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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

Tracking Information
First Submitted Date  ICMJE June 13, 2016
First Posted Date  ICMJE October 24, 2016
Results First Submitted Date  ICMJE February 21, 2019
Results First Posted Date  ICMJE March 12, 2019
Last Update Posted Date July 30, 2019
Actual Study Start Date  ICMJE November 29, 2016
Actual Primary Completion Date February 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History Complete list of historical versions of study NCT02943460 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Primary Sclerosing Cholangitis
Intervention  ICMJE
  • 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  ICMJE
  • 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 * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 15, 2017)
52
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2016)
50
Estimated Study Completion Date  ICMJE April 2020
Actual Primary Completion Date February 28, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Canada,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02943460
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP