Clinical trial NCT02943447: Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Biliary Cholangitis Without Cirrhosis
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Biliary Cholangitis Without Cirrhosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Biliary Cholangitis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-10-24
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary biliary cholangitis (PBC).


Eligibility criteria: Key Inclusion Criteria:

* Meets all of the following conditions

  * Definite or probable PBC as defined by at least 2 of the 3 following criteria:

    * Serum alkaline phosphatase (ALP) \> the upper limit of normal (ULN)
    * Presence of anti-mitochondrial antibodies (AMA) in serum (≥ 1:40 on immunofluorescence)
    * Liver histological findings consistent with PBC including nonsuppurative, destructive cholangitis affecting mainly the interlobular bile and septal bile ducts
  * Serum ALP \> 1.67 x ULN and/or total bilirubin \>ULN but ≤ 2 x ULN
  * Ursodeoxycholic acid (UDCA) use at a stable dose for at least 12 months or intolerant of UDCA with no UDCA use for at least 12 months before screening
* 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) \> 5 x ULN
* Total bilirubin \> 2 x ULN
* International normalized ratio (INR) \> 1.2 unless on anticoagulant therapy
* Other causes of liver disease including viral, metabolic, alcoholic, and other autoimmune conditions. Participants 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.
* 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)
  * History of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
  * Liver stiffness \> 16.9 kPa by FibroScan®

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
timeFrame: First dose date up to Week 12 + 30 days
measure: Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase
timeFrame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
measure: Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase
timeFrame: First dose date up to Week 12 + 30 days
measure: Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase
timeFrame: First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Lakewood Ranch
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Saint Paul
country: United States
state: Minnesota
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Charlottesville
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Graz
country: Austria
state: Steiermark
city: Wien
country: Austria
state: Vienna
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Toronto
country: Canada
state: Ontario
city: Vaughan
country: Canada
state: Ontario
city: Birmingham
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: Norwich
country: United Kingdom
state: England
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Kowdley KV, Minuk GY, Pagadala MR, Gulamhusein A, Swain MG, Neff GW, et al. The Nonsteroidal Farnesoid X Receptor (FXR) Agonist Cilofexor Improves Liver Biochemistry in Patients with Primary Biliary Cholangitis (PBC): A Phase 2, Randomized, Placebo-Controlled Trial [Abstract 45]. Hepatology AASLD Abstracts 2019;70 (Suppl 1):31A-2A.