Study of Cilofexor in Adults With Primary Sclerosing Cholangitis (PRIMIS)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Subjects With Primary Sclerosing Cholangitis

The primary objective of this study is to evaluate whether cilofexor reduces the risk of fibrosis progression among non-cirrhotic adults with primary sclerosing cholangitis (PSC).

Study Overview

• Status: Terminated
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Cilofexor; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 419
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital Sydney
    • Penrith, New South Wales, Australia, 2751
      • Nepean Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Coral Sea Clinical Research Institute - Mackay
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women'S Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Ltd
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Austria
  • Klagenfurt am Wörthersee, Austria, 9020
    • Landeskrankenanstalten-Betriebsgesellscaft - KABEG, Klinikum Klagenfurt am Wörthersee
  • Vienna, Austria, 1090
    • Allgemeines Krankenhaus Wien
• Belgium
  • Bruxelles, Belgium, 10070
    • Hôpital Erasme - ULB
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Ghent, Belgium, 9000
    • Algemeen ziekenhuis Maria Middelares
  • Leuven, Belgium, B-3000
    • Universitair Ziekenhuis Leuven
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège Site Sart Tilman
• Canada
  • Brampton, Canada, L6R 3J7
    • William Osler Health System - Brampton Civic Hospital
  • Calgary, Canada, T2N 4Z6
    • University of Calgary Liver Unit - Heritage Medical Research Clinic (HMRC)
  • Edmonton, Canada, T6G 2X8
    • University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre (WMC)
  • Halifax, Canada, B3L 1E4
    • Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority
  • Hamilton, Canada, L8N 4A6
    • St. Joseph's Healthcare Hamilton
  • Hamilton, Canada, L8S 4L8
    • McMaster University Medical Center
  • Montreal, Canada, H2X 3J4
    • Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)
  • Montreal, Canada, H4A 3J1
    • Chronic Viral Illness Service/McGill University Health Centre (MUHC)
  • Toronto, Canada, M6H 3M1
    • Toronto Liver Centre
  • Toronto, Canada, M5G 2C4
    • Toronto General Hospital - Toronto Centre for Liver Disease (TCLD)
  • Vancouver, Canada, V5Z 1M9
    • Gordon and Leslie Diamond Health Care Centre, Vancouver General Hospital, UBC Division of Gastroenterology
  • Vancouver, Canada, V6Z 2K5
    • (G.I.R.I.) GI Research Institute
  • Winnipeg, Canada, R3E 3P4
    • University of Manitoba/Health Sciences Centre
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • København Ø, Denmark, DK-2100
    • Copenhagen University Hospital - Hvidovre
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Hospital, Endoscopy Unit, Gastroenterology Outpatient clinic, Meilahden tomisairaala
  • Turku, Finland, 20520
    • Turku University Hospital, Gastroenterology Outpatient Clinic
• France
  • Amiens, France, 80054
    • CHU Amiens-Picardie Hôpital Sud
  • CHRU Lille, France, 59000
    • Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
  • Creteil, France, 94010
    • Hôpital Henri Mondor
  • Grenoble cedex 09, France, 38043
    • CHU Grenoble Alpes
  • Marseille, France, 13008
    • Hôpital Saint-Joseph
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Pessac, France, 33604
    • CHU Bordeaux-Hopital Haut-Leveque
  • Reims, France, 4025
    • Hopital Robert Debré - Centre Hospitalier Universitaire de Reims
  • Strasbourg, France, 67091
    • CHU de Strasbourg - Nouvel Hopital Civil
  • Toulouse, France, 31300
    • CHU de Toulouse - Hôpital Rangueil
  • Toulouse cedex, France, 31059
    • CHU de Toulouse Hopital Ranguiel
  • Villejuif, France, 94800
    • Hopital Paul Brousse
  • Herault
    • Montpellier cedex 5, Herault, France, 34295
      • Hôpital Saint-Eloi
• Germany
  • Berlin, Germany, 10825
    • GASTRO-Studien GbR
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Frankfurt am Main, Germany, 60590
    • Universitatsklinikum Frankfurt
  • Hannover, Germany, 30625
    • Medizinische Hochscule Hannover
  • Heidelberg, Germany, 69120
    • Universitätsklinik Heidelberg
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Gastroenterologie und Hepatologie
  • Kiel, Germany, 24146
    • Gastroenterologisch-Hepatologisches Zentrum Kiel
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig AOR
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Mannheim, Germany, 68167
    • Universitätsmedizin Mannheim, II. Medizinische Klinik
• Israel
  • Afula, Israel, 1834111
    • Emek Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Haifa, Israel
    • Carmel Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital Ein Kerem
  • Jerusalem, Israel, 64239
    • Shaare Zedek Medical Center
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 5265601
    • The Chaim Sheba Medical Center
  • Tel-Aviv, Israel, 62431
    • Tel Aviv Sourasky Medical Center
• Italy
  • Ancona, Italy, 60126
    • Dipartimento Gastroenterologico e dei Trapianti
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Moderna, Ospedale di Baggiovara
  • Milan, Italy, 20122
    • Ca'Granda Ospedale Maggiore Policlinico UOC Gastroenterologia ed Epatologia
  • Novara, Italy, 28100
    • Medicina Interna 1
  • Padova, Italy, 35128
    • Azienda Ospedale Universita Padova
  • Palermo, Italy, 90127
    • Azienda Ospedaliera Universitaria Policlinico P. Giaccone
  • Pisa, Italy, 56124
    • Azienda Ospedaliero-Universitaria Pisana - Unità Operativa Epatologia
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Rozzano, Italy, 20089
    • U.O.C. Gatroenterologia
  • Rozzano (Milan), Italy, 20089
    • Istituto Clinico Humanitas - Unita Operativa di Epatologia
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • IRCCS Ospedale Sollievo della Sofferenza
• Japan
  • Chiba-shi, Japan, 260-8670
    • Chiba University Hospital
  • Hiroshima, Japan, 7348551
    • Hiroshima University Hospital
  • Nagasaki, Japan, 856-8562
    • National Hospital Organization Nagasaki Medical Center
  • Okayama-shi, Japan, 7008558
    • Okayama University Hospital
  • Sendai, Japan, 980-8574
    • National University Corporation Tohoku University Tohoku University Hospital
  • Suita, Japan, 565-0871
    • Osaka University Hospital
  • Tokyo, Japan, 173-8606
