Back to resultsTo Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria
Primary Purpose
Severe Malaria
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KAE609
IV Artesunate
Coartem
Sponsored by
About this trial
This is an interventional treatment trial for Severe Malaria focused on measuring KAE609, cipargamin, artesunate, intravenous, i.v., pediatric, dose-finding, safety, tolerability, pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
Cohort 1: Participants aged ≥ 12 years with moderately severe malaria as defined in (prostration and/or repeated vomiting) without presence of other signs of severe malaria (and with high P. falciparum parasitemia (60,000-250,000 parasites per µl)
- Subsequent Cohorts 2 to 5: Participants diagnosed with severe malaria as defined in modified version of WHO criteria and P. falciparum parasite count of ≥ 5000 per µl
- Cohort 2: Participants aged ≥ 12 years
- Cohort 3: Participants aged 6 - < 12 years
- Cohort 4: Participants aged 2 - < 6 years
- Cohort 5: Participants aged ≥ 6 months - < 2 years
Exclusion Criteria:
Exclusion criteria applying to all Cohorts 1 to 5:
- Mixed Plasmodium infections
- Treatment with quinine or artemisinin derivative or any other antimalarial drug or any antibiotic with known antimalarial activity within 12 hours of screening.
Signs/symptoms of severe malnutrition in general accordance with WHO guidelines:
- Under 18 years: <-3 Z-scores of WHO growth standard for weight-for-height/length (in children < 5 years) or BMI for age (5-18 years), or very low mid-upper arm circumference (MUAC < 115 mm in children < 12 years, < 160mm 12-18 years), or bilateral pitting edema
- Over 18 years: BMI < 16 kg/m2 or MUAC < 160mm or bilateral pitting edema
Known underlying illness, surgical or medical condition, which is not related to ongoing event of severe malaria and which might jeopardize the participant's health in case of participation in the study or which might alter the distribution, metabolism or excretion of study treatment. For example:
- neurological or neurodegenerative disorders,
- cardiac, renal, or hepatic disease, diabetes,
- epilepsy, cerebral palsy,
- known or suspected to be HIV-1 positive and/or receiving antiretroviral treatment
- malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- known or suspected cases of active infections or concurrent febrile illness such as TB, Typhoid, COVID-19 etc.
Additional exclusion criteria are as follows:
Exclusion criteria for Cohort 1:
- ALT > 5 x the upper limit of normal range (ULN), regardless the level of total bilirubin
- Total bilirubin is > 3 mg/dL
- Body weight of < 35 kg or >75 kg
Exclusion criteria for Cohort 2:
- Body weight of < 35 kg or >75 kg
- Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria
Exclusion criteria for Cohorts 3 to 5:
- Body weight of < 5 kg
- Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria
Sites / Locations
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Other
Arm Label
IV KAE609 Dose regimen 1
IV KAE609 Dose regimen 2
IV KAE609 Dose regimen 3
IV Artesunate
Coartem
Arm Description
Intravenous KAE609 (cipargamin) 20 mg
Intravenous KAE609 (cipargamin) 40 mg
Intravenous KAE609 (cipargamin) Dose regimen 3 (dose will be evaluated post Interim analysis from Cohort 1 and Cohort 2.
IV Artesunate 2.4 mg/kg (for participants weighing at least 20 kg) IV Artesunate 3 mg/kg (for participants weighing less than 20 kg)
Standard of care (Coartem) will be given to all participants for 3 days as part of treatment.
Outcomes
Primary Outcome Measures
Percentage of participants achieving at least 90% reduction in Plasmodium falciparum (P. falciparum) at 12 hours
A blood draw will be performed at each collection time point for parasitemia assessment.
