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

Phase 2

Completed

• Conditions: Primary Biliary Cirrhosis
• Interventions: Drug: ustekinumab 45 mg; Drug: ustekinumab 90 mg; Drug: Placebo; Drug: ustekinumab 180 mg

• Registration Number: NCT01389973
• Lead Sponsor: Janssen Research & Development, LLC

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.

Study Timeline

• Study First Submitted: 2011-07-07
• Study First Submitted QC: 2011-07-07
• Study First Posted: 2011-07-08
• Study Start: 2011-09
• Disposition First Submitted: 2013-05-22
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Disposition First Submitted QC: 2013-09-09
• Disposition First Posted: 2013-09-17
• Results First Submitted: 2014-08-19
• Results First Submitted QC: 2014-10-14
• Results First Posted: 2014-10-15
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-17
• Last Update Posted: 2016-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double-blind: ustekinumab 45 mg	ustekinumab 45 mg	-
Double-blind: ustekinumab 90 mg	ustekinumab 90 mg	-
Double-blind: placebo	Placebo	-
Open-label: ustekinumab 90 mg	ustekinumab 90 mg	-
Double-blind: ustekinumb 180 mg	ustekinumab 180 mg	-

Primary Outcome Measures

Name	Time	Method
Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12	Week 12	The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.

Secondary Outcome Measures

Name	Time	Method
Part 1: Number of Participants With ALP Response at Week 28	Week 28
Part 1: Percent Change From Baseline in ALP Concentration at Week 28	Baseline and Week 28
Part 1: Number of Participants With ALP Remission at Week 28	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.
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28	Baseline and Week 28