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

Phase 2

Terminated

• Conditions: Primary Biliary Cholangitis
• Interventions: Drug: Cilofexor; Drug: Placebo to match cilofexor

• Registration Number: NCT02943447
• Lead Sponsor: Gilead Sciences

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-13
• Study First Submitted QC: 2016-10-21
• Study First Posted: 2016-10-24
• Study Start: 2016-12-01
• Disposition First Submitted: 2019-06-03
• Disposition First Submitted QC: 2019-06-03
• Disposition First Posted: 2019-06-05
• Primary Completion: 2019-09-04
• Study Completion: 2019-09-04
• Results First Submitted: 2019-12-19
• Results First Submitted QC: 2019-12-19
• Results First Posted: 2020-01-13
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-03
• Last Update Posted: 2020-09-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 71

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cilofexor 100 mg (Blinded Study Phase)	Placebo to match cilofexor	Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.
Cilofexor 30 mg (Blinded Study Phase)	Cilofexor	Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Cilofexor 30 mg (Blinded Study Phase)	Placebo to match cilofexor	Cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Placebo (Blinded Study Phase)	Placebo to match cilofexor	Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for 12 weeks.
Cilofexor 100 mg (Blinded Study Phase)	Cilofexor	Cilofexor 100 mg + placebo to match cilofexor 30 mg for 12 weeks.
Cilofexor (Open Label Extension Phase)	Cilofexor	Following the Blinded Study Phase, eligible participants may have the option to receive open-label cilofexor 100 mg for an additional 96 weeks.

Primary Outcome Measures

Name	Time	Method
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 Who Experienced Graded Laboratory Abnormalities in the OLE Phase	First dose date in the OLE phase up to last dose date (Maximum: 97.4 weeks) + 30 days	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 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	First dose date up to Week 12 + 30 days	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.