Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02943460
Recruitment Status : Active, not recruiting
First Posted : October 24, 2016
Results First Posted : March 12, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Primary Sclerosing Cholangitis Drug: Cilofexor Drug: Placebo to match Cilofexor Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 29, 2016
Actual Primary Completion Date : February 28, 2018
Estimated Study Completion Date : April 2020


Arm Intervention/treatment
Experimental: Cilofexor 30 mg (Blinded Study Phase)
Cilofexor 30 mg + placebo to match Cilofexor 100 mg for 12 weeks
Drug: Cilofexor
Tablet(s) administered orally once daily
Other Name: GS-9674

Drug: Placebo to match Cilofexor
Tablet(s) administered orally once daily

Experimental: Cilofexor 100 mg (Blinded Study Phase)
Cilofexor 100 mg + placebo to match Cilofexor 30 mg for 12 weeks
Drug: Cilofexor
Tablet(s) administered orally once daily
Other Name: GS-9674

Drug: Placebo to match Cilofexor
Tablet(s) administered orally once daily

Placebo Comparator: Placebo (Blinded Study Phase)
Placebo to match Cilofexor 30 mg + placebo to match Cilofexor 100 mg for 12 weeks
Drug: Placebo to match Cilofexor
Tablet(s) administered orally once daily

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.
Drug: Cilofexor
Tablet(s) administered orally once daily
Other Name: GS-9674




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02943460


Locations
Layout table for location information
United States, California
Sacramento, California, United States
San Francisco, California, United States
United States, Colorado
Aurora, Colorado, United States
United States, Florida
Lakewood Ranch, Florida, United States
Miami, Florida, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Minnesota
Saint Paul, Minnesota, United States
United States, North Carolina
Durham, North Carolina, United States
United States, Texas
Dallas, Texas, United States
United States, Utah
Murray, Utah, United States
United States, Virginia
Charlottesville, Virginia, United States
Newport News, Virginia, United States
Richmond, Virginia, United States
United States, Washington
Seattle, Washington, United States
Austria
Vienna, Austria
Canada, Alberta
Calgary, Alberta, Canada
Canada, Ontario
Toronto, Ontario, Canada
United Kingdom
Birmingham, United Kingdom
London, United Kingdom
Norwich, United Kingdom
Sponsors and Collaborators
Gilead Sciences
Investigators
Layout table for investigator information
Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol: Original  [PDF] June 29, 2016
Study Protocol: Amendment 1  [PDF] September 30, 2016
Study Protocol: Amendment 2  [PDF] December 21, 2016
Study Protocol: Amendment 3  [PDF] February 9, 2017
Statistical Analysis Plan  [PDF] March 21, 2018


Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02943460     History of Changes
Other Study ID Numbers: GS-US-428-4025
2016-002442-23 ( EudraCT Number )
First Posted: October 24, 2016    Key Record Dates
Results First Posted: March 12, 2019
Last Update Posted: July 30, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Cholangitis
Cholangitis, Sclerosing
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases