Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Participants With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
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ClinicalTrials.gov Identifier: NCT04971785 |
Recruitment Status :
Recruiting
First Posted : July 21, 2021
Last Update Posted : March 1, 2023
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Condition or disease | Intervention/treatment | Phase |
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Nonalcoholic Steatohepatitis | Drug: Semaglutide (SEMA) Drug: Cilofexor (CILO)/Firsocostat (FIR) Drug: PTM SEMA Drug: PTM CILO/FIR | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 440 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 : | March 2024 |
Estimated Study Completion Date : | March 2024 |

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

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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 |
Key Inclusion Criteria:
- Liver biopsy consistent with cirrhosis (F4) due to NASH in the opinion of the central reader. In participants who have never had a liver biopsy, a screening liver biopsy may be performed
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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%
- 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
- 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 HBV infection (HBsAg positive), or Chronic HCV infection (HCV antibody and HCV RNA positive). Participants 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)
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Men who habitually drink greater than 21 units/week of alcohol or women who habitually drink greater than 14 units/week of alcohol (one unit is equivalent to 12 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 participants who have not completed a series of an authorized COVID-19 vaccination regimen prior to screening, a positive result for COVID-19 on SARS-CoV-2 RT-PCR test
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Contact: Gilead Clinical Study Information Center | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |

Study Director: | Gilead Study Director | Gilead Sciences |
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: | March 1, 2023 |
Last Verified: | February 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Fatty Liver Non-alcoholic Fatty Liver Disease Liver Diseases Digestive System Diseases |
Firsocostat Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |