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

Primary Sclerosing Cholangitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04060147
• Other study ID #: GS-US-428-5443
• Status: Terminated
• Phase: Phase 1
• Start date: October 17, 2019
• Est. completion date: September 2, 2021

Study information

• Verified date: August 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: September 2, 2021
• Est. primary completion date: September 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Compensated Cirrhosis
• Fibrosis
• Liver Cirrhosis
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Cilofexor
Tablets administered orally once daily

Locations

Country	Name	City	State
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Arizona Liver Health	Chandler	Arizona
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	Indiana University Health University Hospital	Indianapolis	Indiana
United States	Northwell Health Center for Liver Diseases and Transplantation	Manhasset	New York
United States	Minnesota Gastroenterology, PA	Maplewood	Minnesota
United States	Schiff Center for Liver Diseases/University of Miami	Miami	Florida
United States	California Liver Research Institute	Pasadena	California
United States	Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	VCU Clinical Research Services Unit (CRSU) [Patient Site Address]	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California San Francisco, Liver Clinic	San Francisco	California
United States	Liver Institute Northwest	Seattle	Washington
United States	University of Washington at Harborview Medical Center	Seattle	Washington
United States	Louisiana Research Center, LLC	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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