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

NCT02943447 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-427-40242016-002443-42
• Study Type: interventional
• Target: 71
• Locations: 4 countries
• Sites: 25

Brief Summary

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

Conditions

Primary Biliary Cholangitis

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) in the Blinded Study Phase

  First dose date up to Week 12 + 30 days

• Percentage of Participants Experiencing TEAEs and TESAEs in the Open-Label Extension (OLE) Phase

  First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days

• 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.

  First dose date up to Week 12 + 30 days

• 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.

  First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days

Study Arms (4)

Cilofexor 30 mg (Blinded Study Phase)

EXPERIMENTAL

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

Drug: Cilofexor; Drug: Placebo to match cilofexor

Cilofexor 100 mg (Blinded Study Phase)

EXPERIMENTAL

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

Drug: Placebo to match cilofexor

Cilofexor (Open Label Extension Phase)

EXPERIMENTAL

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

• 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.

You may not qualify if:

• 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®

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (25)

Unknown Facility

Sacramento, California, 95817, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Lakewood Rch, Florida, 34211, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Marietta, Georgia, 30060, United States

Location

Unknown Facility

Saint Paul, Minnesota, 55114, United States

Location

Unknown Facility

Arlington, Texas, 76012, United States

Location

Unknown Facility

Dallas, Texas, 75203, United States

Location

Unknown Facility

Dallas, Texas, 75246, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Charlottesville, Virginia, 22908, United States

Location

Unknown Facility

Newport News, Virginia, 23602, United States

Location

Unknown Facility

Seattle, Washington, 98104, United States

Location

Unknown Facility

Graz, Styria, 8036, Austria

Location

Unknown Facility

Vienna, Vienna, 1090, Austria

Location

Unknown Facility

Calgary, Alberta, T2N 4Z6, Canada

Location

Unknown Facility

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Unknown Facility

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Unknown Facility

Winnipeg, Manitoba, R3E 0T6, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2C4, Canada

Location

Unknown Facility

Vaughan, Ontario, L4L 4Y7, Canada

Location

Unknown Facility

Birmingham, England, B215 2GW, United Kingdom

Location

Unknown Facility

London, England, NW3 2QG, United Kingdom

Location

Unknown Facility

London, England, SE5 9RS, United Kingdom

Location

Unknown Facility

Norwich, England, NR4 7UY, United Kingdom

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

cilofexor

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: December 1, 2016
• Primary Completion: September 4, 2019
• Study Completion: September 4, 2019
• Last Updated: September 22, 2020
• Results First Posted: January 13, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6); GB (4); US (13); AU (2)