Phase 2 · Semaglutide

WAYFIND trial results

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)

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 (percentage of participants), Week 72. SEMA + CILO/FIR FDC: 13.7; PTM SEMA + PTM CILO/FIR: 8.3.

Participants
457
Status
completed
Completed
2024-12-09
Sponsor
Gilead Sciences

As posted on ClinicalTrials.gov (NCT04971785), updated at source Nov 26, 2025. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What WAYFIND measured first

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 Groupspercentage of participants · Week 72 · number
SEMA + CILO/FIR FDCn=124PTM SEMA + PTM CILO/FIRn=84
13.7(8.2 to 21.0)8.3(3.4 to 16.4)
Side effects by arm

Side effects in WAYFIND

Percent of participants affected, All-cause mortality and Adverse events: Up to 72 weeks plus 35 days. The most common events the registry lists.

EventSEMA + CILO/FIR FDCSEMA + PTM CILO/FIRPTM SEMA + CILO/FIR FDCPTM SEMA + PTM CILO/FIR
Any serious event13.7%10.7%14.6%13.1%
Nausea47.6%40.2%23.6%22.6%
Diarrhoea27.4%20.5%13%17.9%
Constipation24.2%21.3%8.9%8.3%
Vomiting21.8%17.2%5.7%7.1%
Covid-1916.9%12.3%12.2%16.7%
Decreased appetite15.3%16.4%5.7%6%
Fatigue13.7%13.9%7.3%13.1%
Abdominal pain8.9%8.2%4.9%13.1%
Arthralgia6.5%4.9%9.8%13.1%
Hypoglycaemia11.3%3.3%2.4%6%
Gastrooesophageal reflux disease5.6%10.7%2.4%2.4%
Pruritus6.5%10.7%9.8%7.1%
Urinary tract infection10.5%4.9%6.5%3.6%
Upper respiratory tract infection5.6%3.3%9.8%4.8%
Headache5.6%9%9.8%3.6%
Dyspepsia9.7%1.6%3.3%3.6%
Abdominal pain upper5.6%9%4.9%9.5%
Dizziness5.6%8.2%7.3%9.5%
Back pain6.5%5.7%6.5%8.3%
Cough2.4%2.5%5.7%8.3%
Abdominal distension7.3%8.2%3.3%7.1%
Sinusitis6.5%6.6%3.3%7.1%
Hypertension2.4%0.8%2.4%7.1%
Bronchitis1.6%2.5%4.1%6%
Influenza0.8%1.6%2.4%6%
Secondary outcomes

What else it measured

Percentage of Participants Who Achieved ≥1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 72 in SEMA + CILO/FIR FDC Versus SEMA Alonepercentage of participants · Week 72 · number
SEMA + CILO/FIR FDCn=124SEMA + PTM CILO/FIRn=122
13.7(8.2 to 21.0)15.6(9.6 to 23.2)
Percentage of Participants With NASH Resolution Without Worsening in Fibrosis at Week 72 in SEMA + CILO/FIR FDC Versus Placebo Groupspercentage of participants · Week 72 · number
SEMA + CILO/FIR FDCn=82PTM SEMA + PTM CILO/FIRn=49
57.3(45.9 to 68.2)22.4(11.8 to 36.6)
Percentage of Participants With NASH Resolution Without Worsening in Fibrosis In Participants Treated With SEMA + CILO/FIR FDC Versus CILO/FIR Alone Groupspercentage of participants · Week 72 · number
SEMA + CILO/FIR FDCn=82PTM SEMA + CILO/FIR FDCn=88
57.3(45.9 to 68.2)31.8(22.3 to 42.6)
The trial

How WAYFIND was run

The goal of this clinical study is to understand whether the study drugs, semaglutide (SEMA) with the fixed-dose combination (FDC) of cilofexor/firsocostat (CILO/FIR), cause fibrosis improvement and Nonalcoholic Steatohepatitis (NASH) resolution in participants with cirrhosis due to NASH.

  • SEMA + CILO/FIR FDC: Participants 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/FIR: Participants 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 FDC: Participants 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/FIR: Participants will receive PTM SEMA, once weekly and PTM CILO/FIR FDC tablet, once daily up to 72 weeks.
Who could join the trial

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...

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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