    • Teikyo University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Toon-Shi, Japan, 791-0295
    • Ehime University Hospital
  • Yamagata, Japan, 9909585
    • Yamagata University Hospital
• New Zealand
  • Auckland, New Zealand, 92103
    • Auckland City Hospital
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Hamilton, New Zealand, 2001
    • Waikato Hospital
• Spain
  • Alicante, Spain, 3010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Majadahonda, Spain, 28220
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Pontevedra, Spain, 36071
    • Complejo Hospitalario de Pontevedra
  • Santiago de Compostela, Spain, 15706
    • Hospital Clinico Universitario Santiago de Compostela
  • Valencia, Spain, 46010
    • Hospital General Universitario de Valencia
  • Valencia, Spain, 46026
    • Hospital Universitari Politecnic La Fe de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Switzerland
  • Bern, Switzerland, 3010
    • Universitätsspital Bern
  • Lugano, Switzerland, 6900
    • Epatocentro Ticino SA
  • Zurich, Switzerland, 8091
    • Universitatsspital Zurich
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • University Hospital Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Glasgow, United Kingdom, G4 0SF
    • NHS Greater Glasgow and Clyde
  • Leeds, United Kingdom
    • The Leeds Teaching Hospitals Nhs Trust
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospitals NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, E1 1BB
    • Barts Health Nhs Trust
  • London, United Kingdom, SW10 9NH
    • Chelsea And Westminster Hospital NHS Foundation Trust
  • London, United Kingdom, SE5 9NT
    • King's College Hospital NHS Foundation Trust
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals Nhs Trust
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Foundation Trust
  • Portsmouth, United Kingdom, PO6 3LY
    • Portsmouth Hospitals NHS Trust
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Institute for Liver Health
    • Phoenix, Arizona, United States, 85013
      • The Institute for Liver Heath
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • La Jolla, California, United States, 92037
      • Altman Clinical and Translational Research Institute (Clinic)
    • La Jolla, California, United States, 92037
      • Scripps Clinic/Green Hospital
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc.
    • Palo Alto, California, United States, 94025
      • Stanford hospital
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center (Study Visits)
    • San Francisco, California, United States, 94107
      • Sutter Pacific Medical Foundation - California Pacific Medical Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Liver Clinic
    • West Hollywood, California, United States, 90048
      • Cedars Sinai Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver and Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterology Associates
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, PC
  • Connecticut
    • New Haven, Connecticut, United States, 48109
      • Yale School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute, Inc
    • Port Orange, Florida, United States, 32127
      • Advanced Medical Research Center
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital; Clinical Research Unit
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center (outpatient clinic)
    • Evanston, Illinois, United States, 60201
      • NorthShore University Healthsystem
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health University Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Fall River, Massachusetts, United States, 02721
      • NECCR Primacare Research, LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine - University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Maplewood, Minnesota, United States, 55117
      • Minnesota Gastroenterology, PA
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39157
      • Southern Therapy and Advanced Research LLC
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University, Gastroenterology & Hepatology
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School - Doctors Office Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Manhasset, New York, United States, 11030
      • Northwell Health Center for Liver Diseases and Transplantation
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai Beth Israel
    • New York, New York, United States, 10032
      • Center for Liver Disease and Transplantation, Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of NC at Chapel Hill, Clinical and Translational Research Center (CTRC)
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Medical Center - Center for Liver Disease
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Holmes Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • South Carolina
    • Charleston, South Carolina, United States, 28204
      • Medical University of South Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center, LLP
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist University Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center - Digestive Disease Center
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Dallas, Texas, United States, 75203
      • The Liver Institute At Methodist Dallas Medical Center
    • Dallas, Texas, United States, 75246
      • Annette & Harold C. Simmons Transplant Institute @ Baylor University Medical Center at Dallas
    • Fort Worth, Texas, United States, 76104
      • Baylor Scott & White Medical Center at Fort Worth
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Advanced Liver Therapies
    • Humble, Texas, United States, 77338
      • Spring Gastroenterology Associates
    • San Antonio, Texas, United States, 78234
      • San Antonio Military Medical Center, Gastro/Hepatology
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center - Transplant Services
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
    • Fairfax, Virginia, United States, 22031
      • Verity Research Inc.
    • Richmond, Virginia, United States, 23226
      • Bon Secours Richmond Community Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Clinical Research Services Unit
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Diagnosis of large duct PSC
• Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0 - F3 fibrosis in the opinion of the central reader

