Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LXE408 · 4 trials · 4 indications
Cure at Day 180 (D180) is defined as: * 100% re-epithelialization of ulcerated lesions (if any) or flattening and/or no signs of induration of non-ulcerated lesions (if any) up to and at D90 and, * no relapse by D180, and * no rescue therapy up to D180 * no death, regardless of cause, up to D180
The parasitological load will be measured using polymerase chain reaction (PCR) at 2 months, 4 months, and at 6 months. At each timepoint, multiple samples are evaluated. The participant will be considered negative at a visit if the parasite is not detectable in all samples at a visit and positive if the parasite level is detectable in at least one sample. Sustained parasitological clearance is achieved if participant is negative at all 3 visits.
Initial cure defined as clinical improvement of Visceral leishmaniasis (VL), absence of parasites in the spleen or bone marrow (microscopy), and no rescue therapy on or before Day 28.
To assess the safety and tolerability of of single and multiple ascending oral doses of LXE408.
| Arm | Type | Description |
|---|---|---|
| LXE408 BID for 14 days | EXPERIMENTAL | LXE408 BID for 14 days followed by placebo BID for 14 days. |
| LXE408 BID for 28 days | EXPERIMENTAL | - |
| Miltefosine 50 mg PO TID for 28 days | ACTIVE_COMPARATOR | - |
| LXE408 28 days | EXPERIMENTAL | LXE408 administered by oral route |
| LXE408 14 days and Placebo 14 days | EXPERIMENTAL | LXE408 administered by oral route, followed by Placebo administered by oral route |
| Placebo 28 days | PLACEBO_COMPARATOR | Placebo administered by oral route |
| Benznidazole 60 days | ACTIVE_COMPARATOR | Benznidazole administered by oral route |
| LXE408 short regimen | EXPERIMENTAL | LXE408 once daily for seven days (followed by 7 days of placebo). |
| LXE408 long regimen | EXPERIMENTAL | LXE408 once daily for 14 days |
| Standard of care | ACTIVE_COMPARATOR | AmBisome® 10 mg/kg IV single dose (SDA) |
| Part A - Single Ascending Dose (SAD): Cohort 1: LXE408/Placebo | EXPERIMENTAL | Participants received a single ascending dose of LXE408 or Placebo (fasted). |
| Part A - SAD: Cohort 2: LXE408 /Placebo | EXPERIMENTAL | Participants received a single ascending dose of LXE408 or Placebo (fasted). |
| Part A - SAD: Cohort 3a/b: LXE408/Placebo | EXPERIMENTAL | Participants received a single ascending dose of LXE408 or Placebo (fasted and fed). This Cohort is divided into 2 parts: fasted and fed. Participants treated in cohort 3a (fasted) are mandated to return for cohort 3b (Food Effect) after at least a 7-day washout period between dosings. |
| Part A - SAD: Cohort 4: LXE408/Placebo | EXPERIMENTAL | Participants received a single ascending dose of LXE408 or Placebo (fasted). |
| Part A - SAD: Cohort 5: LXE408/Placebo | EXPERIMENTAL | Participants received a single ascending dose of LXE408 or Placebo (fasted). |
| Part B - Multiple ascending Dose (MAD): Cohort 1: LXE408/Placebo | EXPERIMENTAL | Participants received multiple ascending doses of LXE408 once daily or Placebo. |
| Part B - MAD: Cohort 2: LXE408/Placebo | EXPERIMENTAL | Participants received multiple ascending doses of LXE408 once daily or Placebo. |
| Part B - MAD: Cohort 3: LXE408/Placebo | EXPERIMENTAL | Participants received multiple ascending doses of LXE408 mg once daily or Placebo. |
| Part B - MAD: Cohort 4: LXE408/Placebo | EXPERIMENTAL | Participants received multiple ascending doses of LXE408 once daily or Placebo. |
| Part B - MAD: Cohort 5 (mGFR cohort): LXE408/Placebo | EXPERIMENTAL | Participants in this Measured glomerular filtration rate (mGFR) cohort received multiple ascending doses of LXE408 and iohexol or Placebo and iohexol. |
| Part B - MAD: Cohort 6: LXE408/Placebo | EXPERIMENTAL | Participants received multiple ascending doses of LXE408 once daily or Placebo. |
| Name | Type | Description |
|---|---|---|
| LXE408 | DRUG | LXE408 film-coated tablets. |
| Miltefosine 50 MG Oral Capsule [Impavido] | DRUG | Each capsule contains 50 mg miltefosine in an opaque, red, hard gelatin capsule. Capsules are supplied in packs of 56 capsules sealed in 8 aluminum blister stripes, each containing 7 capsules. |
| Placebo to LXE408 | DRUG | Film-coated tablets. |
| Placebo | DRUG | Placebo administered by oral route |
| Benznidazole | DRUG | Benznidazole administered by oral route (administered as standard of care) |
| AmBisome® | DRUG | Sterile lyophilised powder in a 15 mL sterile clear glass vial |
| Iohexol | DRUG | Iohexol is a nonionic, water-soluble radiographic contrast medium with a molecular weight of 821.14 and is administered to the participant via intravenous (IV) injection. |
Inclusion Criteria: 1. Participant must be aged ≥18 years old and weighing \> 50kg 2. Participant with first episode of CL fulfilling the following characteristics: * ≤ 6 lesions * At least one lesion of \> 50 mm2 of area * a history of CL of no longer than 6 months 3. a diagnosis of CL c...
LXE408 is an investigational oral small molecule being developed for several parasitic infections: Chagas disease, localized cutaneous leishmaniasis, primary visceral leishmaniasis, and visceral leishmaniasis. It is in Phase 2 clinical development and is not yet approved for any indication.
LXE408 is being developed by Novartis AG, which trades under the ticker NVS. Novartis is running the clinical program across multiple sites in the Americas and India, including studies in Brazil, Panama, Argentina, Colombia, the United States, and India.
LXE408 is in Phase 2 clinical development. A Phase 1 first-in-human study in healthy subjects has been completed, and Phase 2 studies are ongoing or planned in Chagas disease, localized cutaneous leishmaniasis, and primary visceral leishmaniasis.
LXE408 has been studied in NCT07809919, a completed Phase 1 first-in-human study in 88 healthy subjects in the United States, and NCT05593666, a completed Phase 2 study in 101 patients with primary visceral leishmaniasis in India. Active or planned Phase 2 trials include NCT06632600 in chronic Chagas disease and NCT06997159 in localized cutaneous leishmaniasis.
No. LXE408 is an investigational drug and has not been approved by the FDA. It remains in clinical development, with Phase 2 trials ongoing or planned for Chagas disease and leishmaniasis indications.
LXE408 is an oral small molecule developed for parasitic infections including Chagas disease and leishmaniasis. It is administered orally and is being evaluated in placebo-controlled and active-controlled Phase 2 trials, including a study comparing two oral LXE408 regimens against oral miltefosine in localized cutaneous leishmaniasis.