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

NCT ID: NCT01389973

Last Updated: 2016-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2013-06-30

Brief Summary

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.

Detailed 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.

Conditions

Primary Biliary Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Open-label: ustekinumab 90 mg

Group Type: EXPERIMENTAL

ustekinumab 90 mg

Intervention Type: DRUG

Subcutaneous injections of ustekinumb 90 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Double-blind: ustekinumab 45 mg

Group Type: EXPERIMENTAL

ustekinumab 45 mg

Intervention Type: DRUG

Subcutaneous injections of ustekinumb 45 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Double-blind: ustekinumab 90 mg

Group Type: EXPERIMENTAL

ustekinumab 90 mg

Intervention Type: DRUG

Subcutaneous injections of ustekinumb 90 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Double-blind: ustekinumb 180 mg

Group Type: EXPERIMENTAL

ustekinumab 180 mg

Intervention Type: DRUG

Subcutaneous injections of ustekinumb 180 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Double-blind: placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subcutaneous injections of placebo at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Interventions

ustekinumab 90 mg

Subcutaneous injections of ustekinumb 90 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Intervention Type: DRUG

ustekinumab 45 mg

Subcutaneous injections of ustekinumb 45 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Intervention Type: DRUG

ustekinumab 180 mg

Subcutaneous injections of ustekinumb 180 mg at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Intervention Type: DRUG

Placebo

Subcutaneous injections of placebo at Weeks 0 and 4 and every 8 weeks until the dose for the Long-Term Extension has been selected then every 8 weeks through Week 196 with the selected dose.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Jacksonville, Florida, United States

Miami, Florida, United States

Naples, Florida, United States

Tupelo, Mississippi, United States

New York, New York, United States

Houston, Texas, United States

Vancouver, British Columbia, Canada

Halifax, Nova Scotia, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Countries

United States; Canada

References

Mousa HS, Lleo A, Invernizzi P, Bowlus CL, Gershwin ME. Advances in pharmacotherapy for primary biliary cirrhosis. Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.

Reference Type: DERIVED

PMID: 25543678 (View on PubMed)

Other Identifiers

CNTO1275PBC2001

Identifier Type: OTHER

Identifier Source: secondary_id

2011-000554-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR018748

Identifier Type: -

Identifier Source: org_study_id