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Semaglutide

Phase 2

Nonalcoholic Steatohepatitis | Small molecule | Metabolic |Gilead Sciences, Inc.|Last Updated: Nov 26, 2025

Success Probability

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials2
Total Enrollment566

FDA Designations

No designations recorded

Clinical trial landscape

Semaglutide · 2 trials · 1 indication

Phase 2 2
NCT04971785Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)Nonalcoholic Steatohepatitis
COMPLETED457 Analytics
NCT03987074Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)Nonalcoholic Steatohepatitis
COMPLETED109 Analytics
PHASE2COMPLETED
Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic SteatohepatitisUnlock trial analytics
PHASE2COMPLETED
Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic SteatohepatitisUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants Who Achieved ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 72 in Semaglutide (SEMA) + Cilofexor/Firsocostat (CILO/FIR) Fixed Dose Combination (FDC) Versus Placebo Groups
Week 72

Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. Clopper-Pearson method was used in outcome measure analysis in each arm. Percentages were rounded-off.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
First dose date up to Week 24 plus 30 days

Treatment-emergent adverse events (TEAEs) were defined as, any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. Participants were assessed for AEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
First dose date up to 24 weeks plus 30 days

Treatment-emergent laboratory abnormalities, defined as values that increase at least one toxicity grade from baseline at any time post-baseline up to and including the date of last dose of study drug plus 30 days, were summarized by treatment group. Graded laboratory abnormalities were defined using the grading scheme in the CTCAE 5.0.

Secondary Endpoints

Percentage of Participants Who Achieved ≥1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 72 in SEMA + CILO/FIR FDC Versus SEMA Alone
Week 72
Percentage of Participants With NASH Resolution Without Worsening in Fibrosis at Week 72 in SEMA + CILO/FIR FDC Versus Placebo Groups
Week 72
Percentage of Participants With NASH Resolution Without Worsening in Fibrosis In Participants Treated With SEMA + CILO/FIR FDC Versus CILO/FIR Alone Groups
Week 72
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
SEMA + CILO/FIR FDCEXPERIMENTALParticipants will receive semaglutide (SEMA) 3.0 mg/mL, once weekly and cilofexor and firsocostat (CILO/FIR) 30 mg/20 mg fixed-dose combination (FDC) tablet, once daily up to 72 weeks.
SEMA + PTM CILO/FIREXPERIMENTALParticipants will receive SEMA 3.0 mg/mL, once weekly and Placebo-To-Match (PTM) CILO/FIR FDC tablet, once daily up to 72 weeks.
PTM SEMA + CILO/FIR FDCEXPERIMENTALParticipants will receive PTM SEMA, once weekly and CILO/FIR 30 mg/20 mg FDC tablet, once daily up to 72 weeks.
PTM SEMA + PTM CILO/FIRPLACEBO_COMPARATORParticipants will receive PTM SEMA, once weekly and PTM CILO/FIR FDC tablet, once daily up to 72 weeks.
SemaglutideEXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks
Semaglutide + Firsocostat 20 mgEXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks
Semaglutide + Cilofexor 30 mgEXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks
Semaglutide + Cilofexor 100 mgEXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mgEXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks

Interventions

NameTypeDescription
Semaglutide (SEMA)DRUGAdministered as subcutaneous (SC) injection
Cilofexor (CILO)/Firsocostat (FIR)DRUGTablets administered orally
PTM SEMADRUGAdministered as SC injection
PTM CILO/FIRDRUGTablets administered orally
SemaglutideDRUGSolution administered subcutaneously with pre-filled PDS290 pen-injector once weekly
FirsocostatDRUGTablets administered orally once daily
CilofexorDRUGTablets administered orally once daily
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites242

Key Inclusion Criteria: * Liver biopsy consistent with cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH) in the opinion of the central reader. In individuals who have never had a liver biopsy, a screening liver biopsy may be performed. * Screening laboratory parameters as determined by the ...

Countries:United StatesAustraliaCanadaFranceJapanPuerto RicoSpain
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Frequently asked questions about Semaglutide

What is Semaglutide used for in Nonalcoholic Steatohepatitis?

Semaglutide is being investigated as a treatment for Nonalcoholic Steatohepatitis (NASH). It is in Phase 2 clinical development for this condition. The drug is being studied both as a monotherapy and in combination with other agents to evaluate its safety, tolerability, and efficacy in adults with NASH, including those with cirrhosis.

Who makes Semaglutide?

Semaglutide is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol GILD. The company is conducting clinical trials to evaluate the drug's potential as a treatment for Nonalcoholic Steatohepatitis.

What phase is Semaglutide in?

Semaglutide is currently in Phase 2 clinical development for Nonalcoholic Steatohepatitis. Two Phase 2 trials have been completed, with a total of 566 participants enrolled across studies. The drug remains investigational and has not yet been approved for this indication.

What clinical trials is Semaglutide in?

Semaglutide has been studied in two completed Phase 2 clinical trials. The first trial, NCT03987074, enrolled 109 participants in the United States to evaluate monotherapy and combination regimens in NASH. The second trial, NCT04971785, enrolled 457 participants across multiple countries to study semaglutide alone and in combination with cilofexor/firsocostat in adults with cirrhosis due to NASH.

What does Semaglutide target?

Semaglutide is a small molecule being developed for Nonalcoholic Steatohepatitis. Its specific molecular target has not been disclosed in the available clinical trial information. The drug is being evaluated for its effects on liver-related outcomes in patients with NASH.

Is Semaglutide the same as other NASH treatments?

Semaglutide is being studied as a distinct investigational agent for Nonalcoholic Steatohepatitis. In clinical trials, it has been evaluated both alone and in combination with cilofexor and firsocostat, which are separate drugs. No alternative names for semaglutide have been reported in the trial data.