Secondary Outcome Measures
Percentage of participants achieving clinical success over time
Clinical success is a composite endpoint based on following criterias:
Is participant dead or alive
Presence of asexual parasites (yes/no)
Presence of any of the key signs of severe malaria (yes/no)
Percentage of participants with individual signs of severe malaria over time
Individual signs of severe malaria over time will be monitored for the presence of the following signs of severe malaria during the entire study duration:
Altered consciousness - Prostration or GCS < 11 for participants > 5 years / BCS < 3 for participants =< 5 years of age
Renal Impairment - Serum creatinine > 3xULN or > 3 mg/dL or need for renal replacement therapy
Acidosis - Serum lactate > 4 mmol/L
Respiratory distress - present or absent
Severe anemia - Hb < 5 g/dl or Hb < 7g/dl in pediatric and adults respectively or need of blood transfusion
Jaundice - Serum bilirubin > 3 g/dl
Hypoglycemia- plasma glucose < 40 mg/dL
Percentage of participants developing hemolysis (early and delayed) after treatment
Development (early and delayed) of hemolysis after treatment are defined as follows:
Early Hemolytic anemia is defined as 10% or greater decrease in hemoglobin levels and an increase of LDH levels to >390 U/L, or an increase of >= 10% above baseline occurring up to Day 8 of the study.
Delayed hemolytic anemia might occur > 7 days after initiation of parenteral study drug (IV artesunate or IV cipargamin) during the study period. The event is 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.
Percentage of participants with neurological sequelae at Day 29
Detailed neurological examination will be conducted and relevant medical history collected under the following categories to assess the extent of neurological signs and symptoms at baseline and to monitor the extent of neurological sequelae in follow-up visits:
Consciousness
Cranial Nerve Palsy
Motor system
Convulsions
Sense organs (Examination more useful at time of hospital discharge and in follow-up visits)
Percentage of participants achieving at least 90% reduction in Plasmodium falciparum (P. falciparum)
A blood draw will be performed at each collection time point for parasitemia assessment
Time to parasite clearance (PCT)
Parasite Clearance Time (PCT) is defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 24 hours
Time to fever clearance (FCT)
Fever Clearance Time (FCT) is defined as the time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours.
Percentage of participants achieving P. falciparum parasite reduction ratios (PRR) at 12, 24 and 48 hours
PRR is defined as the ratio of asexual parasite at baseline divided by asexual parasite at post-baseline. If the asexual parasite count at post-baseline is 0, the half value of detection limit will be used to calculate the ratio.
Percentage of participants with recrudescence and reinfection
Time to event (recrudescence or reinfection) will be calculated from the time of first study medication to the date of first event if a patient experiences the event and be censored at the time of last parasite assessment if a patient does not experience the event due to whatever reason.
Reinfection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline.
Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline.
Reinfection and Recrudescence must be confirmed by PCR analysis.
Time to recover from prostration
To assess recovery of participants as measured by time (days and hours) to discharge from hospital or recovery from prostration compared to baseline.
Time to switch to oral therapy
Time to switch participants from IV therapy to Coartem (standard of drug for oral therapy) will be analyzed.
Time to discharge from hospital
All participants will be hospitalized. Time (Days and Hours) to discharge from hospital will be analyzed.
Number of Participants impacted on safety and tolerability assessments
Adverse events (AE), Serious Adverse events (SAEs) will be collected from first dosing, Death including whether in-hospital death and routine laboratory assessments will be done up to last follow-up visit or until the event has 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.
Observed maximum plasma concentration (Cmax) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time of maximum observed drug concentration occurrence (Tmax) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Area under the concentration time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.
Area Under the plasma concentration-time Curve from the time 0 to the last observed quantifiable concentration (AUC(0-t)) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-t) will be listed and summarized using descriptive statistics.
AUC(0-t) divided by the dose administered (AUC(0- t)/D) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-t)/D will be listed and summarized using descriptive statistics.
Terminal elimination half life (T^1/2) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics.
Total systemic clearance for intravenous administration (CL) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
volume of distribution during the terminal phase following intravenous elimination (Vz) of IV Cipargamin
Blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
Full Information
NCT ID
NCT04675931
First Posted
December 1, 2020
Last Updated
October 23, 2023
Sponsor
Novartis Pharmaceuticals
Collaborators
Wellcome Trust, European and Developing Countries Clinical Trials Partnership (EDCTP)
1. Study Identification
Unique Protocol Identification Number
NCT04675931
Brief Title
To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 7, 2022 (Actual)
Primary Completion Date
May 20, 2025 (Anticipated)
Study Completion Date
May 20, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
Collaborators
Wellcome Trust, European and Developing Countries Clinical Trials Partnership (EDCTP)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to identify the safe and effective dose of intravenous cipargamin in participants with moderately severe and severe malaria.
