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

• ClinicalTrials.gov Identifier: NCT01389973
• Recruitment Status: Completed
• First Posted: July 8, 2011
• Results First Posted: October 15, 2014
• Last Update Posted: June 20, 2016
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Primary Biliary Cirrhosis	Drug: ustekinumab 90 mg; Drug: ustekinumab 45 mg; Drug: ustekinumab 180 mg; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: September 2011
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

1. Part 1: Number of Participants With ALP Response at Week 28 [ Time Frame: Week 28 ]
2. Part 1: Number of Participants With ALP Remission at Week 28 [ Time Frame: 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.
3. Part 1: Percent Change From Baseline in ALP Concentration at Week 28 [ Time Frame: Baseline and Week 28 ]
4. Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28 [ Time Frame: Baseline and Week 28 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Jacksonville, Florida, United States

Miami, Florida, United States

Naples, Florida, United States

United States, Mississippi

Tupelo, Mississippi, United States

United States, New York

New York, New York, United States

United States, Texas

Houston, Texas, United States

Canada, British Columbia

Vancouver, British Columbia, Canada

Canada, Nova Scotia

Halifax, Nova Scotia, Canada

Canada, Ontario

Toronto, Ontario, Canada

Canada, Quebec

Montreal, Quebec, Canada

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Review.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01389973
• Other Study ID Numbers: CR018748; CNTO1275PBC2001 ( Other Identifier: Janssen Research & Development, LLC ); 2011-000554-31 ( EudraCT Number )
• First Posted: July 8, 2011
• Results First Posted: October 15, 2014
• Last Update Posted: June 20, 2016
• Last Verified: June 2016

Keywords provided by Janssen Research & Development, LLC:

Diseases [C] - Digestive System Diseases [C06]; primary biliary cirrhosis; ursodeoxycholic acid (UDCA); STELARA; ustekinumab

Additional relevant MeSH terms:

Liver Cirrhosis; Liver Cirrhosis, Biliary; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases; Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Ustekinumab; Dermatologic Agents