• Individual has the following laboratory parameters at the screening visit, as determined by the central laboratory:

  • Platelet count ≥ 150,000/mm^3
  • Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
  • Alanine transaminase (ALT) ≤ 8 x upper limit of the normal range (ULN)
  • Total bilirubin < 2 mg/dL, unless the individual is known to have Gilbert's syndrome or hemolytic anemia
  • International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation
  • Negative anti-mitochondrial antibody

Key Exclusion Criteria:

• Current or prior history of any of the following:

  • Cirrhosis
  • Liver transplantation
  • Cholangiocarcinoma or hepatocellular carcinoma (HCC)
  • Ascending cholangitis within 30 days of screening
• Presence of a percutaneous drain or biliary stent
• Other causes of liver disease
• Current or prior history of unstable cardiovascular disease
• Current moderate to severe inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis)

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cilofexor 100 mg (Blinded Phase); Participants received cilofexor 100 mg tablet, orally, once daily for up to 100.3 weeks.	Drug: Cilofexor; 100 mg tablet administered orally once daily; Other Names: GS-9674
Placebo Comparator: Placebo (Blinded Phase); Participants received placebo to match cilofexor 100 mg tablet, orally, once daily for up to 98.1 weeks.	Drug: Placebo; Tablet administered orally once daily
Experimental: Cilofexor From Cilofexor 100 mg (OLE Phase); Participants who received cilofexor in blinded phase and had entered the open-label extension (OLE) phase received open-label cilofexor 100 mg tablet, orally, once daily for up to 44.7 weeks.	Drug: Cilofexor; 100 mg tablet administered orally once daily; Other Names: GS-9674
Experimental: Cilofexor From Placebo (OLE Phase); Participants who received placebo in blinded phase and had entered the OLE phase received open-label cilofexor 100 mg tablet, orally, once daily for up to 45.0 weeks.	Drug: Cilofexor; 100 mg tablet administered orally once daily; Other Names: GS-9674

