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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Primary Sclerosing Cholangitis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02943460

GS-US-428-4025

2016-002442-23 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 52 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous transhepatic cholangiogram (PTC)) within the previous 12 months
• Serum alkaline phosphatase (ALP) > 1.67 x upper limit of the normal range (ULN)
• For individuals on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable for at least 12 months prior to screening through the end of treatment. For individuals not on UDCA, no UDCA use for at least 12 months before screening through the end of treatment
• For individuals being administered biologic treatments (eg, antitumor necrosis factor (TNF) or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids, the dose must have been stable at least 3 months prior to screening and anticipated to remain stable throughout the trial
• 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) > 10 x ULN

• Total bilirubin > 2 x ULN

• International normalized ratio (INR) > 1.2 unless on anticoagulant therapy

• Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography)

• Other causes of liver disease including secondary sclerosing cholangitis and viral, metabolic, alcoholic, and other autoimmune conditions. Individuals 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;

• Ascending cholangitis within 60 days of screening

• Presence of a percutaneous drain or bile duct stent

• 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)
  • Prior history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
  • Liver stiffness > 14.4 kilopascal (kPa) by FibroScan

• Current, active inflammatory bowel disease (IBD) defined as a partial Mayo score of > 1 and/or a score on the Rectal Bleeding domain > 0.

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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52 participants in 4 patient groups, including a placebo group

Cilofexor 100 mg (Blinded Study Phase)

Experimental group

Description:

Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks

Treatment:

Drug: Cilofexor

Drug: Placebo to match cilofexor

Cilofexor 30 mg (Blinded Study Phase)

Experimental group

Description:

Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks

Treatment:

Drug: Cilofexor

Drug: Placebo to match cilofexor

Placebo (Blinded Study Phase)

Placebo Comparator group

Description:

Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks

Treatment:

Drug: Placebo to match cilofexor

Cilofexor (Open Label Extension Phase)

Experimental group

Description:

Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks.

Treatment:

Drug: Cilofexor