Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis

A Proof-of-Concept, Open-Label Study Evaluating the Safety and Tolerability of Cilofexor in Subjects With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis

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.

Study Overview

• Status: Terminated
• Conditions: Primary Sclerosing Cholangitis; Compensated Cirrhosis
• Intervention / Treatment: Drug: Cilofexor

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
  • California
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • San Francisco, California, United States, 94143
      • University of California San Francisco, Liver Clinic
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health University Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center, LLC
  • Minnesota
    • Maplewood, Minnesota, United States, 55117
      • Minnesota Gastroenterology, PA
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health Center for Liver Diseases and Transplantation
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Texas
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
    • Richmond, Virginia, United States, 23226
      • Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
    • Richmond, Virginia, United States, 23298
      • VCU Clinical Research Services Unit (CRSU) [Patient Site Address]
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest
    • Seattle, Washington, United States, 98104
      • University of Washington at Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cilofexor; Participants will receive escalating doses of cilofexor 30 mg, 60 mg, and 100 mg.	Drug: Cilofexor; Tablets administered orally once daily; Other Names: GS-9674; CILO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	First dose date up to 12 weeks plus 30 days
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.	First dose date up to 12 weeks plus 30 days
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.	First dose date up to 12 weeks plus 30 days

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Actual): September 2, 2021
• Study Completion (Actual): September 2, 2021

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 16, 2019

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Fibrosis; Liver Cirrhosis; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: GS-US-428-5443

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