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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)

Sponsor
Gilead Sciences (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04971785
Collaborator
Novo Nordisk A/S (Industry)
440
Enrollment
159
Locations
4
Arms
30.7
Anticipated Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate whether the combination of semaglutide (SEMA) with the fixed-dose combination (FDC) of cilofexor/firsocostat (CILO/FIR) causes fibrosis improvement and Nonalcoholic Steatohepatitis (NASH) resolution in participants with compensated cirrhosis due to NASH.

Condition or Disease Intervention/Treatment Phase
  • Drug: Semaglutide (SEMA)
  • Drug: Cilofexor (CILO)/Firsocostat (FIR)
  • Drug: PTM SEMA
  • Drug: PTM CILO/FIR
 Phase 2

Study Design

Study Type:
Interventional
Anticipated 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 :
Aug 9, 2021
Anticipated Primary Completion Date :
Mar 1, 2024
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

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 Names:
  • 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 Names:
  • 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

    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 [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 [Week 72]

      NASH resolution is defined as lobular inflammation of 0 or 1 and hepatocellular ballooning of 0.

    Secondary Outcome Measures

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

    2. 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 [Week 72]

      Worsening of NASH is defined as a ≥ 1-point increase in hepatocellular ballooning or lobular inflammation.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    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

    • 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)

