Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis

Primary Sclerosing Cholangitis Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blind, Placebo Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Sclerosing Cholangitis Without Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02943460
• Other study ID #: GS-US-428-4025
• Secondary ID: 2016-002442-23
• Status: Completed
• Phase: Phase 2
• Start date: November 29, 2016
• Est. completion date: May 18, 2020

Study information

• Verified date: May 2021
• 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 the safety and tolerability of cilofexor in adults with primary sclerosing cholangitis (PSC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: May 18, 2020
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key Inclusion Criteria:

• Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous transhepatic cholangiogram (PTC)) within the previous 12 months
• Serum alkaline phosphatase (ALP) > 1.67 x upper limit of the normal range (ULN)
• For individuals on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable for at least 12 months prior to screening through the end of treatment. For individuals not on UDCA, no UDCA use for at least 12 months before screening through the end of treatment
• For individuals being administered biologic treatments (eg, antitumor necrosis factor (TNF) or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids, the dose must have been stable at least 3 months prior to screening and anticipated to remain stable throughout the trial
• Screening FibroSURE/FibroTest® <0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of total bilirubin.

Key Exclusion Criteria:

• Alanine aminotransferase (ALT) > 10 x ULN
• Total bilirubin > 2 x ULN
• International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
• Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography)
• Other causes of liver disease including secondary sclerosing cholangitis and viral, metabolic, alcoholic, and other autoimmune conditions. Individuals with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy;
• Ascending cholangitis within 60 days of screening
• Presence of a percutaneous drain or bile duct stent
• Use of fibrates or obeticholic acid within 3 months prior to screening through the end of treatment
• Cirrhosis of the liver as defined by any of the following:
• Historical liver biopsy demonstrating cirrhosis (eg, Ludwig stage 4 or Ishak stage = 5)
• Prior history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
• Liver stiffness > 14.4 kilopascal (kPa) by FibroScan
• Current, active inflammatory bowel disease (IBD) defined as a partial Mayo score of > 1 and/or a score on the Rectal Bleeding domain > 0. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Cilofexor
Tablet(s) administered orally once daily with food
• Placebo to match cilofexor
Tablet(s) administered orally once daily with food

Locations

Country	Name	City	State
Austria	Universitätsklinik Klinik für Innere Medizin III	Vienna
Canada	University of Calgary Liver Unit (Heritage Medical Research Clinic)	Calgary	Alberta
Canada	Toronto Liver Centre	Toronto	Ontario
United Kingdom	New Queen Elizabeth Hospital NHS Foundation Trust	Birmingham
United Kingdom	King's College Hospital NHS Foundation Trust	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United States	University of Colorado Denver	Aurora	Colorado
United States	University of Virginia	Charlottesville	Virginia
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Indiana University Health University Hospital	Indianapolis	Indiana
United States	Florida Digestive Health Specialists	Lakewood Ranch	Florida
United States	Schiff Center for Liver Diseases/University of Miami	Miami	Florida
United States	Intermountain Medical Center - Transplant Services	Murray	Utah
United States	Bon Secours St. Mary's Hospital of Richmond, Inc.	Richmond	Virginia
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California, Davis Medical Center	Sacramento	California
United States	Minnesota Gastroenterology, P.A.	Saint Paul	Minnesota
United States	University of California San Francisco	San Francisco	California
United States	Swedish Organ Transplant and Liver Center	Seattle	Washington
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  Canada,  United Kingdom, 

References & Publications (1)

Trauner M, Gulamhusein A, Hameed B, Caldwell S, Shiffman ML, Landis C, Eksteen B, Agarwal K, Muir A, Rushbrook S, Lu X, Xu J, Chuang JC, Billin AN, Li G, Chung C, Subramanian GM, Myers RP, Bowlus CL, Kowdley KV. The Nonsteroidal Farnesoid X Receptor Agoni — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase	Treatment-emergent adverse events occurring during the Blinded Phase were defined as 1 or both of the following: 1) Any adverse events (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 in the Blinded Phase (and before the first dosing date in the Open Label Extension (OLE) Phase), or 2) Any AEs leading to premature discontinuation of study drug in the Blinded Phase.	First dose date up to last dose date plus 30 days (Up to 17 weeks)
Primary	Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase	A serious adverse event was defined as an event that, at any dose, resulted in any of the following: death, life-threatening, 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 up to last dose date plus 30 days (Up to 17 weeks)
Primary	Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase	Treatment-emergent laboratory abnormalities occurring during the Blinded Phase were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug in the Blinded Phase plus 30 days (and prior to or on the first dose date of the OLE phase). The Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 was used for assigning toxicity grades (0 to 4, with higher grades indicating more severity).	First dose date up to last dose date plus 30 days (Up to 17 weeks)