Study of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (WAYFIND)
Nonalcoholic Steatohepatitis
About this trial
This is an interventional treatment trial for Nonalcoholic Steatohepatitis
Eligibility Criteria
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.
Sites / Locations
- University of Alabama at Birmingham Hospital
- Digestive Health Specialists
- North Alabama Health Research, LLC
- The Institution For Liver Health dba Arizona Liver Health
- Arizona Health Research
- The Institute for Liver Health DBA Arizona Liver Health
- Gastrointestinal Alliance - Sun City
- Adobe Clinical Research, LLC
- The Institution For Liver Health dba Arizona Liver Health
- Arkansas Diagnostic Center
- ARCare Center for Clinical Research
- Arkansas Gastroenterology
- Southern California Research Center
- University of California, San Francisco - Fresno
- University of California, San Diego - Altman Clinical and Translational Research Institute
- Gastro Care Institute (Fibroscan)
- Digestive Health Research of Southern California
- Kaiser Permanente Los Angeles Medical Center
- Keck Medical Center of USC Healthcare Consultation II
- Biopharma Informatic, LLC
- United Medical Doctors
- Knowledge Research Center
- Palmtree Clinical Research, Inc.
- California Liver Research Institute
- Cadena Care Institute, LLC
- Stanford Medicine Outpatient Center
- Inland Empire Clinical Trials
- University of California, Davis Medical Center
- Research and Education Inc.
- TriWest Research Associates, LLC
- Precision Research Institute
- Medical Associates Research Group
- Quest Clinical Research
- University of California, San Francisco - Liver Clinic
- San Jose Gastroenterology at One Health
- University of Colorado Anschutz Medical Campus
- South Denver Gastroenterology
- Yale Center for Clinical Investigation, Church Street Research Unit
- Excel Medical Clinical Trials, LLC
- Synergy Healthcare
- Southwest General Healthcare Center
- University of Florida Hepatology Research at the Clinical and Translational Research Building
- Velocity Clinical Research, Hallandale Beach
- Evolution Clinical Research, INC
- Indago Research and Health Center, Inc.
- Maya Research Center
- New Generation of Medical Research
- Sunbright Health Medical Center
- Nature Coast Clinical Research
- UF Health Jacksonville-Gastroenterology Emerson
- Encore Borland-Groover Clinical Research
- Florida Research Institute
- Ocean Blue Medical Research Center, Inc
- G+C Research Group
- Schiff Center for Liver Diseases/ University of Miami
- Advanced Pharma CR, LLC
- Century Research, LLC
- ProLive Medical Research, Corp
- International Medical Investigational Centers, Inc.
- Gastroenterology Group of Naples
- Advanced Research Institute, Inc.
- Ocala GI Research
- Advanced Medical Research Center
- Progressive Medical Research
- Covenant Metabolic Specialists, LLC
- Charter Research
- Florida Medical Clinic, LLC
- Southeast Clinical Research LLC
- Gastrointestinal (GI) Specialists of Georgia
- Rush University Medical Group - Department of Hepatology
- Indiana University Health Enterprise Clinical Research Operations
- Gastroenterology Health Partners, PLLC
- Digestive Research Alliance of Michigan
- Iowa Digestive Disease Center, PC
- University of Iowa Hospitals and Clinics
- University of Kansas Medical Center
- Kansas Medical Clinic PA
- GI Alliance
- Combined Gastro Research, LLC
- Tandem Clinical Research GI, LLC
- Delta Research Partners
- Tulane University Health Sciences Center
- Oschner Clinic Foundation
- Louisiana Research Center, LLC
- Mercy Medical Center
- Walter Reed National Military Medical Center
- Woodholme Gastroenterology Associates
- Beth Israel Deaconess Medical Center
- Greater Boston Gastroenterology
- Hawthorn Medical Associates
- Michigan Medicine - University of Michigan
- Clinical Research Institute of Michigan, LLC
- Henry Ford Health System
- Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center
- Huron Gastroenterology Associates
- Mayo Clinic
- GI Alliance
- Southern Therapy and Advanced Research
- Clinical Research Professionals
- GI Associates Research
- Kansas City Research Institute
- Sierra Clinical Research
- Digestive Disease Research
- Allied Health Clinical Research Organization, LLC
- Rutgers New Jersey Medical School
- Center for Research at Southwest Gastroenterology Associates, PC
- Northwell Health Center for Liver Diseases
- New York University Langone Health
- Mount Sinai Medical Center
- Liver Clinic (study visits, Fibroscan): Columbia University Irving Medical Center / NewYork Presbyterian Hospital
- The New York - Presbyterian Hospital
- University of Rochester Medical Center
- Asheville Gastroenterology, a Division of Digestive Health Partners, PA
- Atrium Health Transplant and Center for Liver Disease
- Charlotte Gastroenterology & Hepatology, PLLC
- Northeast GI Research Division
- Coastal Research Institute
- Lucas Research, Inc.
