Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
KAF156 · 4 trials · 3 indications
PCR-corrected ACPR, defined as the absence of parasitemia(PS), was evaluated on Day29. Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection.A participant was considered as PCR corrected ACPR at Day29 if the participant did not meet any of the criteria of early treatment failure (up to Day4), late clinical failure(Day5 to Day29) or late parasitological failure(Day8 to Day29), and had absence of PS on Day29 irrespective of axillary temperature unless the presence of PS after 7days(Day8 or later) was due to reinfection based on PCR genotyping.A presence of PS after 7days of treatment initiation was considered as a reinfection only if the PS was clear before Day8 and none of the parasite strain(s) detected on Day8 or later match with the parasite strain at baseline based on PCR genotyping.Given the age-independent symptoms of acute malaria, and to increase statistical power,the cohorts 1 and 2 were pooled.
PCR-corrected ACPR defined as the absence of parasitaemia was evaluated at Day 29 (i.e., 28 days post first dose) based on the short half-life of the study drugs. Microscopic species identification was confirmed and determined by PCR genotyping methods to establish malaria recrudescence/reinfection. A participant was considered as PCR-corrected ACPR at Day 29 if the participant did not meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure and was absence of parasitaemia on Day 29 irrespective of axillary temperature unless the presence of parasitaemia after 7 days was due to reinfection based on PCR. A presence of parasitaemia after 7 days of treatment initiation was considered as a reinfection only if the parasitaemia was clear before Day 8 and none of the parasite strain(s) detected on Day 8 or later matched with the parasite strain at baseline based on PCR.
Pharmacokinetic (PK) parameters were calculated based on KAF156 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. AUC0-24h was determined using non-compartmental methods.
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.
The number of subjects that became infected with malaria at each dose
The exposure-response relationship of KAF156 was explored in a PK/PD model to relate drug exposure to prophylactic efficacy using standard statistical methods such as CART or non-linear regression. Summary statistics were also provided for the malaria incidence rate by cohort and treatment arm
| Arm | Type | Description |
|---|---|---|
| Run-in - KAF156 and LUM-SDF QD for 2 days in fasted condition | EXPERIMENTAL | KAF156 and LUM-SDF QD (once daily) for 2 days in fasted condition |
| Run-in - KAF156 and LUM-SDF QD for 2 days in fed condition | EXPERIMENTAL | KAF156 and LUM-SDF QD (once daily) for 2 days in fed condition |
| Cohort 1/2 - KAF156 and LUM-SDF QD (once daily) in 3-day dose regimen | EXPERIMENTAL | KAF156 and LUM-SDF QD (once daily) in 3-day dose regimen. It was administered with a light meal and the full dose was adjusted based on patient´s body weight. |
| Cohort 1/2 - Coartem® BID (twice a day) for 3 days | ACTIVE_COMPARATOR | Coartem® BID twice a day for 3 days (It was administered with a light meal and doses were based on patient's body weight as per product label). |
| Part A - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day | EXPERIMENTAL | Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg |
| Part A - Cohort 2: KAF 800 mg and LUM 960 mg QD for 1 day | EXPERIMENTAL | Participants received a single oral dose of KAF156 800 mg and LUM-SDF 960 mg |
| Part A - Cohort 3: KAF 400 mg and LUM 960 mg QD for 2 days | EXPERIMENTAL | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days |
| Part A - Cohort 4: KAF 200 mg and LUM 480 mg QD for 3 days | EXPERIMENTAL | Participants received KAF156 200 mg and LUM-SDF 480 mg once daily via oral administration for 3 days |
| Part A - Cohort 5: KAF 400 mg and LUM 480 mg QD for 3 days | EXPERIMENTAL | Participants received KAF156 400 mg and LUM-SDF 480 mg once daily via oral administration for 3 days |
| Part A - Cohort 6: KAF 400 mg and LUM 960 mg QD for 3 days | EXPERIMENTAL | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days |
| Part A - Cohort 7: Coartem | ACTIVE_COMPARATOR | Participants received Coartem twice daily via oral administration for 3 days |
| PK Run-in Cohort: KAF 200 mg and LUM 960 mg QD for 1 day | EXPERIMENTAL | Participants received a single oral dose of KAF156 200 mg and LUM-SDF 960 mg |
| Part B - Cohort 1: KAF 400 mg and LUM 960 mg QD for 1 day | EXPERIMENTAL | Participants received a single oral dose of KAF156 400 mg and LUM-SDF 960 mg |
| Part B - Cohort 2: KAF 400 mg and LUM 960 mg QD for 2 days | EXPERIMENTAL | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 2 days |
