A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid

This is a multi-center, randomized (treatment will be assigned by chance),
placebo-controlled (an inactive substance will be compared with the test drug to see whether
the drug has a real effect), parallel-group (two or more groups of patients will receive
different treatments) study that will consist of two parts. Part 1 will be an open-label
(all participants will know the identity of the treatment) proof-of-concept study. Part 2
will be contingent on the results of Part 1 and will be double-blind (investigators and
patients will not know what treatment is being given) and will evaluate the efficacy and
safety of ustekinumab in patients with primary biliary cirrhosis (PBC) who had an inadequate
response to ursodeoxycholic acid. The duration of participation in the study for an
individual participant may be up to 216 weeks. Patient safety will be monitored. Part 1:
ustekinumab, 90mg subcutaneous (SC) at Weeks 0 and 4 and every 8 weeks through Week 20; Part
2: Depending on Part 1 results, either (ustekinumab 90mg or 45mg or placebo) or (ustekinumab
90mg or 180mg or placebo) SC at Weeks 0 and 4 and every 8 weeks through Week 20; Long-term
Extension (including Part 1 and Part 2): beginning at Week 28, every 8 weeks with initially
assigned dose until the extension dose has been selected; then every 8 weeks through Week
196 with the selected dose.

Inclusion Criteria:

- Have proven or are likely to have Primary Biliary Cirrhosis (PBC)

- Be on a stable dose of ursodeoxycholic acid for at least 6 months prior to Week 0

- Have screening alkaline phosphatase (ALP) level > 1.67 ULN (the upper limit of
normal)

- Have screening laboratory test results within protocol-specified limits

- Have no history of latent or active tuberculosis (TB) prior to screening and no signs
or symptoms suggestive of active TB upon medical history and/or physical examination.

Exclusion Criteria:

- Has history of gastrointestinal bleeding, secondary to portal hypertension, hepatic
encephalopathy, or ascites requiring treatment with diuretics

- Has a screening direct bilirubin > 1.0 mg/dL

- Has a previous liver histology with a diagnosis of steatohepatitis or has a high risk
of nonalcoholic steatohepatitis

- Has a previous liver histology with a diagnosis of chronic autoimmune hepatitis or
has a high risk of autoimmune hepatitis overlap syndrome

- Testing positive for surface antigen (HBsAg+), regardless of the results of other
hepatitis B tests

- Have used colchicine, methotrexate (MTX), azathioprine (AZA), or systemic
corticosteroids within 3 months prior to the first administration of study drug.