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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02943447
Recruitment Status : Terminated (The study was terminated because of the availability of alternate therapies for primary biliary cholangitis (PBC).)
First Posted : October 24, 2016
Results First Posted : January 13, 2020
Last Update Posted : September 22, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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

Condition or disease Intervention/treatment Phase
Primary Biliary Cholangitis Drug: Cilofexor Drug: Placebo to match cilofexor Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 1, 2016
Actual Primary Completion Date : September 4, 2019
Actual Study Completion Date : September 4, 2019


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 Name: 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 Name: 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 Name: GS-9674




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase [ Time Frame: First dose date up to Week 12 + 30 days ]
  2. Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase [ Time Frame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days ]
  3. Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase [ Time Frame: First dose date up to Week 12 + 30 days ]
    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.

  4. Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase [ Time Frame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02943447


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

Documents provided by Gilead Sciences:
Study Protocol  [PDF] February 9, 2017
Statistical Analysis Plan  [PDF] August 14, 2018

Publications of Results:
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.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02943447    
Other Study ID Numbers: GS-US-427-4024
2016-002443-42 ( EudraCT Number )
First Posted: October 24, 2016    Key Record Dates
Results First Posted: January 13, 2020
Last Update Posted: September 22, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangitis
Liver Cirrhosis, Biliary
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Cholestasis, Intrahepatic
Cholestasis