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

Primary Purpose

Primary Biliary Cirrhosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ustekinumab 90 mg
ustekinumab 45 mg
ustekinumab 180 mg
Placebo
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring Diseases [C] - Digestive System Diseases [C06], primary biliary cirrhosis, ursodeoxycholic acid (UDCA), STELARA, ustekinumab

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Open-label: ustekinumab 90 mg

Double-blind: ustekinumab 45 mg

Double-blind: ustekinumab 90 mg

Double-blind: ustekinumb 180 mg

Double-blind: placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
July 7, 2011
Last Updated
June 17, 2016
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01389973
Brief Title
A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid
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 Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cirrhosis
Keywords
Diseases [C] - Digestive System Diseases [C06], primary biliary cirrhosis, ursodeoxycholic acid (UDCA), STELARA, ustekinumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-label: ustekinumab 90 mg
Arm Type
Experimental
Arm Title
Double-blind: ustekinumab 45 mg
Arm Type
Experimental
Arm Title
Double-blind: ustekinumab 90 mg
Arm Type
Experimental
Arm Title
Double-blind: ustekinumb 180 mg
Arm Type
Experimental
Arm Title
Double-blind: placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ustekinumab 90 mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
ustekinumab 45 mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
ustekinumab 180 mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12
Description
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 Outcome Measure Information:
Title
Part 1: Number of Participants With ALP Response at Week 28
Time Frame
Week 28
Title
Part 1: Number of Participants With ALP Remission at Week 28
Description
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
Title
Part 1: Percent Change From Baseline in ALP Concentration at Week 28
Time Frame
Baseline and Week 28
Title
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28
Time Frame
Baseline and Week 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Jacksonville
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Naples
State/Province
Florida
Country
United States
City
Tupelo
State/Province
Mississippi
Country
United States
City
New York
State/Province
New York
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Halifax
State/Province
Nova Scotia
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
25543678
Citation
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.
Results Reference
derived

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

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