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

NCT02943460 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-428-40252016-002442-23
• Study Type: interventional
• Target: 52
• Locations: 4 countries
• Sites: 23

Brief Summary

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

Conditions

Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase

  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

  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

  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)

Study Arms (4)

Cilofexor 100 mg (Blinded Study Phase)

EXPERIMENTAL

Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks

Drug: Cilofexor; Drug: Placebo to match cilofexor

Cilofexor 30 mg (Blinded Study Phase)

EXPERIMENTAL

Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks

Drug: Cilofexor; Drug: Placebo to match cilofexor

Placebo (Blinded Study Phase)

PLACEBO COMPARATOR

Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks

Drug: Placebo to match cilofexor

Cilofexor (Open Label Extension Phase)

EXPERIMENTAL

Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks.

Drug: Cilofexor

Interventions

Cilofexor DRUG

Tablet(s) administered orally once daily with food

Also known as: GS-9674

Cilofexor (Open Label Extension Phase); Cilofexor 100 mg (Blinded Study Phase); Cilofexor 30 mg (Blinded Study Phase)

Placebo to match cilofexor DRUG

Tablet(s) administered orally once daily with food

Cilofexor 100 mg (Blinded Study Phase); Cilofexor 30 mg (Blinded Study Phase); Placebo (Blinded Study Phase)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (23)

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Florida Digestive Health Specialists

Lakewood Rch, Florida, 34211, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Minnesota Gastroenterology, P.A.

Saint Paul, Minnesota, 55117, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Intermountain Medical Center - Transplant Services

Murray, Utah, 84107, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Bon Secours St. Mary's Hospital of Richmond, Inc.

Richmond, Virginia, 23226, United States

Location

McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Swedish Organ Transplant and Liver Center

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Universitätsklinik Klinik für Innere Medizin III

Vienna, Austria

Location

University of Calgary Liver Unit (Heritage Medical Research Clinic)

Calgary, Alberta, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

New Queen Elizabeth Hospital NHS Foundation Trust

Birmingham, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30661255 RESULT

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

cilofexor

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: October 24, 2016
• Study Start: November 29, 2016
• Primary Completion: February 28, 2018
• Study Completion: May 18, 2020
• Last Updated: June 7, 2021
• Results First Posted: March 12, 2019

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (16); AU (1); CA (2); GB (4)