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

Nonalcoholic Steatohepatitis Clinical Trial

— WAYFIND  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04971785
• Other study ID #: GS-US-454-6075
• Secondary ID: 2021-001445-12jR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 9, 2021
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 457
• Est. completion date: December 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Semaglutide (SEMA)
Administered as subcutaneous (SC) injection
• Cilofexor (CILO)/Firsocostat (FIR)
Tablets administered orally
• PTM SEMA
Administered as SC injection
• PTM CILO/FIR
Tablets administered orally

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Eastern Health, Box Hill Hospital	Box Hill	Victoria
Australia	Monash Health, Monash Medical Centre (Clayton)	Clayton	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Canada	Wlliam Osler Health System - Brampton Civic Hospital	Brampton
Canada	University of Calgary Liver Unit - Heritage Medical Research Clinic	Calgary
Canada	McMaster University Medical Center	Hamilton
Canada	London Health Sciences Centre - University Hospital	London
Canada	Centre de Recherche du Centre Hospitalier de I'Universite de Montreal (CRCHUM)	Montreal
Canada	Chronic Viral Illness Service, Royal Victoria Hospital, McGill University Health Centre (MUHC)	Montreal
Canada	Toronto General Hospital - University Health Network	Toronto
Canada	Toronto Liver Centre	Toronto
Canada	(G.I.R.I.) Gastrointestinal Research Institute	Vancouver
Canada	Gordon and Leslie Diamond Health Care Centre, Vancouver General Hospital, UBC Division of Gastroenterology	Vancouver
Canada	Toronto Digestive Disease Associates Specialty Research	Vanghan
France	CHU Amiens Picardie	Amiens
France	Centre Hosptitalier Universitaire d'Angers	Angers
France	Centre Hospitalier Regional Universitaire de Tours - Hopital Trousseau	Chambray-les-Tours
France	Hopital Henri Mondor	Creteil
France	CHU de Grenoble	Grenoble Cedex 9
France	Hopital Claude Huriez	Lille Cedex
France	Centre Hospitalier Universitaire Limoges	Limoges
France	Hopital de la Croix-Rousse	Lyon
France	Hopital Saint Joseph	Marseille
France	Centre Hospitalier Universitarie de Montpellier - Hospital Saint-Eloi	Montpellier
France	Centre Hospitalier Universitaire de Nice - Hopital L'archet	Nice
France	Hopital Universitaire Pitie Salpetriere	Paris
France	Hopitaux de Paris - Hopital Cochin	Paris
France	Hopital Beaujon	Pessac
France	Hopital Haut Leveque	Pessac Cedex
France	CHU Rennes Pontchaillou	Rennes
France	Hopital Rangueil	Toulouse
France	Hopital Brabois Adultes - CHU de Nancy	Vandoeuvre les Nancy
Japan	Fukui-ken Saiseikai Hospital	Fukui
Japan	Juntendo University Shizouka Hospital	Izunokuni
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto
Japan	Japanese Red Cross Masashino Hospital	Musashino-city
Japan	Osaka City University Hospital	Osaka
Japan	Saga University Hospital	Saga-shi
Japan	Sapporo-Kosei General Hospital	Sapporo-shi
Japan	Saiseikai Suita Hospital	Suita
Japan	Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital	Tokyo
Japan	Ehime University Hospital	Toon-Shi
Japan	Yamagata University Hospital	Yamagata
Japan	Yokohama City University Hospital	Yokohama-shi
Puerto Rico	FDI Clinical Research	San Juan
Puerto Rico	Latin Clinical Trial Center	San Juan
Puerto Rico	VA Caribbean Healthcare System	San Juan
Spain	Hospital Universitario Torrecardenas	Almeria
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic De Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General Universiatrio Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz Edificio de Malemidad	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda
Spain	Complejo Hospitalario de Pontevedra	Pontevedra
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago De Compostella
Spain	Hospital Universitario Virgin del Rocio	Sevilla
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario y Politecnlo la Fe	Valencia
Spain	Hospital Clinico Universitario de Valladolid	Valladolid
United States	Center for Research at Southwest Gastroenterology Associates, PC	Albuquerque	New Mexico
United States	Michigan Medicine - University of Michigan	Ann Arbor	Michigan
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Asheville Gastroenterology, a Division of Digestive Health Partners, PA	Asheville	North Carolina
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Pinnacle Clinical Research	Austin	Texas
United States	Mercy Medical Center	Baltimore	Maryland
United States	GI Alliance	Baton Rouge	Louisiana
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of Alabama at Birmingham Hospital	Birmingham	Alabama
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Synergy Healthcare	Bradenton	Florida
United States	South Texas Research Institute	Brownsville	Texas
United States	The University Of Vermont Medical Center	Burlington	Vermont
United States	GI Alliance	Cedar Park	Texas
United States	Arizona Health Research	Chandler	Arizona
United States	The Institution For Liver Health dba Arizona Liver Health	Chandler	Arizona
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health Transplant and Center for Liver Disease	Charlotte	North Carolina
