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Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis (PBC)

Primary Purpose

Primary Biliary Cirrhosis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
abatacept
Sponsored by
Christopher Bowlus, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring Primary Biliary Cirrhosis, Ursodeoxycholic acid, Abatacept, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)

Eligibility Criteria

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

Inclusion Criteria:

  • Confirmed PBC diagnosis based upon at least 2 of 3 criteria

    1. Anti-mitochondrial antibody (AMA) titer > 1:40
    2. Alkaline phosphatase > 1.5 times the upper limit of normal for at least 6 months
    3. Liver biopsy findings consistent with PBC
  • Incomplete response to UDCA defined by an alkaline phosphatase > 1.67 X the upper limit of normal after 6 months of UDCA at a minimum dose of 13 mg/kg/d
  • Taking a stable dose of UDCA for at least 3 months prior to Day 0
  • aspartate aminotransferase (AST) and alanine aminotransferase ALT < 5 times the upper limit of normal

Exclusion Criteria:

  • Presence of concomitant liver diseases including viral hepatitis, primary sclerosing cholangitis, alcoholic liver disease, Wilson's disease, hemochromatosis, or Gilbert's syndrome.
  • Prior liver transplantation
  • Decompensated liver disease
  • Use of immunosuppressants within 6 months of Day 0
  • Use of biologic agents within 12 months of Day 0

Sites / Locations

  • Univeristy of California Davis Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Abatacept 125 mg weekly

Arm Description

Open label treatment with Abatacept

Outcomes

Primary Outcome Measures

Biochemical Response
Number of Participants with a decrease of alkaline phosphatase by > 40%of the Day 0 level at 24 weeks of treatment.

Secondary Outcome Measures

Drug Safety
Number of participants with any adverse events, clinically significant changes in vital signs, laboratory test abnormalities, and clinical tolerability of the drug.
Absolute Change in Alkaline Phosphatase
The absolute change in alkaline phosphatase from Day 0 to Week 24.
Absolute Change in Alanine Transferase (ALT)
The absolute change in alanine transferase (ALT) from Day 0 to Week 24.
Liver Stiffness Measured by Magnetic Resonance Elastography
Change in liver stiffness measured by magnetic resonance elastography from Day 0 to Week 24.
Primary Billiary Cholangitis Quality of Life
Change in quality of life measured by change in primary biliary cholangitis (PBC)-40 from Day 0 to Week 24. is a patient-derived, disease specific quality of life measure developed and validated for use in PBC with subscores for domains of symptoms, itch, fatigue, cognition, social, and emotional. Subdomains are summed with a total score range of 36 to 200. Higher scores indicate worse quality of life.
Percent Change in Alkaline Phosphatase
The percent change in alkaline phosphatase from Day 0 to Week 24.
Percent Change in Alanine Transferase (ALT)
The percent change in alanine transferase (ALT) from Day 0 to Week 24.

Full Information

First Posted
March 3, 2014
Last Updated
March 28, 2020
Sponsor
Christopher Bowlus, MD
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02078882
Brief Title
Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis
Acronym
PBC
Official Title
Abatacept For The Treatment Of Primary Biliary Cirrhosis With An Incomplete Biochemical Response To Ursodeoxycholic Acid
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
October 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christopher Bowlus, MD
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if abatacept (Orencia) is effective in patients with primary biliary cirrhosis who do not respond adequately to standard treatment with ursodeoxycholic acid (UDCA, Urso, Ursodiol, Actigall).
Detailed Description
This is an open label, active treatment trial to assess the efficacy and safety of abatacept in subject with PBC who have had an incomplete biochemical response to UDCA. In this trial, 20 subjects with PBC who have had an incomplete biochemical response to UDCA will be assigned to treatment with weekly subcutaneous injections of 125 mg of abatacept. The treatment phase of the study will last 24 weeks with an off-treatment follow up at Week 36. Inclusion criteria include: Confirmed diagnosis of PBC Alkaline phosphatase > 1.67 times the upper limit of normal after 6 months of treatment with UDCA

