Clinical trial NCT03890120: Study of Cilofexor in Adults With Primary Sclerosing Cholangitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-03-26
Enrollment: 419
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Progression of Liver Fibrosis at Blinded Phase Week 96
timeFrame: Blinded Phase Week 96
Secondary outcomes:
measure: Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) in The Blinded Phase
timeFrame: First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
measure: Percentage of Participants Who Experienced TEAEs in The OLE Phase
timeFrame: First dose date in the OLE Phase up to 45 weeks plus 30 days
measure: Percentage of Participants Who Experienced Treatment-emergent Serious Adverse Events (SAEs) in the Blinded Phase
timeFrame: First dose date in the Blinded Phase up to 100.3 weeks plus 30 days
measure: Percentage of Participants Who Experienced Treatment-emergent SAEs in the OLE Phase
timeFrame: First dose date in the OLE Phase up to 45 weeks plus 30 days
measure: Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96
timeFrame: Baseline, Blinded Phase Week 96
measure: Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96
timeFrame: Baseline, Blinded Phase Week 96
measure: Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96
timeFrame: Baseline, Blinded Phase Week 96
measure: 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
timeFrame: Baseline, Blinded Phase Week 96
measure: Percentage of Participants With Fibrosis Improvement According to the Ludwig Classification at Blinded Phase Week 96
timeFrame: Blinded Phase Week 96
measure: 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
timeFrame: Baseline, Blinded Phase Week 96
measure: Change From Baseline in Enhanced Liver Fibrosis (ELF™ ) Test Score at Blinded Phase Week 96
timeFrame: Baseline, Blinded Phase Week 96
measure: Change From Baseline in Liver Stiffness by FibroScan® at Blinded Phase Week 96
timeFrame: Baseline, Blinded Phase Week 96
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Institute For Liver Health
state: Arizona
city: Phoenix
country: United States
facility: The Institute for Liver Heath
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: La Jolla
country: United States
facility: Altman Clinical and Translational Research Institute (Clinic)
state: California
city: La Jolla
country: United States
facility: Scripps Clinic/Green Hospital
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group Inc.
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center (study visits)
state: California
city: San Francisco
country: United States
facility: Sutter Pacific Medical Foundation - California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Liver Clinic
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver and Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology, PC
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute, Inc
state: Florida
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital; Clinical Research Unit
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center (outpatient clinic)
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Healthsystem
state: Illinois
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Fall River
country: United States
facility: NECCR PrimaCare Research, LLC
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine - University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Maplewood
country: United States
facility: Minnesota Gastroenterology, PA
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research LLC
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University, Gastroenterology & Hepatology
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: Rutgers New Jersey Medical School - Doctors Office Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health Center for Liver Diseases and Transplantation
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Center for Liver Disease and Transplantation, Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: The University of NC at Chapel Hill, Clinical and Translational Research Center (CTRC)
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center - Center for Liver Disease
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: Holmes Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Medical Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLP
state: South Dakota
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Digestive Disease Center
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: Annette & Harold C. Simmons Transplant Institute @ Baylor University Medical Center at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott & White Medical Center at Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Advanced Liver Therapies
state: Texas
city: Humble
country: United States
facility: Spring Gastroenterology Associates
state: Texas
city: San Antonio
country: United States
facility: San Antonio Military Medical Center, Gastro/Hepatology
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center - Transplant Services
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Fairfax
country: United States
facility: Verity Research Inc.
