Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as KAE609 (Cipargamin), Cipargamin
KAE609 · 9 trials · 4 indications
ACPR is defined as the absence of parasitemia on Study Day 29 irrespective of axillary temperature, without previously meeting any of the criteria of Early Treatment Failure (ETF) or Late Clinical Failure (LCF) or Late Parasitological Failure (LPF).
A blood draw was performed at each collection time point for parasitemia assessment.
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.
To observe the exposure-response (PK/PD) relationship for a single dose of KAE609. The key parameter is MIC, defined as the concentration at which the relative rate of change in parasitemia is equal to zero. Approximation of MIC will assist in identifying the optimal dose of KAE609, which will be one component of a future combination antimalarial. MIC could not be determined due to small sample size no data was collected from any participants.
28-day cure rate was measured by the endpoint of complete cure without recrudescence before Day 29. The primary variable of 28-day cure rate was defined as the proportion of patients with clearance of asexual parasitemia (by blood film) by day 6 of the study, and without subsequent recrudescence (by blood film).
Calculated based on parasite count in blood. In thin film, use actual WBCs/µl, of blood to calculate parasite density by using the following formula: parasites/µl= #parasites× actual WBC/#WBCs counted. In thick film, assume that there are 250 RBCs per HPF, RBC count from 8 HPF equal 2000 RBC, Use actual RBCs/µl blood to calculate parasite density by using the following formula: parasites/µl= # of parasites in 8HPF/2000)× actual RBC.
The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.
| Arm | Type | Description |
|---|---|---|
| Cohort C2: KLU156 + KAE609 | EXPERIMENTAL | KLU156 + KAE609 was administered orally with light meal. |
| Cohort C2: SoC (Artemether + lumefantrine) | ACTIVE_COMPARATOR | Artemether + lumefantrine was administered orally as per label. |
| Cohort B1: Cipargamin + INE963 | EXPERIMENTAL | Cohort B1: Cipargamin + INE963 |
| Cohort B1: SoC (Artemether 80 mg + lumefantrine 480 mg) | ACTIVE_COMPARATOR | Cohort B1: SoC (Artemether 80 mg + lumefantrine 480 mg) |
| Cohort B2: KLU156 400/480 mg + KAE609 75 mg | EXPERIMENTAL | KLU156 \[(400 mg KAF156, 480 mg Lumefantrine (LUM)-solid dispersion formulation (SDF)\] + KAE609 75 mg was administered orally with light meal as a single dose. |
| Cohort B2: SoC (Artemether 80 mg + lumefantrine 480 mg) | ACTIVE_COMPARATOR | Artemether 80 mg + lumefantrine 480 mg was administered twice a day for 3 days with a standard meal or drink rich in fat within 30 min of dosing, as per label. |
| IV Cipargamin 20 mg | EXPERIMENTAL | 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). |
| IV Cipargamin 40 mg | EXPERIMENTAL | 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). |
| IV Artesunate | ACTIVE_COMPARATOR | Participants received IV artesunate according to label and followed by oral medication (Coartem® b.i.d. for 3 days). |
| Treatment arm 1: KAE609 10 mg Single Dose (SD) | EXPERIMENTAL | KAE609 10 mg once daily (QD) for 1 day |
| Treatment arm 2:KAE609 25 mg SD | EXPERIMENTAL | KAE609 25 mg once daily (QD) for 1 day |
| Treatment arm 3:KAE609 10 mg 3 Days | EXPERIMENTAL | KAE609 10 mg (QD) for 3 days |
| Treatment arm 4:KAE609 50 mg SD | EXPERIMENTAL | KAE609 50 mg once daily (QD) for 1 day |
| Treatment arm 5:KAE609 25 mg 3 Days | EXPERIMENTAL | KAE609 25 mg once daily (QD) for 3 days |
| Treatment arm 6:KAE609 75 mg SD | EXPERIMENTAL | KAE609 75 mg once daily (QD) for 1 day |
| Treatment arm 7:KAE609 50 mg 3 Days | EXPERIMENTAL | KAE609 50 mg once daily (QD) for 3 days |
| Treatment arm 8: KAE609 150 mg SD | EXPERIMENTAL | KAE609 150 mg once daily (QD) for 1 day |
