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SEL

Phase 2

Diabetic Kidney Disease | Small molecule | Nephrology |Gilead Sciences, Inc.|Last Updated: Dec 21, 2022

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment384

FDA Designations

No designations recorded

Clinical trial landscape

SEL · 4 trials · 5 indications

Phase 2 4
NCT04026165Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney DiseaseDiabetic Kidney Disease
COMPLETED384 Analytics
NCT03449446Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)Nonalcoholic Steatohepatitis
COMPLETED395 Analytics
NCT02781584Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)Nonalcoholic Steatohepatitis (NASH)
COMPLETED220 Analytics
NCT02466516Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Adults With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3Non-Alcoholic Steatohepatitis (NASH)
COMPLETED72 Analytics
PHASE2COMPLETED
Study to Evaluate the Efficacy and Safety of Selonsertib in Participants With Moderate to Advanced Diabetic Kidney Disease
Diabetic Kidney DiseaseUnlock trial analytics
PHASE2COMPLETED
Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic SteatohepatitisUnlock trial analytics
PHASE2COMPLETED
Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic Steatohepatitis (NASH)Unlock trial analytics
PHASE2COMPLETED
Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Adults With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3
Non-Alcoholic Steatohepatitis (NASH)Unlock trial analytics

Study Endpoints

Primary Endpoints

Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)
Treatment-specific Baselines (From enrollment (Visit A) up to 14 days after Visit A for placebo and from Visit C up to 14 days after Visit C for SEL)

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.

eGFRcr Slope
Treatment-specific Baselines through Week 84

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.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
First dose date up to 48 weeks plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
First dose date up to 48 weeks plus 30 days

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48
Week 48

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.

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.

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

Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events
Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.

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

Percentage of Participants Who Experienced Grade 3 or Higher Laboratory Abnormalities
Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.

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.

Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality
Baseline up to last dose plus 30 days (up to Week 28)

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.

Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events
Baseline up to follow up visit (Week 28)

Secondary Endpoints

Percentage of Participants With Kidney Clinical Events at Week 48
Week 48
Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event
From randomization up to Week 101
Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys)
Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values)
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
SelonsertibEXPERIMENTALRun-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.
PlaceboPLACEBO_COMPARATORRun-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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
Selonsertib (SEL) + Cilofexor (CILO)EXPERIMENTALParticipants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
Firsocostat (FIR) + Cilofexor (CILO)EXPERIMENTALParticipants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.
Cohort 1: SEL 18 mg (Non-cirrhotic)EXPERIMENTALNon-cirrhotic participants will receive selonsertib (SEL) 18 mg tablet orally once daily for 12 weeks.
Cohort 2: FIR 20 mg (Non-cirrhotic)EXPERIMENTALNon-cirrhotic participants will receive firsocostat (FIR) 20 mg tablet orally once daily for 12 weeks.
Cohort 3: CILO 30 mg (Non-cirrhotic)EXPERIMENTALNon-cirrhotic participants will receive cilofexor (CILO) 30 mg tablet once daily for 12 weeks.
Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic)EXPERIMENTALNon-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)EXPERIMENTALNon-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)EXPERIMENTALNon-cirrhotic participants will receive CILO 30 mg tablet + FIR 20 mg tablet once daily for 12 weeks.
Cohort 7: CILO 20 mg (Cirrhotic)EXPERIMENTALParticipants with Child-Pugh-Turcotte Class A cirrhosis will receive FIR 20 mg tablet once daily for 12 weeks.
Cohort 8: CILO 30 mg (Cirrhotic)EXPERIMENTALParticipants 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)EXPERIMENTALNon-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 mgEXPERIMENTALParticipants 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 mgEXPERIMENTALParticipants 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 2gEXPERIMENTALParticipants 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 mgEXPERIMENTALParticipants 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 mgEXPERIMENTALSelonsertib (SEL) 6 mg for 24 weeks.
SEL 18 mgEXPERIMENTALSEL 18 mg for 24 weeks.
SEL 6 mg+SIM 125 mgEXPERIMENTALSEL 6 mg plus SIM 125 mg for 24 weeks.
SEL 18 mg+SIM 125 mgEXPERIMENTALSEL 18 mg plus SIM 125 mg for 24 weeks.
SIM 125 mgEXPERIMENTALSIM 125 mg for 24 weeks.

Interventions

NameTypeDescription
SELDRUGTablet administered orally once daily
PlaceboDRUGTablet administered orally once daily
FIRDRUG20 mg tablet administered orally once daily without regard to food
CILODRUG30 mg tablet administered orally once daily without regard to food
Placebo to match FIRDRUGTablet administered orally once daily without regard to food
Placebo to match CILODRUGTablet administered orally once daily without regard to food
Placebo to match SELDRUGTablet administered orally once daily without regard to food
FENODRUGAdministered orally once daily
VASDRUGAdministered orally two times daily
SIMBIOLOGICALSimtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites111

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\^...

Countries:United StatesAustraliaCanadaJapanNew ZealandHong KongPuerto Rico
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Frequently asked questions about SEL

What is SEL used for?

SEL, also known as selonsertib, is an investigational small molecule being studied for nonalcoholic steatohepatitis (NASH), including in patients with fibrosis stages F2-F3 and bridging fibrosis or compensated cirrhosis, as well as for diabetic kidney disease. It is in Phase 2 clinical development and is not yet approved.

What does SEL target?

SEL is an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. By inhibiting ASK1, it is designed to reduce oxidative stress, inflammation, and fibrosis in the liver and kidney. This mechanism is being evaluated in conditions such as NASH and diabetic kidney disease.

Who makes SEL?

SEL is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on NASDAQ under the ticker GILD. Gilead is conducting Phase 2 clinical trials to evaluate the safety and efficacy of SEL in NASH and diabetic kidney disease.

What phase is SEL in?

SEL is in Phase 2 clinical development. It has completed multiple Phase 2 trials in NASH and diabetic kidney disease, but it remains investigational and has not been approved by regulatory authorities. All listed trials for SEL are completed, with no active trials currently registered.

What clinical trials is SEL in?

SEL has been studied in several completed Phase 2 trials, including NCT02466516 in NASH with fibrosis F2-F3, NCT02781584 in NASH, NCT03449446 in NASH with bridging fibrosis or compensated cirrhosis, and NCT04026165 in diabetic kidney disease. These trials enrolled adults aged 18 and older.

Is SEL the same as selonsertib?

Yes, SEL is the same as selonsertib. In clinical trials, selonsertib has been evaluated alone or in combination with other investigational drugs such as simtuzumab, firsocostat, and cilofexor for the treatment of NASH and diabetic kidney disease.