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Hospital Birmingham Alabama United States 35233
    2 Digestive Health Specialists Dothan Alabama United States 36305
    3 North Alabama Health Research, LLC Madison Alabama United States 35758
    4 The Institution For Liver Health dba Arizona Liver Health Chandler Arizona United States 85224
    5 The Institute for Liver Health DBA Arizona Liver Health Peoria Arizona United States 85381
    6 Adobe Clinical Research, LLC Tucson Arizona United States 85712
    7 The Institution For Liver Health dba Arizona Liver Health Tucson Arizona United States 85712
    8 Arkansas Diagnostic Center Little Rock Arkansas United States 72204
    9 ARCare Center for Clinical Research Little Rock Arkansas United States 72205
    10 Southern California Research Center Coronado California United States 92118
    11 University of California, San Diego - Altman Clinical and Translational Research Institute La Jolla California United States 92037
    12 Digestive Health Research of Southern California Long Beach California United States 90808
    13 Kaiser Permanente Los Angeles Medical Center Los Angeles California United States 90027
    14 Keck Medical Center of USC Healthcare Consultation II Los Angeles California United States 90033
    15 United Medical Doctors Murrieta California United States 92563
    16 Knowledge Research Center Orange California United States 92868
    17 California Liver Research Institute Pasadena California United States 91105
    18 Cadena Care Institute, LLC Poway California United States 92064
    19 Stanford Medicine Outpatient Center Redwood City California United States 94063
    20 Inland Empire Clinical Trials Rialto California United States 92377
    21 University of California, Davis Medical Center Sacramento California United States 95817
    22 Research and Education Inc. San Diego California United States 92105
    23 TriWest Research Associates, LLC San Diego California United States 92108
    24 Precision Research Institute San Diego California United States 92114
    25 Medical Associates Research Group San Diego California United States 92123
    26 Quest Clinical Research San Francisco California United States 94115
    27 University of California, San Francisco - Liver Clinic San Francisco California United States 94143
    28 University of Colorado Anschutz Medical Campus Aurora Colorado United States 80045
    29 South Denver Gastroenterology Englewood Colorado United States 80113
    30 Excel Medical Clinical Trials, LLC Boca Raton Florida United States 33434
    31 University of Florida Hepatology Research at the Clinical and Translational Research Building Gainesville Florida United States 32610
    32 Indago Research and Health Center, Inc. Hialeah Florida United States 33012
    33 Nature Coast Clinical Research Inverness Florida United States 34452
    34 UF Health Jacksonville-Gastroenterology Emerson Jacksonville Florida United States 32207
    35 Florida Research Institute Lakewood Ranch Florida United States 34211
    36 Ocean Blue Medical Research Center, Inc Miami Springs Florida United States 33166
    37 Schiff Center for Liver Diseases/ University of Miami Miami Florida United States 33136
    38 Advanced Pharma CR, LLC Miami Florida United States 33147
    39 ProLive Medical Research, Corp Miami Florida United States 33175
    40 Advanced Research Institute, Inc. New Port Richey Florida United States 34653
    41 Ocala GI Research Ocala Florida United States 34471
    42 International Medical Investigational Centers, Inc. Palmetto Bay Florida United States 33157
    43 Advanced Medical Research Center Port Orange Florida United States 32127
    44 Covenant Metabolic Specialists, LLC Sarasota Florida United States 34240
    45 Florida Medical Clinic, LLC Zephyrhills Florida United States 33542
    46 Gastrointestinal (GI) Specialists of Georgia Marietta Georgia United States 30060
    47 Rush University Medical Group - Department of Hepatology Chicago Illinois United States 60612
    48 Indiana University Health Enterprise Clinical Research Operations Indianapolis Indiana United States 46202
    49 Digestive Research Alliance of Michigan South Bend Indiana United States 44635
    50 Iowa Digestive Disease Center, PC Clive Iowa United States 50325
    51 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    52 University of Kansas Medical Center Kansas City Kansas United States 66160
    53 Kansas Medical Clinic PA Topeka Kansas United States 66606
    54 Tandem Clinical Research GI, LLC Marrero Louisiana United States 70072
    55 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    56 Oschner Clinic Foundation New Orleans Louisiana United States 70121
    57 Louisiana Research Center, LLC Shreveport Louisiana United States 71105
    58 Mercy Medical Center Baltimore Maryland United States 21202
    59 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    60 Greater Boston Gastroenterology Framingham Massachusetts United States 01702
    61 Hawthorn Medical Associates South Dartmouth Massachusetts United States 02747
    62 Henry Ford Health System Detroit Michigan United States 48202
    63 Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center Wyoming Michigan United States 49519
    64 Huron Gastroenterology Associates Ypsilanti Michigan United States 48197
    65 GI Alliance Flowood Mississippi United States 39232
    66 Southern Therapy and Advanced Research Jackson Mississippi United States 39216
    67 Clinical Research Professionals Chesterfield Missouri United States 63005
    68 GI Associates Research Columbia Missouri United States 65201
    69 Sierra Clinical Research Las Vegas Nevada United States 89106
    70 Digestive Disease Research Florham Park New Jersey United States 07932
    71 Center for Research at Southwest Gastroenterology Associates, PC Albuquerque New Mexico United States 87109
    72 Northwell Health Center for Liver Diseases Manhasset New York United States 11030
    73 The New York - Presbyterian Hospital New York New York United States 10065
    74 University of Rochester Medical Center Rochester New York United States 14642
    75 Asheville Gastroenterology, a Division of Digestive Health Partners, PA Asheville North Carolina United States 28801
    76 Atrium Health Transplant and Center for Liver Disease Charlotte North Carolina United States 28204
    77 Charlotte Gastroenterology & Hepatology, PLLC Charlotte North Carolina United States 28207