| Treatment arm 9: Coartem Control | ACTIVE_COMPARATOR | Coartem® control |
| Dose 1: 30 mg | EXPERIMENTAL | Single dose of KAE609 30 mg |
| Dose 2: 20 mg | EXPERIMENTAL | Single dose of KAE609 20 mg |
| Dose 3: 10 mg | EXPERIMENTAL | Single dose of KAE609 10 mg |
| Dose 4: 15 mg | EXPERIMENTAL | Single dose of KAE609 15 mg |
| Cohort 1 | EXPERIMENTAL | 6-12 subjects with Plasmodium falciparum malaria will receive 75 mg KAE609 as a single dose |
| Cohort 2 | EXPERIMENTAL | 6-12 subjects with Plasmodium falciparum malaria will receive 150 mg KAE609 as a single dose |
| Cohort 3 | EXPERIMENTAL | 6 to 12 subjects with Plasmodium falciparum malaria will receive 225 mg KAE609 as a single dose |
| Cohort4 | EXPERIMENTAL | 6- 12 subjects with Plasmodium falciparum malaria will receive 300 mg KAE609 as a single dose |
| Cohort A1: 10.5 mg/placebo | EXPERIMENTAL | Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel. |
| Cohort A2: 30 mg/placebo | EXPERIMENTAL | Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel. |
| Cohort A3: 75 mg/placebo | EXPERIMENTAL | Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel. |
| Cohort A4: 120 mg/placebo | EXPERIMENTAL | Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel. |
| Cohort A5: 210 mg/placebo | EXPERIMENTAL | Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel. |
| Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days | EXPERIMENTAL | Multiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel. |
| Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days | EXPERIMENTAL | Multiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel. |
| Name | Type | Description |
|---|---|---|
| KAE609 | DRUG | oral capsules administered in combination with KLU156 |
| SoC (Coartem) | DRUG | Standard of Care |
| KLU156 | DRUG | oral sachet formulation (KAF156+LUM-SDF) administered in combination with cipargamin (KAE609) |
| KAE609 (Cipargamin) | DRUG | oral KAE609 (Cipargamin) |
| INE963 | DRUG | oral INE963 |
| Cipargamin | DRUG | Cipargamin, 20 mg or 40 mg, by intravenous administration of solution for injection |
| IV Artesunate | DRUG | Artesunate, 2.4 mg/kg or 3 mg/kg, by intravenous administration of reconstituted solution |
| Coartem | DRUG | Oral standard of care (Coartem tablets, dosed per weight, as per label) |
| Placebo | DRUG | matching placeo for iv administration |
Inclusion Criteria: 1. Male and female participants 2 to \<12 years of age at screening. 2. Participants must have acute uncomplicated P. falciparum malaria mono infection at screening confirmed by a parasite count between 1,000 to 150,000 asexual parasite count/μl of blood for P. falciparum. 3. Pa...
KAE609 is an investigational small molecule being developed for the treatment of uncomplicated Plasmodium falciparum malaria. It is also being studied for malaria cure rate. It is not yet approved for any indication and remains in clinical development.
KAE609 is being developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor of the clinical program evaluating KAE609 in malaria.
KAE609 is in Phase 2 clinical development. It has completed Phase 1 and Phase 2 trials and has one active Phase 2 trial currently recruiting. It is investigational and has not been approved by the FDA.
KAE609 has been studied in four trials. The active Phase 2 trial is NCT07811908 (Cohort C2) in uncomplicated Plasmodium falciparum malaria. Completed trials include Phase 2 studies NCT07811882 (Cohort B1) and NCT07235033 (Cohort B2), plus Phase 1 study NCT04321252 in healthy subjects.
Yes, KAE609 is also known as cipargamin. Both names refer to the same investigational antimalarial small molecule developed by Novartis AG.
The Phase 2 KAE609 trials are being conducted in multiple African countries, including Burkina Faso, Côte d’Ivoire, Gabon, Ghana, Kenya, Rwanda, and Uganda. The completed Phase 1 trial NCT04321252 was conducted in Belgium.