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cirrhosis
Keywords
Primary Biliary Cirrhosis, Ursodeoxycholic acid, Abatacept, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Abatacept 125 mg weekly
Arm Type
Experimental
Arm Description
Open label treatment with Abatacept
Intervention Type
Biological
Intervention Name(s)
abatacept
Other Intervention Name(s)
Orencia
Intervention Description
125 mg subcutaneously each week for 24 weeks
Primary Outcome Measure Information:
Title
Biochemical Response
Description
Number of Participants with a decrease of alkaline phosphatase by > 40%of the Day 0 level at 24 weeks of treatment.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Drug Safety
Description
Number of participants with any adverse events, clinically significant changes in vital signs, laboratory test abnormalities, and clinical tolerability of the drug.
Time Frame
Weeks 2, 4, 12, 24, and 36
Title
Absolute Change in Alkaline Phosphatase
Description
The absolute change in alkaline phosphatase from Day 0 to Week 24.
Time Frame
Week 24
Title
Absolute Change in Alanine Transferase (ALT)
Description
The absolute change in alanine transferase (ALT) from Day 0 to Week 24.
Time Frame
Week 24
Title
Liver Stiffness Measured by Magnetic Resonance Elastography
Description
Change in liver stiffness measured by magnetic resonance elastography from Day 0 to Week 24.
Time Frame
Week 24
Title
Primary Billiary Cholangitis Quality of Life
Description
Change in quality of life measured by change in primary biliary cholangitis (PBC)-40 from Day 0 to Week 24. is a patient-derived, disease specific quality of life measure developed and validated for use in PBC with subscores for domains of symptoms, itch, fatigue, cognition, social, and emotional. Subdomains are summed with a total score range of 36 to 200. Higher scores indicate worse quality of life.
Time Frame
Week 24
Title
Percent Change in Alkaline Phosphatase
Description
The percent change in alkaline phosphatase from Day 0 to Week 24.
Time Frame
Week 24
Title
Percent Change in Alanine Transferase (ALT)
Description
The percent change in alanine transferase (ALT) from Day 0 to Week 24.
Time Frame
Week 24
Other Pre-specified Outcome Measures:
Title
Immunoglobulin M (IgM) Levels
Description
Change in IgM level from Day 0 to Week 24
Time Frame
Week 24
Title
Memory T Cell Frequencies
Description
Change in cluster of differentiation 4 (CD4)+ cluster of differentiation 44 (CD44)+ cluster of differentiation 62 ligand (CD62L)- and cluster of differentiation 8+ CD44+ CD62L- frequencies in peripheral blood mononuclear cells from Day 0 to Week 24
Time Frame
Week 24
Title
Abatacept Levels
Description
Trough serum levels of abatacept
Time Frame
Day 0 and Weeks 4, 12, 24, and 36

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Confirmed PBC diagnosis based upon at least 2 of 3 criteria Anti-mitochondrial antibody (AMA) titer > 1:40 Alkaline phosphatase > 1.5 times the upper limit of normal for at least 6 months Liver biopsy findings consistent with PBC Incomplete response to UDCA defined by an alkaline phosphatase > 1.67 X the upper limit of normal after 6 months of UDCA at a minimum dose of 13 mg/kg/d Taking a stable dose of UDCA for at least 3 months prior to Day 0 aspartate aminotransferase (AST) and alanine aminotransferase ALT < 5 times the upper limit of normal Exclusion Criteria: Presence of concomitant liver diseases including viral hepatitis, primary sclerosing cholangitis, alcoholic liver disease, Wilson's disease, hemochromatosis, or Gilbert's syndrome. Prior liver transplantation Decompensated liver disease Use of immunosuppressants within 6 months of Day 0 Use of biologic agents within 12 months of Day 0
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher L Bowlus, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
M. Eric Gershwin, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Univeristy of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.pbcers.org
Description
PBC Patient Organization

Learn more about this trial

Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis

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