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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01389973
First received: July 7, 2011
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Primary Biliary Cirrhosis
Drug: ustekinumab 90 mg
Drug: ustekinumab 45 mg
Drug: ustekinumab 180 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Greater than 40% decrease from baseline in alkaline phosphatase [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Modified Corpechot Response [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  • Change from baseline in Enhanced Liver Fibrosis (ELF) score [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  • Change form baseline in the modified histologic activity index (HAI), in patients with biopsies [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  • Change from baseline in the total serum bile acid concentrations [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: September 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01389973

Locations
United States, California
Sacramento, California, United States
United States, Florida
Jacksonville, Florida, United States
Miami, Florida, United States
Naples, Florida, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, Mississippi
Tupelo, Mississippi, United States
United States, New York
New York, New York, United States
United States, Tennessee
Chattanooga, Tennessee, United States
Germantown, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Washington
Seattle, Washington, United States
Canada, Alberta
Calgary, Alberta, Canada
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

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01389973     History of Changes
Other Study ID Numbers: CR018748, CNTO1275PBC2001, 2011-000554-31
Study First Received: July 7, 2011
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

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, Biliary
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014