Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
Primary Purpose
Primary Sclerosing Cholangitis, Compensated Cirrhosis
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cilofexor
Sponsored by
About this trial
This is an interventional treatment trial for Primary Sclerosing Cholangitis
Eligibility Criteria
Key Inclusion Criteria:
- Diagnosis PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC]) or liver biopsy
- Individuals have evidence of cirrhosis based on historical liver biopsy, abdominal imaging (MRI, CT, or Ultrasound), or a screening FibroScan®, ELF™, or FibroTest®.
Individual has the following laboratory parameters at the Screening visit, as determined by the central laboratory:
- Estimated glomerular filtration rate (eGFR) > 60 mL/min, as calculated by the Cockcroft-Gault equation
- ALT ≤ 5 x ULN
- Total 2 mg/dL, unless the individual is known to have Gilbert's syndrome or hemolytic anemia
- INR ≤ 1.4, unless due to therapeutic anticoagulation
- Platelet count ≥ 75,000/μL. Individuals with evidence of high-risk esophageal or gastric varices in the opinion of the investigator are excluded
- Negative anti-mitochondrial antibody
Key Exclusion Criteria:
Current or prior history of any of the following
- Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal hemorrhage
- Liver transplantation
- Cholangiocarcinoma or hepatocellular carcinoma (HCC).
- Model for End-stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
- Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
Current moderate to severely active inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis).
- Note: Individuals with IBD who currently have an external ostomy bag and/or proctocolectomy are not subject to this exclusion criterion and need not undergo IBD Symptom Severity Assessment.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Arizona Liver Health
- California Liver Research Institute
- University of California San Francisco, Liver Clinic
- Schiff Center for Liver Diseases/University of Miami
- Piedmont Atlanta Hospital
- Indiana University Health University Hospital
- Louisiana Research Center, LLC
- Minnesota Gastroenterology, PA
- Northwell Health Center for Liver Diseases and Transplantation
- University of Rochester Medical Center
- The Liver Institute at Methodist Dallas Medical Center
- University of Virginia Medical Center
- Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
- VCU Clinical Research Services Unit (CRSU) [Patient Site Address]
- University of Washington at Harborview Medical Center
- Liver Institute Northwest
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cilofexor
Arm Description
Participants will receive escalating doses of cilofexor 30 mg, 60 mg, and 100 mg.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Treatment-emergent adverse events (TEAEs) were either defined 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 or any AEs leading to premature discontinuation of study drug.
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs)
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death ; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs.
Percentage of Participants Who Experienced Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are 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 plus 30 days. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04060147
Brief Title
Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
Official Title
A Proof-of-Concept, Open-Label Study Evaluating the Safety and Tolerability of Cilofexor in Subjects With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
The study enrollment was terminated early by the sponsor due to recruitment challenges.
Study Start Date
October 17, 2019 (Actual)
Primary Completion Date
September 2, 2021 (Actual)
Study Completion Date
September 2, 2021 (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 assess the safety and tolerability of escalating doses of cilofexor (CILO) in participants with primary sclerosing cholangitis (PSC) and compensated cirrhosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis, Compensated Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cilofexor
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of cilofexor 30 mg, 60 mg, and 100 mg.
Intervention Type
Drug
Intervention Name(s)
Cilofexor
Other Intervention Name(s)
CILO, GS-9674
Intervention Description
Tablets administered orally once daily
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Description
Treatment-emergent adverse events (TEAEs) were either defined 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 or any AEs leading to premature discontinuation of study drug.
Time Frame
First dose date up to 12 weeks plus 30 days
Title
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs)
Description
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death ; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs.
Time Frame
First dose date up to 12 weeks plus 30 days
Title
Percentage of Participants Who Experienced Laboratory Abnormalities
Description
Treatment-emergent laboratory abnormalities are 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 plus 30 days. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.
Time Frame
First dose date up to 12 weeks plus 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Diagnosis PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC]) or liver biopsy
Individuals have evidence of cirrhosis based on historical liver biopsy, abdominal imaging [magnetic resonance imaging (MRI), computed tomography (CT), or Ultrasound], or a screening FibroScan®, enhanced liver fibrosis (ELF)™, or FibroTest®.
Individual has the following laboratory parameters at the Screening visit, as determined by the central laboratory:
Estimated glomerular filtration rate (eGFR) > 60 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal (ULN)
Total 2 milligram/deciliter (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
Platelet count ≥ 75,000/microliter (μL). Individuals with evidence of high-risk esophageal or gastric varices in the opinion of the investigator are excluded
Negative anti-mitochondrial antibody
Key Exclusion Criteria:
Current or prior history of any of the following
Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal hemorrhage
Liver transplantation
Cholangiocarcinoma or hepatocellular carcinoma (HCC).
Model for End-stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
Current moderate to severely active inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis).
Note: Individuals with IBD who currently have an external ostomy bag and/or proctocolectomy are not subject to this exclusion criterion and need not undergo IBD Symptom Severity Assessment.
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
Arizona Liver Health
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
California Liver Research Institute
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
University of California San Francisco, Liver Clinic
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
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
Piedmont Atlanta Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Indiana University Health University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Louisiana Research Center, LLC
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71105
Country
United States
Facility Name
Minnesota Gastroenterology, PA
City
Maplewood
State/Province
Minnesota
ZIP/Postal Code
55117
Country
United States
Facility Name
Northwell Health Center for Liver Diseases and Transplantation
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
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
University of Virginia Medical Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
VCU Clinical Research Services Unit (CRSU) [Patient Site Address]
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Washington at Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Liver Institute Northwest
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
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