Back to resultsStudy to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
Primary Purpose
Primary Sclerosing Cholangitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cilofexor
Placebo to match cilofexor
Sponsored by
About this trial
This is an interventional treatment trial for Primary Sclerosing Cholangitis
Eligibility Criteria
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.
Sites / Locations
- University of California, Davis Medical Center
- University of California San Francisco
- University of Colorado Denver
- Florida Digestive Health Specialists
- Schiff Center for Liver Diseases/University of Miami
- Indiana University Health University Hospital
- Minnesota Gastroenterology, P.A.
- Duke University Medical Center
- The Liver Institute at Methodist Dallas Medical Center
- Intermountain Medical Center - Transplant Services
- University of Virginia
- Bon Secours St. Mary's Hospital of Richmond, Inc.
- McGuire VA Medical Center
- Virginia Commonwealth University
- Swedish Organ Transplant and Liver Center
- University of Washington
- Universitätsklinik Klinik für Innere Medizin III
- University of Calgary Liver Unit (Heritage Medical Research Clinic)
- Toronto Liver Centre
- New Queen Elizabeth Hospital NHS Foundation Trust
- Royal Free Hospital
- King's College Hospital NHS Foundation Trust
- Norfolk and Norwich University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
Cilofexor 100 mg (Blinded Study Phase)
Cilofexor 30 mg (Blinded Study Phase)
Placebo (Blinded Study Phase)
Cilofexor (Open Label Extension Phase)
Arm Description
Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks
Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks
Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks
Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks.
Outcomes
Primary Outcome Measures
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.
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.
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).
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02943460
Brief Title
Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
November 29, 2016 (Actual)
Primary Completion Date
February 28, 2018 (Actual)
Study Completion Date
May 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary sclerosing cholangitis (PSC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cilofexor 100 mg (Blinded Study Phase)
Arm Type
Experimental
Arm Description
Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks
Arm Title
Cilofexor 30 mg (Blinded Study Phase)
Arm Type
Experimental
Arm Description
Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks
Arm Title
Placebo (Blinded Study Phase)
Arm Type
Placebo Comparator
Arm Description
Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks
Arm Title
Cilofexor (Open Label Extension Phase)
Arm Type
Experimental
Arm Description
Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks.
Intervention Type
Drug
Intervention Name(s)
Cilofexor
Other Intervention Name(s)
GS-9674
Intervention Description
Tablet(s) administered orally once daily with food
Intervention Type
Drug
Intervention Name(s)
Placebo to match cilofexor
Intervention Description
Tablet(s) administered orally once daily with food
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase
Description
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.
Time Frame
First dose date up to last dose date plus 30 days (Up to 17 weeks)
Title
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase
Description
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.
Time Frame
First dose date up to last dose date plus 30 days (Up to 17 weeks)
Title
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase
Description
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).
Time Frame
First dose date up to last dose date plus 30 days (Up to 17 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Florida Digestive Health Specialists
City
Lakewood Ranch
State/Province
Florida
ZIP/Postal Code
34211
Country
United States
Facility Name
Schiff Center for Liver Diseases/University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Indiana University Health University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Minnesota Gastroenterology, P.A.
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55117
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
The Liver Institute at Methodist Dallas Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
Intermountain Medical Center - Transplant Services
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Bon Secours St. Mary's Hospital of Richmond, Inc.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Swedish Organ Transplant and Liver Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Universitätsklinik Klinik für Innere Medizin III
City
Vienna
Country
Austria
Facility Name
University of Calgary Liver Unit (Heritage Medical Research Clinic)
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Toronto Liver Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
Facility Name
New Queen Elizabeth Hospital NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
King's College Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Norfolk and Norwich University Hospital
City
Norwich
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30661255
Citation
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 Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801. doi: 10.1002/hep.30509. Epub 2019 Mar 10.
Results Reference
result
PubMed Identifier
35934287
Citation
Trauner M, Bowlus CL, Gulamhusein A, Hameed B, Caldwell SH, Shiffman ML, Landis C, Muir AJ, Billin A, Xu J, Liu X, Lu X, Chung C, Myers RP, Kowdley KV. Safety and Sustained Efficacy of the Farnesoid X Receptor (FXR) Agonist Cilofexor Over a 96-Week Open-label Extension in Patients With PSC. Clin Gastroenterol Hepatol. 2023 Jun;21(6):1552-1560.e2. doi: 10.1016/j.cgh.2022.07.024. Epub 2022 Aug 4.
Results Reference
derived
Learn more about this trial
Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
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