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96	Progression of liver fibrosis was defined as having a ≥ 1-stage increase from baseline in fibrosis according to the Ludwig classification at Blinded Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).	Blinded Phase Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase	An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. For Blinded Study Phase and OLE Phase, TEAEs were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug.	First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Percentage of Participants Who Experienced TEAEs in The OLE Phase	An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. For Blinded Study Phase and OLE Phase, TEAEs were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug.	First dose date in the OLE Phase up to 45 weeks plus 30 days
Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase	An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.	First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase	An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.	First dose date in the OLE Phase up to 45 weeks plus 30 days
Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96		Baseline, Blinded Phase Week 96
Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96		Baseline, Blinded Phase Week 96
Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96		Baseline, Blinded Phase Week 96
Percentage of Participants With ≥ 25% Relative Reduction in Serum ALP Concentration From Baseline and No Worsening of Fibrosis According to the Ludwig Classification at Blinded Phase Week 96	The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).The percentage of participants with ≥ 25% reduction in serum ALP Concentration from baseline and no increase in fibrosis according to the Ludwig Classification at Blinded Phase Week 96 was analyzed.	Baseline, Blinded Phase Week 96
Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96	Fibrosis improvement was defined as having ≥ 1-stage decrease from baseline in fibrosis according to the Ludwig classification score at Blinded Study Phase Week 96. The stages of fibrosis was assessed according to Ludwig classification. Ludwig classification fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=no fibrosis, 4=cirrhosis).	Blinded Phase Week 96
Change From Baseline in Primary Sclerosing Cholangitis (PSC) Symptoms - Module 1 Based on Disease-specific Patient Reported Outcome (PSC-PRO) at Blinded Phase Week 96	The PSC-PRO addressed the severity of common everyday symptoms of PSC (eg, pruritus, fatigue, and right upper quadrant abdominal discomfort); and their functional impact (eg, on physical function, activities of daily living, and work productivity, etc). PSC-PRO module 1 - PSC symptoms contains a total of 12 questions asking about the severity of specific PSC symptoms on a scale of 0 (no symptoms) to 10 (symptoms as bad as you could imagine) with a 24-hour recall period. The total score, which is computed as 12 times the average of nonmissing scores of the 12 questions, can potentially range between 0 and 120, with higher scores indicating more severe symptoms. A positive change from baseline indicates worsening of symptoms.	Baseline, Blinded Phase Week 96
Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96	The Enhanced Liver Fibrosis (ELF™) test is a composite of three serum biomarkers of hepatobiliary fibrosis: hyaluronic acid, procollagen III amino-terminal peptide, and tissue inhibitor of metalloproteinase. A typical range for ELF™ test scores in PSC is between 6 and 14. Higher ELF™ test scores are associated with more severe liver disease. A positive change from baseline indicated worsening of fibrosis.	Baseline, Blinded Phase Week 96
Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96	Change in liver stiffness was measured by FibroScan® scores. FibroScan measures liver scarring by measuring the stiffness of the liver. It's normally between 2 and 6 kPa. Many people with liver disease(s) have a result that's higher than the normal range. Higher scores indicate increased scarring of the liver. A positive change from baseline indicates severe liver disease(s).	Baseline, Blinded Phase Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Trauner M, Chung C, Sterling K, Liu X, Lu X, Xu J, Tempany-Afdhal C, Goodman ZD, Farkkila M, Tanaka A, Trivedi P, Kowdley KV, Bowlus CL, Levy C, Myers RP. PRIMIS: design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis. BMC Gastroenterol. 2023 Mar 15;23(1):75. doi: 10.1186/s12876-023-02653-2.
• Trauner M, Levy C, Tanaka A, Goodman Z, Thorburn D, et al. A Phase 3 Randomized, Double-blind, Placebo-controlled Study Evaluation the Efficacy and Safety of Cilofexor in Patients With Non-cirrhotic Patients With Primary Sclerosing Cholangitis. J Hepatol. 2023 June;78(S1):S12-S13.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2019
• Primary Completion (Actual): November 10, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: GS-US-428-4194; 2019-000204-14 (EudraCT Number); jRCT2080224728 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No