United States	Charlotte Gastroenterology & Hepatology, PLLC	Charlotte	North Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Wake Research - ClinsSearch, LLC	Chattanooga	Tennessee
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Rush University Medical Group - Department of Hepatology	Chicago	Illinois
United States	Iowa Digestive Disease Center, PC	Clive	Iowa
United States	Columbia Digestive Health Research	Columbia	South Carolina
United States	GI Associates Research	Columbia	Missouri
United States	Optimed Research	Columbus	Ohio
United States	Northeast GI Research Division	Concord	North Carolina
United States	Southern California Research Center	Coronado	California
United States	GI Alliance	Dallas	Texas
United States	Internal Medicine Digestive and Liver Diseases Clinical Trials	Dallas	Texas
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	Southeast Clinical Research LLC	Dalton	Georgia
United States	Soma Clinical Trials, LLC	Denison	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Digestive Health Specialists	Dothan	Alabama
United States	Velocity Clinical Research - Providence	East Greenwich	Rhode Island
United States	DHR Health Institute for Research and Development Cancer Research Center	Edinburg	Texas
United States	South Texas Research Institute	Edinburg	Texas
United States	South Denver Gastroenterology	Englewood	Colorado
United States	Coastal Research Institute	Fayetteville	North Carolina
United States	Digestive Disease Research	Florham Park	New Jersey
United States	GI Alliance	Flowood	Mississippi
United States	Southwest General Healthcare Center	Fort Myers	Florida
United States	GI Alliance	Fort Worth	Texas
United States	Greater Boston Gastroenterology	Framingham	Massachusetts
United States	Allied Health Clinical Research Organization, LLC	Freehold	New Jersey
United States	University of California, San Francisco - Fresno	Fresno	California
United States	University of Florida Hepatology Research at the Clinical and Translational Research Building	Gainesville	Florida
United States	GI Alliance	Garland	Texas
United States	Pinnacle Clinical Research	Georgetown	Texas
United States	Woodholme Gastroenterology Associates	Glen Burnie	Maryland
United States	Digestive Disease Research Center	Greenwood	South Carolina
United States	Velocity Clinical Research, Hallandale Beach	Hallandale Beach	Florida
United States	Texas Digestive Specialists	Harlingen	Texas
United States	Indago Research and Health Center, Inc.	Hialeah	Florida
United States	Maya Research Center	Hialeah	Florida
United States	New Generation of Medical Research	Hialeah	Florida
United States	Evolution Clinical Research, INC	Hialeah Gardens	Florida
United States	Sunbright Health Medical Center	Homestead	Florida
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Research Institute	Houston	Texas
United States	Liver Associates of Texas, P.A.	Houston	Texas
United States	Liver Specialists of Texas	Houston	Texas
United States	Indiana University Health Enterprise Clinical Research Operations	Indianapolis	Indiana
United States	Nature Coast Clinical Research	Inverness	Florida
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Southern Therapy and Advanced Research	Jackson	Mississippi
United States	Encore Borland-Groover Clinical Research	Jacksonville	Florida
United States	UF Health Jacksonville-Gastroenterology Emerson	Jacksonville	Florida
United States	Gastrointestinal Associates of Northeast Tennessee	Johnson City	Tennessee
United States	Kansas City Research Institute	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	BioStar Clinical Research Group Inc.	Katy	Texas
United States	University of California, San Diego - Altman Clinical and Translational Research Institute	La Jolla	California
United States	Combined Gastro Research, LLC	Lafayette	Louisiana
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Gastro Care Institute (Fibroscan)	Lancaster	California
United States	Sierra Clinical Research	Las Vegas	Nevada
United States	ARCare Center for Clinical Research	Little Rock	Arkansas
United States	Arkansas Diagnostic Center	Little Rock	Arkansas
United States	Digestive Health Research of Southern California	Long Beach	California
United States	Biopharma Informatic, LLC	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Keck Medical Center of USC Healthcare Consultation II	Los Angeles	California
United States	GI Alliance	Lubbock	Texas
United States	North Alabama Health Research, LLC	Madison	Alabama
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Northwell Health Center for Liver Diseases	Manhasset	New York
United States	Gastrointestinal (GI) Specialists of Georgia	Marietta	Georgia
United States	Tandem Clinical Research GI, LLC	Marrero	Louisiana
United States	Biopharma Informatic, LLC	McAllen	Texas
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Century Research, LLC	Miami	Florida
United States	G+C Research Group	Miami	Florida
United States	International Medical Investigational Centers, Inc.	Miami	Florida
United States	ProLive Medical Research, Corp	Miami	Florida
United States	Schiff Center for Liver Diseases/ University of Miami	Miami	Florida