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Clinical Research Services Unit
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital Sydney
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Coral Sea Clinical Research Institute - Mackay
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Klagenfurt am Wörthersee
country: Austria
facility: Landeskrankenanstalten-Betriebsgesellscaft - KABEG, Klinikum Klagenfurt am Wörthersee
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus Wien
city: Bruxelles
country: Belgium
facility: Hôpital Erasme - ULB
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Ghent
country: Belgium
facility: Algemeen Ziekenhuis Maria Middelares
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liège Site Sart Tilman
city: Brampton
country: Canada
facility: William Osler Health System - Brampton Civic Hospital
city: Calgary
country: Canada
facility: University of Calgary Liver Unit - Heritage Medical Research Clinic (HMRC)
city: Edmonton
country: Canada
facility: University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre (WMC)
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
city: Hamilton
country: Canada
facility: McMaster University Medical Center
city: Montreal
country: Canada
facility: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)
city: Montreal
country: Canada
facility: Chronic Viral Illness Service/McGill University Health Centre (MUHC)
city: Toronto
country: Canada
facility: Toronto General Hospital - Toronto Centre for Liver Disease (TCLD)
city: Toronto
country: Canada
facility: Toronto Liver Centre
city: Vancouver
country: Canada
facility: Gordon and Leslie Diamond Health Care Centre, Vancouver General Hospital, UBC Division of Gastroenterology
city: Vancouver
country: Canada
facility: (G.I.R.I.) GI Research Institute
city: Winnipeg
country: Canada
facility: University of Manitoba/Health Sciences Centre
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: København Ø
country: Denmark
facility: Copenhagen University Hospital - Hvidovre
city: Helsinki
country: Finland
facility: Helsinki University Hospital, Endoscopy Unit, Gastroenterology Outpatient clinic, Meilahden tomisairaala
city: Turku
country: Finland
facility: Turku University Hospital, Gastroenterology Outpatient Clinic
city: Montpellier cedex 5
country: France
facility: Hôpital Saint-Eloi
state: Herault
city: Amiens
country: France
facility: CHU Amiens-Picardie Hôpital Sud
city: CHRU Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: Grenoble cedex 09
country: France
facility: CHU Grenoble Alpes
city: Marseille
country: France
facility: Hôpital Saint-Joseph
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pessac
country: France
facility: CHU Bordeaux-Hopital Haut-Leveque
city: Reims
country: France
facility: Hopital Robert Debré - Centre Hospitalier Universitaire de Reims
city: Strasbourg
country: France
facility: CHU de Strasbourg - Nouvel Hôpital Civil
city: Toulouse cedex
country: France
facility: CHU de Toulouse Hopital Ranguiel
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Rangueil
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Berlin
country: Germany
facility: GASTRO-Studien GbR
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Hannover
country: Germany
facility: Medizinische Hochscule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinik Heidelberg
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Gastroenterologie und Hepatologie
city: Kiel
country: Germany
facility: Gastroenterologisch-Hepatologisches Zentrum Kiel
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim, II. Medizinische Klinik
city: Afula
country: Israel
facility: Emek Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Sollievo della Sofferenza
state: Foggia
city: Ancona
country: Italy
facility: Dipartimento Gastroenterologico e dei Trapianti
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Moderna, Ospedale di Baggiovara
city: Milan
country: Italy
facility: Ca'Granda Ospedale Maggiore Policlinico UOC Gastroenterologia ed Epatologia
city: Novara
country: Italy
facility: Medicina Interna 1
city: Padova
country: Italy
facility: Azienda Ospedale Universita Padova
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico P. Giaccone
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana - Unità Operativa Epatologia
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Rozzano (Milan)
country: Italy
facility: Istituto Clinico Humanitas - Unita Operativa di Epatologia
city: Rozzano
country: Italy
facility: U.O.C. Gatroenterologia
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Nagasaki
country: Japan
facility: National Hospital Organization Nagasaki Medical Center
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
city: Sendai
country: Japan
facility: National University Corporation Tohoku University Tohoku University Hospital
city: Suita
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Teikyo University Hospital
city: Toon-Shi
country: Japan
facility: Ehime University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago de Compostela
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari Politecnic La Fe de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Bern
country: Switzerland
facility: Universitatsspital Bern
city: Lugano
country: Switzerland
facility: Epatocentro Ticino SA
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Aintree University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.