    78 Northeast GI Research Division Concord North Carolina United States 28027
    79 Lucas Research, Inc. Morehead City North Carolina United States 28557
    80 Carolina's GI Research, LLC Raleigh North Carolina United States 27607
    81 DSI Research Springboro Ohio United States 45066
    82 Clinical Research Institute of Ohio, LLC Westlake Ohio United States 44145
    83 Options Health Research, LLC Tulsa Oklahoma United States 74104
    84 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213
    85 Velocity Clinical Research - Providence East Greenwich Rhode Island United States 02818
    86 University Gastroenterology Providence Rhode Island United States 02905
    87 Medical University of South Carolina Charleston South Carolina United States 29425
    88 Digestive Disease Research Center Greenwood South Carolina United States 29646
    89 Wake Research - ClinsSearch, LLC Chattanooga Tennessee United States 37421
    90 Quality Medical Research, PLLC Nashville Tennessee United States 37211
    91 Texas Clinical Research Institute Arlington Texas United States 76012
    92 The Liver Institute at Methodist Dallas Medical Center Dallas Texas United States 75203
    93 GI Alliance Dallas Texas United States 75246
    94 Internal Medicine Digestive and Liver Diseases Clinical Trials Dallas Texas United States 75390
    95 South Texas Research Institute Edinburg Texas United States 78539
    96 American Research Corporation at the Texas Liver Institute San Antonio Texas United States 78215
    97 Diabetes and Glandular Disease Clinic, P.A. San Antonio Texas United States 78229
    98 Impact Research Institute Waco Texas United States 76710
    99 Digestive Health Research of North Texas Wichita Falls Texas United States 07960
    100 Intermountain Medical Center Murray Utah United States 84107
    101 University of Utah Hospital Salt Lake City Utah United States 84132
    102 University of Virginia Medical Center Charlottesville Virginia United States 22908
    103 Digestive and Liver Disease Specialists Norfolk Virginia United States 23502
    104 Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond Richmond Virginia United States 23226
    105 Virginia Commonwealth University Health Clinical Research Services Unit Richmond Virginia United States 23298
    106 Virginia Mason Seattle Washington United States 98101
    107 Liver Institute Northwest Seattle Washington United States 98105
    108 Wlliam Osler Health System - Brampton Civic Hospital Brampton Canada L6R 3J7
    109 University of Calgary Liver Unit - Heritage Medical Research Clinic Calgary Canada T2N 4Z6
    110 McMaster University Medical Center Hamilton Canada L8N 3Z5
    111 Centre de Recherche du Centre Hospitalier de I'Universite de Montreal (CRCHUM) Montreal Canada H2X 0A9
    112 Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre (MUHC) Montreal Canada H4A 3J1
    113 Toronto General Hospital - University Health Network Toronto Canada M5G 2C4
    114 Toronto Liver Centre Toronto Canada M6H 3M1
    115 (G.I.R.I.) Gastrointestinal Research Institute Vancouver Canada V6Z 2K5
    116 Toronto Digestive Disease Associates Specialty Research Vanghan Canada L4L 4Y7
    117 CHU Amiens Picardie Amiens France 80054
    118 Centre Hosptitalier Universitaire d'Angers Angers France 49033
    119 Centre Hospitalier Regional Universitaire de Tours - Hopital Trousseau Chambray-les-Tours France 37170
    120 Hopital Henri Mondor Creteil France 94010
    121 CHU de Grenoble Grenoble Cedex 9 France 38043
    122 Hopital Claude Huriez Lille Cedex France 59 037
    123 Centre Hospitalier Universitaire Limoges Limoges France 87042
    124 Hopital de la Croix-Rousse Lyon France 69004
    125 Hopital Saint Joseph Marseille France 13008
    126 Centre Hospitalier Universitarie de Montpellier - Hospital Saint-Eloi Montpellier France 34295
    127 Centre Hospitalier Universitaire de Nice - Hopital L'archet Nice France 06202
    128 Hopitaux de Paris - Hopital Cochin Paris France 75014
    129 Hopital Beaujon Pessac France 33600
    130 CHU Rennes Pontchaillou Rennes France 35000
    131 Hopital Rangueil Toulouse France 31300
    132 Hopital Brabois Adultes - CHU de Nancy Vandoeuvre les Nancy France 54500
    133 Fukui-ken Saiseikai Hospital Fukui Japan 918-8503
    134 Juntendo University Shizouka Hospital Izunokuni Japan 410-2295
    135 University Hospital, Kyoto Prefectural University of Medicine Kyoto Japan 602-8566
    136 Japanese Red Cross Masashino Hospital Musashino-city Japan 1808610
    137 Osaka City University Hospital Osaka Japan 5458586
    138 Saga University Hospital Saga-shi Japan 849-0937
    139 Sapporo-Kosei General Hospital Sapporo-shi Japan 060-0033
    140 Saiseikai Suita Hospital Suita Japan 564-0013
    141 Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital Tokyo Japan 105-8470
    142 Ehime University Hospital Toon-Shi Japan 791-0295
    143 Yamagata University Hospital Yamagata Japan 9909585
    144 Yokohama City University Hospital Yokohama-shi Japan 2360004
    145 Latin Clinical Trial Center San Juan Puerto Rico 00909
    146 FDI Clinical Research San Juan Puerto Rico 00927
    147 Hospital Germans Trias i Pujol Badalona Barcelona Spain 08916
    148 Hospital Universitario Torrecardenas Almeria Spain 04009
    149 Hospital del Mar Barcelona Spain 08003
    150 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    151 Hospital Clinic De Barcelona Barcelona Spain 8036
    152 Hospital General Universiatrio Gregorio Maranon Madrid Spain 28007
    153 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    154 Hospital Universitario La Paz Edificio de Malemidad Madrid Spain 28046
    155 Hospital Universitario Puerta de Hierro-Majadahonda Majadahonda Spain 28222
    156 Complejo Hospitalario de Pontevedra Pontevedra Spain 36071
    157 Hospital Universitario Virgin del Rocio Sevilla Spain 41013
    158 Consorcio Hospital General Universitario de Valencia Valencia Spain 46014
    159 Hospital Universitario y Politecnlo la Fe Valencia Spain 46026

    Sponsors and Collaborators

    • Gilead Sciences
    • Novo Nordisk A/S

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT04971785
    Other Study ID Numbers:
    • GS-US-454-6075
    • 2021-001445-12
    • jRCT2071210112
    First Posted:
    Jul 21, 2021
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Fatty Liver
    Non-alcoholic Fatty Liver Disease
    Firsocostat

    Study Results

    No Results Posted as of Aug 23, 2022