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

Janssen Research & Development, LLC20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Primary Biliary Cirrhosis

Interventions

ustekinumab 90 mgDRUG

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.

ustekinumab 45 mgDRUG

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.

ustekinumab 180 mgDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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.

Locations (10)

Unnamed facility

Jacksonville, Florida, United States

Unnamed facility

Miami, Florida, United States

Unnamed facility

Naples, Florida, United States

Unnamed facility

Tupelo, Mississippi, United States

Outcomes

Primary Outcomes

Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12

The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.

Time frame: Week 12

Secondary Outcomes

Part 1: Number of Participants With ALP Response at Week 28

Time frame: Week 28

Part 1: Number of Participants With ALP Remission at Week 28

ALP remission is defined as either normalization of ALP (for participants with baseline ALP between 1.67\*and 2.8\* upper limit of normal \[ULN\] or an ALP less than \[˂\]1.67\*ULN \[for participants with baseline ALP greater than {˃} 2.8\* ULN\]). ALP levels above 1.67\* ULN level were associated with an increased rate of disease progression.

Time frame: Week 28

Part 1: Percent Change From Baseline in ALP Concentration at Week 28

Time frame: Baseline and Week 28

Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28

Time frame: Baseline and Week 28

Data from ClinicalTrials.gov

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