Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Biliary Cholangitis Without Cirrhosis (PBC-Phase 2)

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

The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary biliary cholangitis (PBC).

Study Overview

• Status: Terminated
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Cilofexor; Drug: Placebo to match cilofexor

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Steiermark
    • Graz, Steiermark, Austria, 8036
  • Vienna
    • Wien, Vienna, Austria, 1090
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
    • Vancouver, British Columbia, Canada, V6Z 2K5
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0T6
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
    • Vaughan, Ontario, Canada, L4L 4Y7
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B215 2GW
    • London, England, United Kingdom, NW3 2QG
    • London, England, United Kingdom, SE5 9RS
    • Norwich, England, United Kingdom, NR4 7UY
• United States
  • California
    • Sacramento, California, United States, 95817
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Florida
    • Lakewood Ranch, Florida, United States, 34211
    • Miami, Florida, United States, 33136
  • Georgia
    • Marietta, Georgia, United States, 30060
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
  • Texas
    • Arlington, Texas, United States, 76012
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75203
    • Houston, Texas, United States, 77030
  • Virginia
    • Charlottesville, Virginia, United States, 22908
    • Newport News, Virginia, United States, 23602
  • Washington
    • Seattle, Washington, United States, 98104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Meets all of the following conditions

  • Definite or probable PBC as defined by at least 2 of the 3 following criteria:

    • Serum alkaline phosphatase (ALP) > the upper limit of normal (ULN)
    • Presence of anti-mitochondrial antibodies (AMA) in serum (≥ 1:40 on immunofluorescence)
    • Liver histological findings consistent with PBC including nonsuppurative, destructive cholangitis affecting mainly the interlobular bile and septal bile ducts
  • Serum ALP > 1.67 x ULN and/or total bilirubin >ULN but ≤ 2 x ULN
  • Ursodeoxycholic acid (UDCA) use at a stable dose for at least 12 months or intolerant of UDCA with no UDCA use for at least 12 months before screening
• 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) > 5 x ULN
• Total bilirubin > 2 x ULN
• International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
• Other causes of liver disease including viral, metabolic, alcoholic, and other autoimmune conditions. Participants 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.
• 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)
  • History of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
  • Liver stiffness > 16.9 kPa by FibroScan®

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 30 mg (Blinded Study Phase); Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.	Drug: Cilofexor; Tablet(s) administered orally once daily, with food; Other Names: GS-9674; Drug: Placebo to match cilofexor; Tablet(s) administered orally once daily, with food
Experimental: Cilofexor 100 mg (Blinded Study Phase); Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.	Drug: Cilofexor; Tablet(s) administered orally once daily, with food; Other Names: GS-9674; Drug: Placebo to match cilofexor; Tablet(s) administered orally once daily, with food
Placebo Comparator: Placebo (Blinded Study Phase); Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.	Drug: Placebo to match cilofexor; Tablet(s) administered orally once daily, with food
Experimental: Cilofexor (Open Label Extension Phase); Following the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks.	Drug: Cilofexor; Tablet(s) administered orally once daily, with food; Other Names: GS-9674

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase		First dose date up to Week 12 + 30 days
Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase		First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.	First dose date up to Week 12 + 30 days
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.	First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Kowdley KV, Minuk GY, Pagadala MR, Gulamhusein A, Swain MG, Neff GW, et al. The Nonsteroidal Farnesoid X Receptor (FXR) Agonist Cilofexor Improves Liver Biochemistry in Patients with Primary Biliary Cholangitis (PBC): A Phase 2, Randomized, Placebo-Controlled Trial [Abstract 45]. Hepatology AASLD Abstracts 2019;70 (Suppl 1):31A-2A.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): September 4, 2019
• Study Completion (Actual): September 4, 2019

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): September 22, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: GS-US-427-4024; 2016-002443-42 (EudraCT Number)

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