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

A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy and Safety of Ustekinumab in Subjects With Primary Biliary Cirrhosis Who Had an Inadequate Response to Ursodeoxycholic Acid (UDCA)

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.

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: ustekinumab 90 mg; Drug: ustekinumab 45 mg; Drug: ustekinumab 180 mg; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• United States
  • Florida
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
    • Naples, Florida, United States
  • Mississippi
    • Tupelo, Mississippi, United States
  • New York
    • New York, New York, United States
  • Texas
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open-label: ustekinumab 90 mg	Drug: 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.
EXPERIMENTAL: Double-blind: ustekinumab 45 mg	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.
EXPERIMENTAL: Double-blind: ustekinumab 90 mg	Drug: 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.
EXPERIMENTAL: Double-blind: ustekinumb 180 mg	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.
PLACEBO_COMPARATOR: Double-blind: placebo	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With ALP Response at Week 28		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.	Week 28
Part 1: Percent Change From Baseline in ALP Concentration at Week 28		Baseline and Week 28
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28		Baseline and Week 28

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 7, 2011
• First Posted (ESTIMATE): July 8, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): June 20, 2016
• Last Update Submitted That Met QC Criteria: June 17, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: ustekinumab; primary biliary cirrhosis; STELARA; ursodeoxycholic acid (UDCA); Diseases [C] - Digestive System Diseases [C06]
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR018748; CNTO1275PBC2001 (OTHER: Janssen Research & Development, LLC); 2011-000554-31 (EUDRACT_NUMBER)