KAE609 will be evaluated primarily for hepatic safety of single and multiple doses in sequential cohorts with increasing doses.This study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
188
Novartis Investigative Site
Lambaréné, Gabon
Novartis Investigative Site
Kintampo, Ghana
Novartis Investigative Site
Navrango, Ghana
Novartis Investigative Site
Bamako, Mali
Number of Participants With at Least 2 CTCAE Grades Increase From Baseline in Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)
The occurrence of at least 2 CTCAE grades increase from baseline in ALT or AST during the 4 weeks study period was evaluated to characterize hepatic safety aspects of single and multiple ascending doses of KAE609 in adult malaria subjects for treatment of uncomplicated malaria caused by plasmodium falciparum. If 2 patients in a 10 patient cohort (Cohorts 1 and 2) or 3 patients in a 20 patient cohort (Cohorts 3, 4 and 5) had at least 2 CTCAE grades increase from Baseline in ALT or AST, recruitment was suspended and a review of liver safety (and any other relevant data) by safety review committee was initiated. Any further progression of the study was based on the decision by the safety review committee.
Time frame: Day 29
Percentage of Participants With Polymerase Chain Reaction (PCR)-Corrected and Uncorrected Adequate Clinical and Parasitological Response (ACPR) at Day 15 and Day 29
PCR-corrected and PCR-uncorrected were evaluated at Days 15 and 29 (i.e., 14 and 28 days post-dose). The presence of parasitaemia after 7 days due to reinfection was considered as PCR-corrected ACPR. Missing blood smear data at Day 15 visit and thereafter were not considered as responder for the visit unless there was a later blood smear test indicating no parasitaemia.
Time frame: Day 15, Day 29
Parasite Clearance Time (PCT)
Parasite Clearance Time (PCT) is defined as the time from the first dose until the first total and continued disappearance of asexual parasite forms which remained at least a further 48 hours. In case a patient received rescue medication before (parasite) clearance, the time to event was censored at the first use of rescue medication.
Time frame: Day 29
Fever Clearance Time (FCT)
Fever Clearance Time (FCT) is defined as the time from the first dose until the first time the axillary body temperature decreased below and remained below 37.5°C axillary or 38.0°C oral/tympanic/rectal for at least a further 24 hours. In case a patient received rescue medication before (fever) clearance, the time to event was censored at the first use of rescue medication.
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Novartis Investigative Site
Sotouba, Mali
Novartis Investigative Site
Kigali, Rwanda
Novartis Investigative Site
Bushenyi, Uganda
Novartis Investigative Site
Kampala, Uganda
Novartis Investigative Site
Tororo, Uganda
Time frame: Day 29
Time to Recrudescence and Reinfection at Study Day 29
Time to recrudescence is calculated from the date of first study medication to the date of first event. Participants without recrudescence/reinfection after Day 7 are censored at the time of treatment failure or at the time of last parasite assessment if no treatment failure occured.
Time frame: Day 29
Maximum Peak Observed Concentration (Cmax)
Maximum Peak Observed Concentration (Cmax)
Time frame: Day 1, Day 3
Tmax
Tmax
Time frame: Day 1, Day 3
AUC0-24
AUC0-24
Time frame: Day 1, Day 3
Half-life (T^1/2)
Half-life (T\^1/2)
Time frame: Upto day 15 post dose