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Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Biliary Cholangitis Without Cirrhosis (PBC-Phase 2)

Primary Purpose

Primary Biliary Cholangitis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cilofexor
Placebo to match cilofexor
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cholangitis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

Cilofexor 30 mg (Blinded Study Phase)

Cilofexor 100 mg (Blinded Study Phase)

Placebo (Blinded Study Phase)

Cilofexor (Open Label Extension Phase)

Arm Description

Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.

Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.

Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.

Following the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.

Secondary Outcome Measures

Full Information

First Posted
June 13, 2016
Last Updated
September 3, 2020
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02943447
Brief Title
Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Biliary Cholangitis Without Cirrhosis
Acronym
PBC-Phase 2
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

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated because of the availability of alternate therapies for primary biliary cholangitis (PBC).
Study Start Date
December 1, 2016 (Actual)
Primary Completion Date
September 4, 2019 (Actual)
Study Completion Date
September 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cholangitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cilofexor 30 mg (Blinded Study Phase)
Arm Type
Experimental
Arm Description
Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Arm Title
Cilofexor 100 mg (Blinded Study Phase)
Arm Type
Experimental
Arm Description
Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.
Arm Title
Placebo (Blinded Study Phase)
Arm Type
Placebo Comparator
Arm Description
Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Arm Title
Cilofexor (Open Label Extension Phase)
Arm Type
Experimental
Arm Description
Following the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks.
Intervention Type
Drug
Intervention Name(s)
Cilofexor
Other Intervention Name(s)
GS-9674
Intervention Description
Tablet(s) administered orally once daily, with food
Intervention Type
Drug
Intervention Name(s)
Placebo to match cilofexor
Intervention Description
Tablet(s) administered orally once daily, with food
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase
Time Frame
First dose date up to Week 12 + 30 days
Title
Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase
Time Frame
First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days
Title
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the Blinded Study Phase
Description
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Time Frame
First dose date up to Week 12 + 30 days
Title
Percentage of Participants Who Experienced Graded Laboratory Abnormalities in the OLE Phase
Description
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Time Frame
First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Lakewood Ranch
State/Province
Florida
ZIP/Postal Code
34211
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Graz
State/Province
Steiermark
ZIP/Postal Code
8036
Country
Austria
City
Wien
State/Province
Vienna
ZIP/Postal Code
1090
Country
Austria
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0T6
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
City
Vaughan
State/Province
Ontario
ZIP/Postal Code
L4L 4Y7
Country
Canada
City
Birmingham
State/Province
England
ZIP/Postal Code
B215 2GW
Country
United Kingdom
City
London
State/Province
England
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
City
London
State/Province
England
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
City
Norwich
State/Province
England
ZIP/Postal Code
NR4 7UY
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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.
Results Reference
result

Learn more about this trial

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

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