Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis (PSC-Phase 2)

• ClinicalTrials.gov Identifier: NCT02943460
• Recruitment Status: Completed
• First Posted: October 24, 2016
• Results First Posted: March 12, 2019
• Last Update Posted: June 9, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: June 13, 2016
• First Posted Date: October 24, 2016
• Results First Submitted Date: February 21, 2019
• Results First Posted Date: March 12, 2019
• Last Update Posted Date: June 9, 2020
• Actual Study Start Date: November 29, 2016
• Actual Primary Completion Date: February 28, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2019)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase [ Time Frame: Up to 12 weeks plus 30 days ]
  Treatment-emergent adverse events occurring during the Blinded Phase were defined as 1 or both of the following: 1) Any adverse events (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 in the Blinded Phase (and before the first dosing date in the Open Label Extension (OLE) Phase), or 2) Any AEs leading to premature discontinuation of study drug in the Blinded Phase.
• Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase [ Time Frame: Up to 12 weeks plus 30 days ]
  A serious adverse event was defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
• Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase [ Time Frame: Up to 12 weeks plus 30 days ]
  Treatment-emergent laboratory abnormalities occurring during the Blinded Phase were 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 in the Blinded Phase plus 30 days. The Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 was used for assigning toxicity grades (0 to 4, with higher grades indicating more severity).

Original Primary Outcome Measures (submitted: October 21, 2016)

• Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to 12 weeks plus 30 days ]
• Incidence of Treatment-Emergent Serious Adverse Events [ Time Frame: Up to 12 weeks plus 30 days ]
• Incidence of treatment-emergent laboratory abnormalities [ Time Frame: Up to 12 weeks plus 30 days ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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 Cilofexor in Subjects With Primary Sclerosing Cholangitis Without Cirrhosis
• Brief Summary: The primary objective of this study is to evaluate the safety and tolerability of Cilofexor in adults with primary sclerosing cholangitis (PSC).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Primary Sclerosing Cholangitis

Intervention

• Drug: Cilofexor
  Tablet(s) administered orally once daily
  Other Name: GS-9674
• Drug: Placebo to match Cilofexor
  Tablet(s) administered orally once daily

Study Arms

• Experimental: Cilofexor 30 mg (Blinded Study Phase)
  Cilofexor 30 mg + placebo to match Cilofexor 100 mg for 12 weeks
  Interventions:

  • Drug: Cilofexor
  • Drug: Placebo to match Cilofexor
• Experimental: Cilofexor 100 mg (Blinded Study Phase)
  Cilofexor 100 mg + placebo to match Cilofexor 30 mg for 12 weeks
  Interventions:

  • Drug: Cilofexor
  • Drug: Placebo to match Cilofexor
• Placebo Comparator: Placebo (Blinded Study Phase)
  Placebo to match Cilofexor 30 mg + placebo to match Cilofexor 100 mg for 12 weeks
  Intervention: Drug: Placebo to match Cilofexor
• Experimental: Cilofexor (Open Label Extension Phase)
  Following the Blinded Study Phase, eligible participants may have the option to receive Cilofexor for an additional 96 weeks.
  Intervention: Drug: Cilofexor

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 15, 2017): 52
• Original Estimated Enrollment (submitted: October 21, 2016): 50
• Actual Study Completion Date: May 18, 2020
• Actual Primary Completion Date: February 28, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, United Kingdom, United States

Administrative Information

• NCT Number: NCT02943460
• Other Study ID Numbers: GS-US-428-4025; 2016-002442-23 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: May 2020