WAYFIND

CompletedPhase 2Results posted

Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)

A Phase 2, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Subjects With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Lead sponsor

Gilead Sciences

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

242

Recruiting sites

—

Enrollment

457

actual

Study population

MASH / NAFLD / liver fibrosis

Key I/E criteria

•BMI ≥23•HbA1c ≤10%•eGFR ≥30

Primary endpoint

•Fibrosis ≥1-stage improvement, no MASH worsening

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04971785

Org study IDGS-US-454-6075

Secondary ID2021-001445-12

Secondary IDjRCT2071210112Japan Registry of Clinical Trials

Timeline

Milestones

Study first posted2021-07-21actual

Study start2021-08-09actual

Primary completion2024-11-12actual

Study completion2024-12-09actual

Last update posted2025-11-26actual

Results first posted2025-11-26actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosis

Eligibility

Who can enroll

Minimum age18 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

Eligibility criteria

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 study central laboratory:

–Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m^2, as calculated by the Modification of Diet in Renal Disease (MDRD) equation.

–Hemoglobin A1c (HbA1c) ≤ 10%

–International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation

–Platelet count ≥ 125,000/µL

–Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)

–Serum albumin ≥ 3.5 g/dL

–Serum alkaline phosphatase (ALP) ≤ 2 x ULN

•Body mass index (BMI) ≥ 23 kg/m^2 at screening.

Key Exclusion Criteria:

•Prior history of decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal bleeding.

•Child-Pugh (CP) score > 6 at screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation.

•Model for End-stage Liver Disease (MELD) score > 12 at screening, unless due to an alternative etiology such as therapeutic anticoagulation.

•Other causes of liver disease based on medical history and/or central reader review of liver histology, including but not limited to: alcoholic liver disease, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency.

•Chronic hepatitis B virus (HBV) infection (HBsAg positive), or Chronic hepatitis C virus (HCV) infection (HCV antibody and HCV ribonucleic acid (RNA) positive). Individuals cured of HCV infection less than 2 years prior to the screening visit are not eligible.

•History of liver transplantation.

•Current or prior history of hepatocellular carcinoma (HCC).

•Men who habitually drink greater than 21 units/week of alcohol or women who habitually drink greater than 14 units/week of alcohol (1 unit is equivalent to 12 ounce (oz)/360 mL of beer, a 4 oz/120 mL glass of wine, or 1 oz/30 mL of hard liquor).

–For individuals on vitamin E regimen ≥ 800 IU/day, or pioglitazone, dose must be stable, in the opinion of the investigator for at least 180 days prior to the historical or screening liver biopsy.

–For individuals on medications for diabetes, dose must be stable, in the opinion of the investigator, for at least 90 days prior to the historical or screening liver biopsy.

•History of type 1 diabetes.

•Treatment with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in the period from 90 days prior to the screening visit and for individuals with a qualifying historical liver biopsy, for 90 days prior to the date of the historical liver biopsy.

•For individuals who have not completed a series of an authorized coronavirus disease 2019 (COVID-19) vaccination regimen prior to screening, a positive result for COVID-19 on severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) test.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

MASH / liver

8 endpoints

Primary/registry result

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

Time frame:Week 72

Fibrosis ≥1-stage improvement, no MASH worsening

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	95% CI
SEMA + CILO/FIR FDC	13.7	8.2 – 21.0
PTM SEMA + PTM CILO/FIR	8.3	3.4 – 16.4

Difference in percentages5.795% CI-3.6 – 14.9p0.2289Stratified Mantel-Haenszel test

Primary/protocol endpoint

Time frame:Week 72

Fibrosis ≥1-stage improvement, no MASH worsening

threshold achievement, improvement

Secondary/registry result

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

Time frame:Week 72

Fibrosis ≥1-stage improvement, no MASH worsening

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	95% CI
SEMA + CILO/FIR FDC	13.7	8.2 – 21.0
SEMA + PTM CILO/FIR	15.6	9.6 – 23.2

Difference in percentages-1.895% CI-11.1 – 7.4p0.6959Stratified Mantel-Haenszel test

Secondary/registry result

Percentage of Participants With NASH Resolution Without Worsening in Fibrosis at Week 72 in SEMA + CILO/FIR FDC Versus Placebo Groups

Time frame:Week 72

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Posted result

Group	Value (number), percentage of participants	95% CI
SEMA + CILO/FIR FDC	57.3	45.9 – 68.2
PTM SEMA + PTM CILO/FIR	22.4	11.8 – 36.6

Difference in percentages35.795% CI18.8 – 52.6p<0.0001Stratified Mantel-Haenszel test

Secondary/registry result

Percentage of Participants With NASH Resolution Without Worsening in Fibrosis In Participants Treated With SEMA + CILO/FIR FDC Versus CILO/FIR Alone Groups

Time frame:Week 72

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Posted result

Group	Value (number), percentage of participants	95% CI
SEMA + CILO/FIR FDC	57.3	45.9 – 68.2
PTM SEMA + CILO/FIR FDC	31.8	22.3 – 42.6

Difference in percentages26.195% CI11.3 – 40.9p0.0006Stratified Mantel-Haenszel test

Secondary/protocol endpoint

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

Time frame:Week 72

Fibrosis ≥1-stage improvement, no MASH worsening

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants With NASH Resolution Without Worsening in Fibrosis at Week 72 in SEMA + CILO/FIR FDC Versus Placebo Groups

Time frame:Week 72

MASH resolution, no fibrosis worsening

categorical status, improvement

Secondary/protocol endpoint

Percentage of Participants With NASH Resolution Without Worsening in Fibrosis In Participants Treated With SEMA + CILO/FIR FDC Versus CILO/FIR Alone Groups

Time frame:Week 72

MASH resolution, no fibrosis worsening

categorical status, improvement

SNOMED 442685003

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Pharmacokinetics and Safety of Cilofexor and Firsocostat in Healthy Japanese and Non-Japanese Participants.
Journal of clinical pharmacology2024 Dec (month)PMID39213138doi:10.1002/jcph.6114via pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.