Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GS-4997
SEL · 4 trials · 5 indications
The values of eGFRcr were calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2009). eGFRcr = 141\*min(Standardized Serum Creatinine (Scr)/kappa, 1) \^alpha\*max(Scr/ kappa, 1)\^(-1.209)\*0.993\^Age\*1.018\[if female\]\*1.159\[if Black\], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment-specific Baselines = the average of Visits A and B values for Placebo, and the average of Visit C and Day 1 values for SEL. Visit A= enrollment, Visit B= 7-14 days after Visit A, Visit C= 21-28 days after Visit B, and Visit 1= 7-14 days after Visit C.
The values of eGFRcr were calculated using the CKD-EPI Creatinine Equation (2009). eGFRcr = 141\*min(Scr/kappa, 1) \^alpha\*max(Scr/kappa, 1)\^(-1.209)\*0.993\^Age\*1.018\[if female\]\*1.159\[if Black\], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment specific baselines for eGFRcr: average of Visit A (enrollment) and Visit B (7-14 days after Visit A) values for Placebo, and average of Visit C (21-28 days after Visit B, and Visit 1 (7-14 days after Visit C) values for SEL.
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network classification (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. The 95% CI was based on the Clopper-Pearson method.
Treatment-emergent AEs were defined as events that met 1 or both of the following criteria: * Any AEs with onset dates on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug * Any AEs leading to premature discontinuation of study drug
A treatment emergent serious adverse event (SAE) was defined as an event that, at any dose, results in the following: * Death * Life-threatening * In-patient hospitalization or prolongation of existing hospitalization * Persistent or significant disability/incapacity * A congenital anomaly/birth defect * A medically important event or reaction
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days for subjects who permanently discontinued study drug. If baseline laboratory data were missing, then any abnormality of at least Grade 1 was considered treatment emergent. Graded laboratory abnormalities were defined using the grading scheme in the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 for Cohorts 1-9 and CTCAE Version 5.0 for Cohorts 10-13.
Treatment-emergent events began on or after the first dosing date up to 30 days after the last dosing date or led to premature discontinuation of study drug. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
| Arm | Type | Description |
|---|---|---|
| Selonsertib | EXPERIMENTAL | Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks. |
| Placebo | PLACEBO_COMPARATOR | Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks. |
| Selonsertib (SEL) | EXPERIMENTAL | Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks. |
| Firsocostat (FIR) | EXPERIMENTAL | Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. |
| Cilofexor (CILO) | EXPERIMENTAL | Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. |
| Selonsertib (SEL) + Firsocostat (FIR) | EXPERIMENTAL | Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. |
| Selonsertib (SEL) + Cilofexor (CILO) | EXPERIMENTAL | Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. |
| Firsocostat (FIR) + Cilofexor (CILO) | EXPERIMENTAL | Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks. |
| Cohort 1: SEL 18 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive selonsertib (SEL) 18 mg tablet orally once daily for 12 weeks. |
| Cohort 2: FIR 20 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive firsocostat (FIR) 20 mg tablet orally once daily for 12 weeks. |
| Cohort 3: CILO 30 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive cilofexor (CILO) 30 mg tablet once daily for 12 weeks. |
| Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive SEL 18 mg tablet + CILO 30 mg tablet once daily for 12 weeks. |
| Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive SEL 18 mg tablet + FIR 20 mg tablet once daily for 12 weeks. |
| Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive CILO 30 mg tablet + FIR 20 mg tablet once daily for 12 weeks. |
| Cohort 7: CILO 20 mg (Cirrhotic) | EXPERIMENTAL | Participants with Child-Pugh-Turcotte Class A cirrhosis will receive FIR 20 mg tablet once daily for 12 weeks. |
| Cohort 8: CILO 30 mg (Cirrhotic) | EXPERIMENTAL | Participants with Child-Pugh-Turcotte Class A cirrhosis will receive CILO 30 mg tablet once daily for 12 weeks. |
| Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic) | EXPERIMENTAL | Non-cirrhotic participants will receive SEL 18 mg tablet + FIR 20 mg tablet + CILO 30 mg tablet once daily for 12 weeks. |
| Cohort 10: FIR 20 mg + FENO 48 mg | EXPERIMENTAL | Participants will receive fenofibrate (FENO) 48 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet + FENO 48 mg tablet orally once daily for 24 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| Cohort 11: FIR 20 mg + FENO 145 mg | EXPERIMENTAL | Participants will receive FENO 145 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet + FENO 145 mg tablet orally once daily for 24 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g | EXPERIMENTAL | Participants will receive Vascepa® (VAS) 2 g capsule orally twice daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet once daily + CILO 30 mg tablet once daily + VAS 2 g capsule twice daily for 6 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg | EXPERIMENTAL | Participants will receive FENO 145 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet once daily + CILO 30 mg tablet once daily + FENO 145 mg tablet orally once daily for 6 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| SEL 6 mg | EXPERIMENTAL | Selonsertib (SEL) 6 mg for 24 weeks. |
| SEL 18 mg | EXPERIMENTAL | SEL 18 mg for 24 weeks. |
| SEL 6 mg+SIM 125 mg | EXPERIMENTAL | SEL 6 mg plus SIM 125 mg for 24 weeks. |
| SEL 18 mg+SIM 125 mg | EXPERIMENTAL | SEL 18 mg plus SIM 125 mg for 24 weeks. |
| SIM 125 mg | EXPERIMENTAL | SIM 125 mg for 24 weeks. |
| Name | Type | Description |
|---|---|---|
| SEL | DRUG | Tablet administered orally once daily |
| Placebo | DRUG | Tablet administered orally once daily |
| FIR | DRUG | 20 mg tablet administered orally once daily without regard to food |
| CILO | DRUG | 30 mg tablet administered orally once daily without regard to food |
| Placebo to match FIR | DRUG | Tablet administered orally once daily without regard to food |
| Placebo to match CILO | DRUG | Tablet administered orally once daily without regard to food |
| Placebo to match SEL | DRUG | Tablet administered orally once daily without regard to food |
| FENO | DRUG | Administered orally once daily |
| VAS | DRUG | Administered orally two times daily |
| SIM | BIOLOGICAL | Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly |
Key Inclusion Criteria: * Diagnosis of type 2 diabetes mellitus (T2DM) as per local guidelines. * Estimated glomerular filtration rate (eGFR) value calculated by central laboratory utilizing samples collected during screening and prior to enrollment of ≥ 20 mL/min/1.73 m\^2 to \< 60 mL/min/1.73 m\^...
Selonsertib is an investigational small molecule developed by Gilead Sciences for liver and kidney diseases. It has been studied in Phase 2 clinical trials for nonalcoholic steatohepatitis, also called NASH, and for diabetic kidney disease. It is not an approved medicine and remains in clinical development.
Selonsertib was studied in Phase 2 trials as a treatment for nonalcoholic steatohepatitis, or NASH, including patients with bridging fibrosis or compensated cirrhosis. Some studies tested it alone and others combined it with firsocostat or cilofexor. These trials are completed, and selonsertib is not approved for NASH.
Selonsertib was evaluated in a Phase 2 trial in adults with moderate to advanced diabetic kidney disease. That study, NCT04026165, enrolled 384 participants across the United States, Australia, Canada, Japan, and New Zealand and is completed. Selonsertib is investigational and has no approved indication in diabetic kidney disease.
Selonsertib is developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead sponsored the Phase 2 clinical program testing selonsertib in nonalcoholic steatohepatitis and diabetic kidney disease.
Selonsertib is in Phase 2. All of its listed clinical trials are Phase 2 studies, and all are completed, with no active trials currently listed. Selonsertib is an investigational drug and is not FDA approved for any indication.
Selonsertib has been tested in completed Phase 2 trials including NCT04026165 in diabetic kidney disease, NCT03449446 and NCT02781584 in NASH, and NCT02466516 in NASH with fibrosis stages F2 to F3. These randomized, double-blind, placebo-controlled studies enrolled adults and are all completed.