- Carolina's GI Research, LLC
- Optimed Research
- DSI Research
- Clinical Research Institute of Ohio, LLC
- Options Health Research, LLC
- University of Pittsburgh Medical Center
- Velocity Clinical Research - Providence
- University Gastroenterology
- Medical University of South Carolina
- Columbia Digestive Health Research
- Digestive Disease Research Center
- Velocity Clinical Research, Spartanburg
- Wake Research - ClinsSearch, LLC
- Gastrointestinal Associates of Northeast Tennessee
- Quality Medical Research, PLLC
- Texas Clinical Research Institute
- Pinnacle Clinical Research
- South Texas Research Institute
- GI Alliance
- The Liver Institute at Methodist Dallas Medical Center
- GI Alliance
- Internal Medicine Digestive and Liver Diseases Clinical Trials
- Soma Clinical Trials, LLC
- DHR Health Institute for Research and Development Cancer Research Center
- South Texas Research Institute
- GI Alliance
- GI Alliance
- Pinnacle Clinical Research
- Texas Digestive Specialists
- Houston Methodist Hospital
- Liver Associates of Texas, P.A.
- Liver Specialists of Texas
- Biopharma Informatic, LLC
- Houston Research Institute
- Biopharma Informatic, LLC
- BioStar Clinical Research Group Inc.
- GI Alliance
- Biopharma Informatic, LLC
- Digestive System Healthcare
- American Research Corporation at the Texas Liver Institute
- Diabetes and Glandular Disease Clinic, P.A.
- Pinnacle Clinical Research, LLC
- GI Alliance (Patients Seen, IP Shipment & Fibroscan)
- Impact Research Institute
- GI Alliance
- Digestive Health Research of North Texas
- Intermountain Medical Center
- University of Utah Hospital
- Velocity Clinical Research, Salt Lake City
- The University Of Vermont Medical Center
- University of Virginia Medical Center
- Manassas Clinical Research Center
- Digestive and Liver Disease Specialists
- Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
- Virginia Commonwealth University Health Clinical Research Services Unit
- Virginia Mason
- Liver Institute Northwest
- Liverpool Hospital
- Westmead Hospital
- Royal Brisbane and Women's Hospital
- Flinders Medical Centre
- Eastern Health, Box Hill Hospital
- Monash Health, Monash Medical Centre (Clayton)
- Royal Perth Hospital
- Wlliam Osler Health System - Brampton Civic Hospital
- University of Calgary Liver Unit - Heritage Medical Research Clinic
- McMaster University Medical Center
- London Health Sciences Centre - University Hospital
- Centre de Recherche du Centre Hospitalier de I'Universite de Montreal (CRCHUM)
- Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre (MUHC)
- Toronto General Hospital - University Health Network
- Toronto Liver Centre
- Gordon and Leslie Diamond Health Care Centre, Vancouver General Hospital, UBC Division of Gastroenterology
- (G.I.R.I.) Gastrointestinal Research Institute
- Toronto Digestive Disease Associates Specialty Research
- CHU Amiens Picardie
- Centre Hosptitalier Universitaire d'Angers
- Centre Hospitalier Regional Universitaire de Tours - Hopital Trousseau
- Hopital Henri Mondor
- CHU de Grenoble
- Hopital Claude Huriez
- Centre Hospitalier Universitaire Limoges
- Hopital de la Croix-Rousse
- Hopital Saint Joseph
- Centre Hospitalier Universitarie de Montpellier - Hospital Saint-Eloi
- Centre Hospitalier Universitaire de Nice - Hopital L'archet
- Hopital Universitaire Pitie Salpetriere
- Hopitaux de Paris - Hopital Cochin
- Hopital Haut Leveque
- Hopital Beaujon
- CHU Rennes Pontchaillou
- Hopital Rangueil
- Hopital Brabois Adultes - CHU de Nancy
- Fukui-ken Saiseikai Hospital
- Juntendo University Shizouka Hospital
- University Hospital, Kyoto Prefectural University of Medicine
- Japanese Red Cross Masashino Hospital
- Osaka City University Hospital
- Saga University Hospital
- Sapporo-Kosei General Hospital
- Saiseikai Suita Hospital
- Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital
- Ehime University Hospital
- Yamagata University Hospital
- Yokohama City University Hospital
- Latin Clinical Trial Center
- VA Caribbean Healthcare System
- FDI Clinical Research
- Hospital Germans Trias i Pujol
- Hospital Universitario Torrecardenas
- Hospital del Mar
- Hospital Universitari Vall d'Hebron
- Hospital Clinic De Barcelona
- Hospital General Universiatrio Gregorio Maranon
- Hospital Universitario Ramon y Cajal
- Hospital Universitario La Paz Edificio de Malemidad
- Hospital Universitario Puerta de Hierro-Majadahonda
- Complejo Hospitalario de Pontevedra
- Hospital Universitario Marques de Valdecilla
- Hospital Clinico Universitario de Santiago
- Hospital Universitario Virgin del Rocio
- Consorcio Hospital General Universitario de Valencia
- Hospital Universitario y Politecnlo la Fe
- Hospital Clinico Universitario de Valladolid
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Placebo Comparator
SEMA + CILO/FIR FDC
SEMA + Placebo-To-Match (PTM) CILO/FIR
PTM SEMA + CILO/FIR FDC
PTM SEMA + PTM CILO/FIR
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
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
PTM Semaglutide once weekly and CILO/FIR 30 mg/20 mg FDC administered once daily for 72 weeks
PTM Semaglutide once weekly and PTM CILO/FIR once daily for 72 weeks