The study also intends to evaluate clinical treatment success using a novel clinical endpoint for drug development in severe malaria.
Severe malaria is a medical emergency and is affecting primarily young children in Africa. Injectable artesunate is the standard of care for the treatment of severe malaria and is highly efficacious. However, the spread of artemisinin-resistance in Plasmodium falciparum in Asian countries poses a threat for future treatment of patients with this life-threatening disease. To mitigate this risk, there is a need of another drug in malaria endemic countries. Cipargamin treatment results in rapid clearance of parasites including artemisinin resistant parasites.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Malaria
Keywords
KAE609, cipargamin, artesunate, intravenous, i.v., pediatric, dose-finding, safety, tolerability, pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
This will be an adaptive, multicenter, randomized, open label, sequential cohort study in participants aged ≥ 12 years old in Cohorts 1-2 and < 12 years old to ≥ 6 months in Cohorts 3-5 with a diagnosis of moderately severe and severe P. falciparum malaria. In Cohorts 1-2, participants will get randomized to one of the three treatment arms (2 dose of intravenous cipargamin or intravenous artesunate - comparator ). After Cohort 2, interim analysis will be performed to take one best dose of intravenous cipargamin forward for Cohorts 3-5. Participants in Cohorts 3-5 with be randomized to one of two treatments arms ( intravenous cipargamin or intravenous artesunate - comparator).
Masking
Outcomes Assessor
Masking Description
Although the study is open label however in order to minimize the potential impact of treatment knowledge, treatment allocation, dose information, PK/AAG assessment schedule and concentration data, as well as other data that may result in systematic unblinding will not be available to the Clinical Trial Team (CTT) (particularly clinicians, trial statisticians, trial programmers) until the database is locked after IA of Cohorts 1-2. After interim database lock, the CTT would be unblinded with the results, however, the blinding will then be continued for Cohorts 3-5 until the final database is locked.
Allocation
Randomized
Enrollment
252 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IV KAE609 Dose regimen 1
Arm Type
Experimental
Arm Description
Intravenous KAE609 (cipargamin) 20 mg
Arm Title
IV KAE609 Dose regimen 2
Arm Type
Experimental
Arm Description
Intravenous KAE609 (cipargamin) 40 mg
Arm Title
IV KAE609 Dose regimen 3
Arm Type
Experimental
Arm Description
Intravenous KAE609 (cipargamin) Dose regimen 3 (dose will be evaluated post Interim analysis from Cohort 1 and Cohort 2.
Arm Title
IV Artesunate
Arm Type
Active Comparator
Arm Description
IV Artesunate 2.4 mg/kg (for participants weighing at least 20 kg) IV Artesunate 3 mg/kg (for participants weighing less than 20 kg)
Arm Title
Coartem
Arm Type
Other
Arm Description
Standard of care (Coartem) will be given to all participants for 3 days as part of treatment.
Intervention Type
Drug
Intervention Name(s)
KAE609
Other Intervention Name(s)
Cipargamin
Intervention Description
Two doses of Intravenous Cipargamin will be evaluated in the initial phase of the study (Cohorts 1-2).
These doses will cover a wider exposure range and facilitate the selection of an appropriate dose for later Cohorts 3-5.
Intervention Type
Drug
Intervention Name(s)
IV Artesunate
Other Intervention Name(s)
Artesunate
Intervention Description
Parenteral artesunate is the WHO recommended first line treatment for severe malaria. Hence IV artesunate is used as comparator. Also, this will be used as rescue medication for participants where IV KAE609 is not working.
Intervention Type
Drug
Intervention Name(s)
Coartem
Other Intervention Name(s)
Artemether, Lumefantrine
Intervention Description
Oral Standard of Care
Primary Outcome Measure Information:
Title
Percentage of participants achieving at least 90% reduction in Plasmodium falciparum (P. falciparum) at 12 hours
Description
A blood draw will be performed at each collection time point for parasitemia assessment.
