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

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ClinicalTrials.gov Identifier: NCT04971785
Recruitment Status : Active, not recruiting
First Posted : July 21, 2021
Last Update Posted : February 28, 2024
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Brief Summary:
The goals of this clinical study are to learn more about the study drugs, semaglutide (SEMA) with the fixed-dose combination (FDC) of cilofexor/firsocostat (CILO/FIR), and understand whether they cause fibrosis improvement and Nonalcoholic Steatohepatitis (NASH) resolution in participants with cirrhosis due to NASH.

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis Drug: Semaglutide (SEMA) Drug: Cilofexor (CILO)/Firsocostat (FIR) Drug: PTM SEMA Drug: PTM CILO/FIR Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 457 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : August 9, 2021
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Semaglutide

Arms and Interventions
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Arm Intervention/treatment
Experimental: SEMA + CILO/FIR FDC
Participants will receive semaglutide (SEMA) 0.24-2.4 mg once weekly (dose escalation every 4 weeks) and fixed-dose combination (FDC) of cilofexor and firsocostat (CILO/FIR 30 mg/20 mg) once daily for 72 weeks
 Drug: Semaglutide (SEMA)
Administered as subcutaneous (SC) injection

Drug: Cilofexor (CILO)/Firsocostat (FIR)
Tablets administered orally
Other Name: GS-9674/GS-0976
Experimental: SEMA + Placebo-To-Match (PTM) CILO/FIR
Participants will receive SEMA 0.24-2.4 mg once weekly (dose escalation every 4 weeks) and PTM CILO/FIR administered once daily for 72 weeks
 Drug: Semaglutide (SEMA)
Administered as subcutaneous (SC) injection

Drug: PTM CILO/FIR
Tablets administered orally
Experimental: PTM SEMA + CILO/FIR FDC
PTM Semaglutide once weekly and CILO/FIR 30 mg/20 mg FDC administered once daily for 72 weeks
 Drug: Cilofexor (CILO)/Firsocostat (FIR)
Tablets administered orally
Other Name: GS-9674/GS-0976

Drug: PTM SEMA
Administered as SC injection
Placebo Comparator: PTM SEMA + PTM CILO/FIR
PTM Semaglutide once weekly and PTM CILO/FIR once daily for 72 weeks
 Drug: PTM SEMA
Administered as SC injection

Drug: PTM CILO/FIR
Tablets administered orally


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants Who Achieve ≥ 1-Stage Improvement in Fibrosis According to the NASH Clinical Research Network (CRN) Classification Without Worsening of NASH in Participants Treated With SEMA + CILO/FIR Versus Placebo [ Time Frame: Week 72 ]
    Worsening of NASH is defined as a ≥ 1-point increase in hepatocellular ballooning or lobular inflammation.


Secondary Outcome Measures :
  1. Percentage of Participants Who Achieve ≥1-Stage Improvement in Fibrosis (According to the NASH CRN Classification) Without Worsening of NASH in Participants Treated With SEMA+CILO/FIR Versus SEMA Alone [ Time Frame: Week 72 ]
    Worsening of NASH is defined as a ≥ 1-point increase in hepatocellular ballooning or lobular inflammation.

  2. Percentage of Participants With NASH Resolution in Participants Treated with SEMA+CILO/FIR Versus Placebo [ Time Frame: Week 72 ]
    NASH resolution is defined as lobular inflammation of 0 or 1 and hepatocellular ballooning of 0.

  3. Percentage of Participants With NASH Resolution In Participants Treated With SEMA+CILO/FIR Versus CILO/FIR Alone [ Time Frame: Week 72 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/1.73m^2, as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
    • HbA1c ≤ 10%
    • International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation
    • Platelet count ≥ 125,000/uL
    • Alanine aminotransferase (ALT) < 5 x 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 coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) test.

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04971785


Locations
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Sponsors and Collaborators
Gilead Sciences
Novo Nordisk A/S
Investigators
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Study Director: Gilead Study Director Gilead Sciences
More Information
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Additional Information:

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04971785    
Other Study ID Numbers: GS-US-454-6075
2021-001445-12 ( EudraCT Number )
jRCT2071210112 ( Registry Identifier: jRCT )
First Posted: July 21, 2021    Key Record Dates
Last Update Posted: February 28, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Semaglutide
Firsocostat
 Glucagon-Like Peptide-1 Receptor Agonists
Hypoglycemic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action