Clinical trial NCT02943460: Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
Official title: A Phase 2, Randomized, Double-Blind, Placebo Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Sclerosing Cholangitis Without Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-10-24
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary sclerosing cholangitis (PSC).


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous transhepatic cholangiogram (PTC)) within the previous 12 months
* Serum alkaline phosphatase (ALP) \> 1.67 x upper limit of the normal range (ULN)
* For individuals on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable for at least 12 months prior to screening through the end of treatment. For individuals not on UDCA, no UDCA use for at least 12 months before screening through the end of treatment
* For individuals being administered biologic treatments (eg, antitumor necrosis factor (TNF) or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids, the dose must have been stable at least 3 months prior to screening and anticipated to remain stable throughout the trial
* Screening FibroSURE/FibroTest® \<0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of total bilirubin.

Key Exclusion Criteria:

* Alanine aminotransferase (ALT) \> 10 x ULN
* Total bilirubin \> 2 x ULN
* International normalized ratio (INR) \> 1.2 unless on anticoagulant therapy
* Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography)
* Other causes of liver disease including secondary sclerosing cholangitis and viral, metabolic, alcoholic, and other autoimmune conditions. Individuals with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy;
* Ascending cholangitis within 60 days of screening
* Presence of a percutaneous drain or bile duct stent
* Use of fibrates or obeticholic acid within 3 months prior to screening through the end of treatment
* Cirrhosis of the liver as defined by any of the following:

  * Historical liver biopsy demonstrating cirrhosis (eg, Ludwig stage 4 or Ishak stage ≥ 5)
  * Prior history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
  * Liver stiffness \> 14.4 kilopascal (kPa) by FibroScan
* Current, active inflammatory bowel disease (IBD) defined as a partial Mayo score of \> 1 and/or a score on the Rectal Bleeding domain \> 0.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase
timeFrame: First dose date up to last dose date plus 30 days (Up to 17 weeks)
measure: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase
timeFrame: First dose date up to last dose date plus 30 days (Up to 17 weeks)
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase
timeFrame: First dose date up to last dose date plus 30 days (Up to 17 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Lakewood Ranch
country: United States
facility: Florida Digestive Health Specialists
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Saint Paul
country: United States
facility: Minnesota Gastroenterology, P.A.
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center - Transplant Services
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond, Inc.
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Organ Transplant and Liver Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vienna
country: Austria
facility: Universitätsklinik Klinik für Innere Medizin III
city: Calgary
country: Canada
facility: University of Calgary Liver Unit (Heritage Medical Research Clinic)
state: Alberta
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Birmingham
country: United Kingdom
facility: New Queen Elizabeth Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Trauner M, Gulamhusein A, Hameed B, Caldwell S, Shiffman ML, Landis C, Eksteen B, Agarwal K, Muir A, Rushbrook S, Lu X, Xu J, Chuang JC, Billin AN, Li G, Chung C, Subramanian GM, Myers RP, Bowlus CL, Kowdley KV. The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801. doi: 10.1002/hep.30509. Epub 2019 Mar 10.
citation: Trauner M, Bowlus CL, Gulamhusein A, Hameed B, Caldwell SH, Shiffman ML, Landis C, Muir AJ, Billin A, Xu J, Liu X, Lu X, Chung C, Myers RP, Kowdley KV. Safety and Sustained Efficacy of the Farnesoid X Receptor (FXR) Agonist Cilofexor Over a 96-Week Open-label Extension in Patients With PSC. Clin Gastroenterol Hepatol. 2023 Jun;21(6):1552-1560.e2. doi: 10.1016/j.cgh.2022.07.024. Epub 2022 Aug 4.