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

May 11, 2021 updated by: Gilead Sciences

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria
        • Universitätsklinik Klinik für Innere Medizin III
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • University of Calgary Liver Unit (Heritage Medical Research Clinic)
    • Ontario
      • Toronto, Ontario, Canada, M6H 3M1
        • Toronto Liver Centre
  • United Kingdom
      • Birmingham, United Kingdom
        • New Queen Elizabeth Hospital NHS Foundation Trust
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, United Kingdom, SE5 9RS
        • King's College Hospital NHS Foundation Trust
      • Norwich, United Kingdom, NR4 7UY
        • Norfolk and Norwich University Hospital
  • United States
    • California
      • Sacramento, California, United States, 95817
        • University of California, Davis Medical Center
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver
    • Florida
      • Lakewood Ranch, Florida, United States, 34211
        • Florida Digestive Health Specialists
      • Miami, Florida, United States, 33136
        • Schiff Center for Liver Diseases/University of Miami
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health University Hospital
    • Minnesota
      • Saint Paul, Minnesota, United States, 55117
        • Minnesota Gastroenterology, P.A.
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Texas
      • Dallas, Texas, United States, 75203
        • The Liver Institute At Methodist Dallas Medical Center
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center - Transplant Services
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
      • Richmond, Virginia, United States, 23249
        • McGuire VA Medical Center
      • Richmond, Virginia, United States, 23226
        • Bon Secours St. Mary's Hospital of Richmond, Inc.
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington
      • Seattle, Washington, United States, 98104
        • Swedish Organ Transplant and Liver Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cilofexor 100 mg (Blinded Study Phase)
Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks
Drug: Cilofexor
Tablet(s) administered orally once daily with food
Other Names:
  • GS-9674
Drug: Placebo to match cilofexor
Tablet(s) administered orally once daily with food
Experimental: Cilofexor 30 mg (Blinded Study Phase)
Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks
Drug: Cilofexor
Tablet(s) administered orally once daily with food
Other Names:
  • GS-9674
Drug: Placebo to match cilofexor
Tablet(s) administered orally once daily with food
Placebo Comparator: Placebo (Blinded Study Phase)
Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks
Drug: Placebo to match cilofexor
Tablet(s) administered orally once daily with food
Experimental: Cilofexor (Open Label Extension Phase)
Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks.
Drug: Cilofexor
Tablet(s) administered orally once daily with food
Other Names:
  • GS-9674

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase
Time Frame: 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.
First dose date up to last dose date plus 30 days (Up to 17 weeks)
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase
Time Frame: 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.
First dose date up to last dose date plus 30 days (Up to 17 weeks)
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase
Time Frame: 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).
First dose date up to last dose date plus 30 days (Up to 17 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2016

Primary Completion (Actual)

February 28, 2018

Study Completion (Actual)

May 18, 2020

Study Registration Dates

First Submitted

June 13, 2016

First Submitted That Met QC Criteria

October 21, 2016

First Posted (Estimate)

October 24, 2016

Study Record Updates

Last Update Posted (Actual)

June 7, 2021

Last Update Submitted That Met QC Criteria

May 11, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-428-4025
  • 2016-002442-23 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Primary Sclerosing Cholangitis

Clinical Trials on Cilofexor

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe