Clinical trial NCT04060147: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Primary Sclerosing Cholangitis
Compensated Cirrhosis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-08-16
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 12 weeks plus 30 days
measure: Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: First dose date up to 12 weeks plus 30 days
measure: Percentage of Participants Who Experienced Laboratory Abnormalities
timeFrame: First dose date up to 12 weeks plus 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco, Liver Clinic
state: California
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Shreveport
country: United States
facility: Louisiana Research Center, LLC
state: Louisiana
city: Maplewood
country: United States
facility: Minnesota Gastroenterology, PA
state: Minnesota
city: Manhasset
country: United States
facility: Northwell Health Center for Liver Diseases and Transplantation
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
state: Virginia
city: Richmond
country: United States
facility: VCU Clinical Research Services Unit (CRSU) [Patient Site Address]
state: Virginia
city: Seattle
country: United States
facility: University of Washington at Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: