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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Primary Biliary Cirrhosis

Treatments: Drug: ustekinumab 90 mg; Drug: ustekinumab 45 mg; Drug: ustekinumab 180 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01389973

CNTO1275PBC2001 (Other Identifier)

CR018748

2011-000554-31 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of ustekinumab in patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid.

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 5 patient groups, including a placebo group

Open-label: ustekinumab 90 mg

Experimental group

Treatment:

Drug: ustekinumab 90 mg

Double-blind: ustekinumab 45 mg

Experimental group

Treatment:

Drug: ustekinumab 45 mg

Double-blind: ustekinumab 90 mg

Experimental group

Treatment:

Drug: ustekinumab 90 mg

Double-blind: ustekinumb 180 mg

Experimental group

Treatment:

Drug: ustekinumab 180 mg

Double-blind: placebo

Placebo Comparator group

Treatment:

Drug: Placebo