United States	Ocean Blue Medical Research Center, Inc	Miami Springs	Florida
United States	Delta Research Partners	Monroe	Louisiana
United States	Lucas Research, Inc.	Morehead City	North Carolina
United States	Intermountain Medical Center	Murray	Utah
United States	United Medical Doctors	Murrieta	California
United States	Gastroenterology Group of Naples	Naples	Florida
United States	Quality Medical Research, PLLC	Nashville	Tennessee
United States	Gastroenterology Health Partners, PLLC	New Albany	Indiana
United States	Yale Center for Clinical Investigation, Church Street Research Unit	New Haven	Connecticut
United States	Oschner Clinic Foundation	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Advanced Research Institute, Inc.	New Port Richey	Florida
United States	Liver Clinic (study visits, Fibroscan): Columbia University Irving Medical Center / NewYork Presbyterian Hospital	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	New York University Langone Health	New York	New York
United States	The New York - Presbyterian Hospital	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Ocala GI Research	Ocala	Florida
United States	Knowledge Research Center	Orange	California
United States	Palmtree Clinical Research, Inc.	Palm Springs	California
United States	California Liver Research Institute	Pasadena	California
United States	Digestive System Healthcare	Pasadena	Texas
United States	The Institute for Liver Health DBA Arizona Liver Health	Peoria	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Advanced Medical Research Center	Port Orange	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Cadena Care Institute, LLC	Poway	California
United States	University Gastroenterology	Providence	Rhode Island
United States	Carolina's GI Research, LLC	Raleigh	North Carolina
United States	Stanford Medicine Outpatient Center	Redwood City	California
United States	Inland Empire Clinical Trials	Rialto	California
United States	Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	Virginia Commonwealth University Health Clinical Research Services Unit	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California, Davis Medical Center	Sacramento	California
United States	University of Utah Hospital	Salt Lake City	Utah
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas
United States	Diabetes and Glandular Disease Clinic, P.A.	San Antonio	Texas
United States	Pinnacle Clinical Research, LLC	San Antonio	Texas
United States	Medical Associates Research Group	San Diego	California
United States	Precision Research Institute	San Diego	California
United States	Research and Education Inc.	San Diego	California
United States	TriWest Research Associates, LLC	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	University of California, San Francisco - Liver Clinic	San Francisco	California
United States	San Jose Gastroenterology at One Health	San Jose	California
United States	GI Alliance (Patients Seen, IP Shipment & Fibroscan)	San Marcos	Texas
United States	Covenant Metabolic Specialists, LLC	Sarasota	Florida
United States	Liver Institute Northwest	Seattle	Washington
United States	Virginia Mason	Seattle	Washington
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Digestive Research Alliance of Michigan	South Bend	Indiana
United States	Hawthorn Medical Associates	South Dartmouth	Massachusetts
United States	Velocity Clinical Research, Spartanburg	Spartanburg	South Carolina
United States	DSI Research	Springboro	Ohio
United States	Gastrointestinal Alliance - Sun City	Sun City	Arizona
United States	Kansas Medical Clinic PA	Topeka	Kansas
United States	Adobe Clinical Research, LLC	Tucson	Arizona
United States	The Institution For Liver Health dba Arizona Liver Health	Tucson	Arizona
United States	Options Health Research, LLC	Tulsa	Oklahoma
United States	Impact Research Institute	Waco	Texas
United States	GI Alliance	Webster	Texas
United States	Velocity Clinical Research, Salt Lake City	West Jordan	Utah
United States	Clinical Research Institute of Ohio, LLC	Westlake	Ohio
United States	Digestive Health Research of North Texas	Wichita Falls	Texas
United States	Charter Research	Winter Park	Florida
United States	Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center	Wyoming	Michigan
United States	Huron Gastroenterology Associates	Ypsilanti	Michigan
United States	Florida Medical Clinic, LLC	Zephyrhills	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Japan,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Worsening of NASH is defined as a = 1-point increase in hepatocellular ballooning or lobular inflammation.	Week 72
Secondary	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	Worsening of NASH is defined as a = 1-point increase in hepatocellular ballooning or lobular inflammation.	Week 72
Secondary	Percentage of Participants With NASH Resolution in Participants Treated with SEMA+CILO/FIR Versus Placebo	NASH resolution is defined as lobular inflammation of 0 or 1 and hepatocellular ballooning of 0.	Week 72
Secondary	Percentage of Participants With NASH Resolution In Participants Treated With SEMA+CILO/FIR Versus CILO/FIR Alone		Week 72

External Links

•   Gilead Clinical Trials Website