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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Primary Biliary Cholangitis

Treatments: Drug: Placebo to match cilofexor; Drug: Cilofexor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02943447

2016-002443-42 (EudraCT Number)

GS-US-427-4024

Details and patient eligibility

About

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

Enrollment: 71 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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71 participants in 4 patient groups, including a placebo group

Cilofexor 30 mg (Blinded Study Phase)

Experimental group

Description:

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

Treatment:

Drug: Placebo to match cilofexor

Drug: Cilofexor

Cilofexor 100 mg (Blinded Study Phase)

Experimental group

Description:

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

Treatment:

Drug: Placebo to match cilofexor

Drug: Cilofexor

Placebo (Blinded Study Phase)

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo to match cilofexor

Cilofexor (Open Label Extension Phase)

Experimental group

Description:

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

Treatment:

Drug: Cilofexor