| Part B - Cohort 3: KAF 400 mg and LUM 960 mg QD for 3 days | EXPERIMENTAL | Participants received KAF156 400 mg and LUM-SDF 960 mg once daily via oral administration for 3 days |
| Part B - Cohort 4: Coartem | ACTIVE_COMPARATOR | Participants received Coartem twice daily via oral administration for 3 days |
| Part 1 - Cohort 1: P. vivax: KAF156 400mg QD | EXPERIMENTAL | Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days. |
| Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD | EXPERIMENTAL | Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days. |
| Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose | EXPERIMENTAL | Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg. |
| KAF156 800 mg pre-challenge | EXPERIMENTAL | Single dose 800 mg KAF156 oral administration in healthy subjects, prior to exposure to P. falciparum sporozoite-infected mosquitos |
| Placebo 800 mg pre-challenge | PLACEBO_COMPARATOR | Single dose 800 mg placebo oral administration in healthy subjects, prior to exposure to P. falciiparum sporozoite-infected mosquitos |
| KAF156 800 mg post-challenge | EXPERIMENTAL | Single dose 800 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| Placebo 800 mg post-challenge | PLACEBO_COMPARATOR | Single dose 800 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| KAF156 300 mg post-challenge | EXPERIMENTAL | Single dose 300 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| Placebo 300 mg post-challenge | PLACEBO_COMPARATOR | Single dose 300 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| KAF156 100 mg post-challenge | EXPERIMENTAL | Single dose 100 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| Placebo 100 mg post-challenge | PLACEBO_COMPARATOR | Single dose 100 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| KAF156 20 mg post-challenge | EXPERIMENTAL | Single dose 20 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| Placebo 20 mg post-challenge | PLACEBO_COMPARATOR | Single dose 20 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| KAF156 50 mg post-challenge | EXPERIMENTAL | Single dose 50 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| Placebo 50 mg post-challenge | PLACEBO_COMPARATOR | Single dose 50 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos |
| Name | Type | Description |
|---|---|---|
| KAF156 | DRUG | Provided as 100 mg tablets, to be taken QD 2 or 3 Days in combination with LUM-SDF, dose is based on body weight |
| LUM-SDF | DRUG | Provided as 120 mg or 240 mg powder in sachet, to be taken QD 2 or 3 Days in combination with KAF156, dose is based on body weight |
| Coartem | DRUG | Coartem® (Artemether/Lumefantrine dispersible tablets 20/120mg in blister pack) (for Cohorts 1 and 2), dose is based on body weight |
| Lumefantrine Solid Dispersion Formulation | DRUG | LUM-SDF comes in 240 mg or 480 mg sachets for oral administration. LUM-SDF was administered in combination with KAF156 once daily (QD) for 1, 2 or 3 days at 480 mg or 960 mg doses. |
| Placebo | DRUG | 100 mg tablet, 20 mg tablet, 50 mg tablet |
Inclusion Criteria: 1. In run-in cohort: Male and female patients 12 to \< 18 years of age, with a body weight * 35.0 kg In Cohort 1: Male and female patients 2 to \< 12 years of age, with a body weight ≥ 10.0 kg In Cohort 2: Male and female patients 6 months to \< 2 years of age, with a body w...
KAF156 is an investigational small molecule being developed for malaria, specifically acute uncomplicated Plasmodium falciparum malaria and uncomplicated Plasmodium falciparum malaria. It has been studied in adults and children across multiple countries. KAF156 is not approved and remains in clinical development.
KAF156 is being developed by Novartis AG, traded on the New York Stock Exchange under the ticker NVS. Novartis is conducting clinical trials of KAF156 for malaria indications, including combinations with lumefantrine solid dispersion formulation.
KAF156 is in Phase 2 clinical development. It has completed two Phase 2 trials and one Phase 1 trial, with no active trials currently listed. KAF156 is investigational and has not been approved by regulatory authorities.
KAF156 has completed several clinical trials, including NCT01753323 in adults with malaria, NCT03167242 in adults and children with uncomplicated Plasmodium falciparum malaria, and NCT04546633 in pediatric patients. A Phase 1 challenge trial, NCT04072302, also completed.
KAF156 is a distinct investigational compound being studied alone and in combination with lumefantrine solid dispersion formulation (LUM-SDF) for malaria. It is not the same as lumefantrine itself, which is an established antimalarial drug used as the combination partner in trials.