0.66 (0.576 to 0.755)
        Dose 3 n=3,1
    1.06 (0.36 to 3.15)
    0.99 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of IV Cipargamin

    		 Close Top of page
    End point title
    		 Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of IV Cipargamin [23]
    End point description
    Blood samples were collected for pharmacokinetics characterization. Vz post last dose was listed and summarized using descriptive statistics.
    End point type
    Secondary
    End point timeframe
    Day 1 - Day 8
    Notes
    [23] - 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: Data are reported for applicable reporting groups.
    End point values
    		 IV Cipargamin 20 mg IV Cipargamin 40 mg
    Number of subjects analysed
    15
    53
    Units: liters
    geometric mean (confidence interval 90%)
        Dose 1 n=0,0
    999 (999 to 999)
    999 (999 to 999)
        Dose 2 n=15,53
    24.5 (21.2 to 28.2)
    11 (9.34 to 13)
        Dose 3 n=3,1
    24.9 (15 to 41.1)
    15.5 (-999 to 999)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus 29 days post treatment, up to a maximum duration of 36 days.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    IV Cipargamin 20mg
    Reporting group description
    		 IV Cipargamin 20mg

    Reporting group title
    IV Artesunate
    Reporting group description
    		 IV Artesunate

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    IV Cipargamin 40mg
    Reporting group description
    		 IV Cipargamin 40mg

    Serious adverse events
    		 IV Cipargamin 20mg IV Artesunate Total IV Cipargamin 40mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 117 (3.42%)
    9 / 251 (3.59%)
    5 / 114 (4.39%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 117 (0.85%)
    1 / 251 (0.40%)
    0 / 114 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Quadriparesis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 117 (0.85%)
    1 / 251 (0.40%)
    0 / 114 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 117 (0.00%)
    1 / 251 (0.40%)
    1 / 114 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 117 (1.71%)
    3 / 251 (1.20%)
    1 / 114 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 117 (0.85%)
    1 / 251 (0.40%)
    0 / 114 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 117 (0.00%)
    1 / 251 (0.40%)
    1 / 114 (0.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Malaria
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 117 (0.00%)
    2 / 251 (0.80%)
    2 / 114 (1.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 IV Cipargamin 20mg IV Artesunate Total IV Cipargamin 40mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 20 (35.00%)
    50 / 117 (42.74%)
    114 / 251 (45.42%)
    57 / 114 (50.00%)
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 20 (25.00%)
    35 / 117 (29.91%)
    80 / 251 (31.87%)
    40 / 114 (35.09%)
         occurrences all number
    5
    36
    81
    40
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 117 (1.71%)
    5 / 251 (1.99%)
    1 / 114 (0.88%)
         occurrences all number
    2
    2
    5
    1
    Infections and infestations
    Malaria
         subjects affected / exposed
    0 / 20 (0.00%)
    12 / 117 (10.26%)
    28 / 251 (11.16%)
    16 / 114 (14.04%)
         occurrences all number
    0
    12
    28
    16
    Rhinitis
         subjects affected / exposed
    1 / 20 (5.00%)
    4 / 117 (3.42%)
    12 / 251 (4.78%)
    7 / 114 (6.14%)
         occurrences all number
    1
    4
    12
    7
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 20 (0.00%)
    5 / 117 (4.27%)
    12 / 251 (4.78%)
    7 / 114 (6.14%)
         occurrences all number
    0
    5
    12
    7

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Sat Mar 28 06:32:15 CET 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA