Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis

Phase 2

Completed

• Conditions: Primary Sclerosing Cholangitis
• Interventions: Drug: Cilofexor; Drug: Placebo to match cilofexor

• Registration Number: NCT02943460
• Lead Sponsor: Gilead Sciences

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 available

Study Timeline

• Study First Submitted: 2016-06-13
• Study First Submitted QC: 2016-10-21
• Study First Posted: 2016-10-24
• Study Start: 2016-11-29
• Primary Completion: 2018-02-28
• Results First Submitted: 2019-02-21
• Results First Submitted QC: 2019-02-21
• Results First Posted: 2019-03-12
• Study Completion: 2020-05-18
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-11
• Last Update Posted: 2021-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cilofexor 100 mg (Blinded Study Phase)	Placebo to match cilofexor	Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks
Placebo (Blinded Study Phase)	Placebo to match cilofexor	Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks
Cilofexor 30 mg (Blinded Study Phase)	Placebo to match cilofexor	Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks
Cilofexor 100 mg (Blinded Study Phase)	Cilofexor	Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks
Cilofexor 30 mg (Blinded Study Phase)	Cilofexor	Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks
Cilofexor (Open Label Extension Phase)	Cilofexor	Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase	First dose date up to last dose date plus 30 days (Up to 17 weeks)	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	First dose date up to last dose date plus 30 days (Up to 17 weeks)	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	First dose date up to last dose date plus 30 days (Up to 17 weeks)	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 (and prior to or on the first dose date of the OLE phase). 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).

Trial Locations

Locations (23)

The Liver Institute at Methodist Dallas Medical Center; 🇺🇸 Dallas, Texas, United States

Universitätsklinik Klinik für Innere Medizin III; 🇦🇹 Vienna, Austria

University of Calgary Liver Unit (Heritage Medical Research Clinic); 🇨🇦 Calgary, Alberta, Canada

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

University of California, Davis Medical Center; 🇺🇸 Sacramento, California, United States

Florida Digestive Health Specialists; 🇺🇸 Lakewood Ranch, Florida, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Indiana University Health University Hospital; 🇺🇸 Indianapolis, Indiana, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Intermountain Medical Center - Transplant Services; 🇺🇸 Murray, Utah, United States

Bon Secours St. Mary's Hospital of Richmond, Inc.; 🇺🇸 Richmond, Virginia, United States

Swedish Organ Transplant and Liver Center; 🇺🇸 Seattle, Washington, United States

Toronto Liver Centre; 🇨🇦 Toronto, Ontario, Canada

King's College Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

Schiff Center for Liver Diseases/University of Miami; 🇺🇸 Miami, Florida, United States

New Queen Elizabeth Hospital NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Royal Free Hospital; 🇬🇧 London, United Kingdom

McGuire VA Medical Center; 🇺🇸 Richmond, Virginia, United States

Norfolk and Norwich University Hospital; 🇬🇧 Norwich, United Kingdom

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Minnesota Gastroenterology, P.A.; 🇺🇸 Saint Paul, Minnesota, United States