Time Frame
Day 1 (12 Hours)
Secondary Outcome Measure Information:
Title
Percentage of participants achieving clinical success over time
Description
Clinical success is a composite endpoint based on following criterias:
Is participant dead or alive
Presence of asexual parasites (yes/no)
Presence of any of the key signs of severe malaria (yes/no)
Time Frame
Day 3 (48 Hours), Day 4 to Day 29
Title
Percentage of participants with individual signs of severe malaria over time
Description
Individual signs of severe malaria over time will be monitored for the presence of the following signs of severe malaria during the entire study duration:
Altered consciousness - Prostration or GCS < 11 for participants > 5 years / BCS < 3 for participants =< 5 years of age
Renal Impairment - Serum creatinine > 3xULN or > 3 mg/dL or need for renal replacement therapy
Acidosis - Serum lactate > 4 mmol/L
Respiratory distress - present or absent
Severe anemia - Hb < 5 g/dl or Hb < 7g/dl in pediatric and adults respectively or need of blood transfusion
Jaundice - Serum bilirubin > 3 g/dl
Hypoglycemia- plasma glucose < 40 mg/dL
Time Frame
Day 1 to Day 29
Title
Percentage of participants developing hemolysis (early and delayed) after treatment
Description
Development (early and delayed) of hemolysis after treatment are defined as follows:
Early Hemolytic anemia is defined as 10% or greater decrease in hemoglobin levels and an increase of LDH levels to >390 U/L, or an increase of >= 10% above baseline occurring up to Day 8 of the study.
Delayed hemolytic anemia might occur > 7 days after initiation of parenteral study drug (IV artesunate or IV cipargamin) during the study period. The event is 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.
Time Frame
Day 8 and Day 29
Title
Percentage of participants with neurological sequelae at Day 29
Description
Detailed neurological examination will be conducted and relevant medical history collected under the following categories to assess the extent of neurological signs and symptoms at baseline and to monitor the extent of neurological sequelae in follow-up visits:
Consciousness
Cranial Nerve Palsy
Motor system
Convulsions
Sense organs (Examination more useful at time of hospital discharge and in follow-up visits)
Time Frame
Day 29
Title
Percentage of participants achieving at least 90% reduction in Plasmodium falciparum (P. falciparum)
Description
A blood draw will be performed at each collection time point for parasitemia assessment
Time Frame
Day 2 (24 hours), Day 3 (48 hours)
Title
Time to parasite clearance (PCT)
Description
Parasite Clearance Time (PCT) is defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 24 hours
Time Frame
Day 1 (12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Title
Time to fever clearance (FCT)
Description
Fever Clearance Time (FCT) is defined as the time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours.
Time Frame
Day 1 (12 hours), Day 2 (24 hours), Day 3 (48 hours) and Day 4 (72 hours)
Title
Percentage of participants achieving P. falciparum parasite reduction ratios (PRR) at 12, 24 and 48 hours
Description
PRR is defined as the ratio of asexual parasite at baseline divided by asexual parasite at post-baseline. If the asexual parasite count at post-baseline is 0, the half value of detection limit will be used to calculate the ratio.
Time Frame
Day 1 (12 hours), Day 2 (24 hours) and Day 3 (48 hours)
Title
Percentage of participants with recrudescence and reinfection
Description
Time to event (recrudescence or reinfection) will be calculated from the time of first study medication to the date of first event if a patient experiences the event and be censored at the time of last parasite assessment if a patient does not experience the event due to whatever reason.
Reinfection is defined as appearance of asexual parasites after clearance of initial infection with a genotype different from those parasites present at baseline.
Recrudescence is defined as appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at baseline.
Reinfection and Recrudescence must be confirmed by PCR analysis.
Time Frame
Day 29
Title
Time to recover from prostration
Description
To assess recovery of participants as measured by time (days and hours) to discharge from hospital or recovery from prostration compared to baseline.
Time Frame
Day 1 to Day 29
Title
Time to switch to oral therapy
Description
Time to switch participants from IV therapy to Coartem (standard of drug for oral therapy) will be analyzed.
Time Frame
Day 3 to Day 29
Title
Time to discharge from hospital
Description
All participants will be hospitalized. Time (Days and Hours) to discharge from hospital will be analyzed.
Time Frame
Day 3 to Day 29
Title
Number of Participants impacted on safety and tolerability assessments
Description
Adverse events (AE), Serious Adverse events (SAEs) will be collected from first dosing, Death including whether in-hospital death and routine laboratory assessments will be done up to last follow-up visit or until the event has 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.
