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

Study Overview
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Brief Summary
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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.

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

Conditions
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Primary Sclerosing Cholangitis, Compensated Cirrhosis

Intervention / Treatment
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* Drug: Cilofexor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |