Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as KAE609 (Cipargamin)
KAE609 · 6 trials · 3 indications
ACPR is defined as absence of parasitaemia (PS) on Study Day 29 regardless of axillary temperature, in patients who have not previously met any of the criteria of Early Treatment Failure (ETF), Late Clinical Failure (LCF), or Late Parasitological Failure (LPF). A patient was considered as PCR-corrected ACPR at Day 29 when the patient did not meet any of the criteria of ETF (up to Day 4), LCF (Day 5 to Day 29), or LPF (Day 8 to Day 29), and was absence of PS on Day 29, unless the presence of PS detected after 7 days (Day 8 or later) was due to reinfection. The presence of PS after 7 days of treatment initiation was considered as a reinfection only when the PS had cleared before Day 8, and none of the parasite strain(s) detected on or after Day 8 matched with the parasite strain at baseline.
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 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. |
| 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) |
| Coartem | DRUG | Control Arm |
| Placebo | DRUG | matching placeo for iv administration |
Inclusion Criteria: 1. Male and female patients ≥12 years of age at screening. 2. Patients 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. Patients must we...
KAE609 is an investigational small molecule being developed for malaria, including uncomplicated Plasmodium falciparum malaria. It is being studied for its ability to achieve cure rates in patients with this infection. The drug is currently in clinical development and is not approved for use.
KAE609 is being developed by Novartis AG, a multinational pharmaceutical company listed on the New York Stock Exchange under the ticker NVS. Novartis is conducting clinical trials to evaluate the safety and efficacy of KAE609 in patients with malaria.
KAE609 is in Phase 2 clinical development. It has completed four clinical trials, including Phase 1 and Phase 2 studies, with a total enrollment of 297 participants. The drug remains investigational and has not received regulatory approval.
KAE609 has been studied in four completed clinical trials. These include NCT01836458, a Phase 2 study in adult male patients with P. falciparum monoinfection in Vietnam; NCT03334747, a Phase 2 safety study in adults with uncomplicated malaria across five African countries; NCT04321252, a Phase 1 study in healthy subjects in Belgium; and NCT07235033, a Phase 2 platform study in participants with uncomplicated malaria.
Yes, KAE609 is also known as Cipargamin. Both names refer to the same investigational small molecule drug being developed by Novartis for the treatment of malaria. Researchers and clinical trial registries may use either name when referring to this compound.
KAE609 has been studied in both oral and intravenous forms. Clinical trials have evaluated the drug in healthy volunteers and in patients with malaria. The completed studies include assessments of safety, tolerability, pharmacokinetics, and efficacy in achieving cure rates for uncomplicated Plasmodium falciparum malaria.