Study of Cilofexor in Adults With Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis Clinical Trial

— PRIMIS  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03890120
• Other study ID #: GS-US-428-4194
• Secondary ID: 2019-000204-14jR
• Status: Terminated
• Phase: Phase 3
• Start date: March 27, 2019
• Est. completion date: December 23, 2022

Study information

• Verified date: November 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 419
• Est. completion date: December 23, 2022
• Est. primary completion date: November 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Cilofexor
100 mg tablet administered orally once daily
• Placebo
Tablet administered orally once daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Japan,  New Zealand,  Spain,  Switzerland,  United Kingdom, 

References & Publications (2)

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. — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Serum Concentrations of Alkaline Phosphatase (ALP) at Blinded Phase Week 96		Baseline, Blinded Phase Week 96
Secondary	Change From Baseline in Serum Concentrations of Alanine Aminotransferase (ALT) at Blinded Phase Week 96		Baseline, Blinded Phase Week 96
Secondary	Change From Baseline in Serum Concentrations of Fasting Total Bile Acids at Blinded Phase Week 96		Baseline, Blinded Phase Week 96
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Gilead Clinical Trials Website