Time Frame
Day 1 to Day 29
Title
Observed maximum plasma concentration (Cmax) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
Time of maximum observed drug concentration occurrence (Tmax) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
Area under the concentration time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
Area Under the plasma concentration-time Curve from the time 0 to the last observed quantifiable concentration (AUC(0-t)) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-t) will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
AUC(0-t) divided by the dose administered (AUC(0- t)/D) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-t)/D will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
Terminal elimination half life (T^1/2) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
Total systemic clearance for intravenous administration (CL) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
Title
volume of distribution during the terminal phase following intravenous elimination (Vz) of IV Cipargamin
Description
Blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
Time Frame
Day 1 - Day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Cohort 1: Participants aged ≥ 12 years with moderately severe malaria as defined in (prostration and/or repeated vomiting) without presence of other signs of severe malaria (and with high P. falciparum parasitemia (60,000-250,000 parasites per µl)
Subsequent Cohorts 2 to 5: Participants diagnosed with severe malaria as defined in modified version of WHO criteria and P. falciparum parasite count of ≥ 5000 per µl
Cohort 2: Participants aged ≥ 12 years
Cohort 3: Participants aged 6 - < 12 years
Cohort 4: Participants aged 2 - < 6 years
Cohort 5: Participants aged ≥ 6 months - < 2 years
Exclusion Criteria:
Exclusion criteria applying to all Cohorts 1 to 5:
Mixed Plasmodium infections
Treatment with quinine or artemisinin derivative or any other antimalarial drug or any antibiotic with known antimalarial activity within 12 hours of screening.
Signs/symptoms of severe malnutrition in general accordance with WHO guidelines:
Under 18 years: <-3 Z-scores of WHO growth standard for weight-for-height/length (in children < 5 years) or BMI for age (5-18 years), or very low mid-upper arm circumference (MUAC < 115 mm in children < 12 years, < 160mm 12-18 years), or bilateral pitting edema
Over 18 years: BMI < 16 kg/m2 or MUAC < 160mm or bilateral pitting edema
Known underlying illness, surgical or medical condition, which is not related to ongoing event of severe malaria and which might jeopardize the participant's health in case of participation in the study or which might alter the distribution, metabolism or excretion of study treatment. For example:
neurological or neurodegenerative disorders,
cardiac, renal, or hepatic disease, diabetes,
epilepsy, cerebral palsy,
known or suspected to be HIV-1 positive and/or receiving antiretroviral treatment
malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
known or suspected cases of active infections or concurrent febrile illness such as TB, Typhoid, COVID-19 etc.
Additional exclusion criteria are as follows:
Exclusion criteria for Cohort 1:
ALT > 5 x the upper limit of normal range (ULN), regardless the level of total bilirubin
Total bilirubin is > 3 mg/dL
Body weight of < 35 kg or >75 kg
Exclusion criteria for Cohort 2:
Body weight of < 35 kg or >75 kg
Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria
Exclusion criteria for Cohorts 3 to 5:
Body weight of < 5 kg
Participants diagnosed as moderately severe malaria due to repeated vomiting without presence of any of the symptoms of severe malaria
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Burkina Faso
ZIP/Postal Code
2208
Country
Burkina Faso
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ouagadougou
Country
Burkina Faso
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kinsasha
State/Province
Democratic Republic Of Congo
ZIP/Postal Code
BP 7948
Country
Congo, The Democratic Republic of the
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Abidjan
State/Province
Cote D Ivoire
ZIP/Postal Code
13BP972
Country
Côte D'Ivoire
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Agboville
State/Province
Cote D Ivoire
ZIP/Postal Code
BP 154
Country
Côte D'Ivoire
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Lambarene
ZIP/Postal Code
BP 242
Country
Gabon
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Raipur
State/Province
Chhattisgarh
ZIP/Postal Code
492099
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Surat
State/Province
Gujrat
ZIP/Postal Code
395002
Country
India
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ilorin
ZIP/Postal Code
240003
Country
Nigeria
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kigali
ZIP/Postal Code
BP 4560
Country
Rwanda
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of participants who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Learn more about this trial
To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria
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