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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT02078882
First received: March 3, 2014
Last updated: November 23, 2016
Last verified: November 2016
  Purpose
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).

Condition Intervention Phase
Primary Biliary Cirrhosis
Biological: abatacept
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Abatacept For The Treatment Of Primary Biliary Cirrhosis With An Incomplete Biochemical Response To Ursodeoxycholic Acid

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Biochemical Response [ Time Frame: Week 24 ]
    Normalization of alkaline phosphatase or decrease of alkaline phosphatase by > 40% of the Day 0 level at 24 weeks of treatment.


Secondary Outcome Measures:
  • Safety [ Time Frame: Weeks 2, 4, 12, 24, and 36 ]
    Safety outcomes include adverse events, clinically significant changes in vital signs, laboratory test abnormalities, and clinical tolerability of the drug.

  • Absolute and percent change in alkaline phosphatase [ Time Frame: Week 24 ]
    The absolute and percent change in alkaline phosphatase from Day 0 to Week 24.

  • Absolute and percent change in alanine transferase (ALT) [ Time Frame: Week 24 ]
    The absolute and percent change in alanine transferase (ALT) from Day 0 to Week 24.

  • Liver stiffness measured by magnetic resonance elastography [ Time Frame: Week 24 ]
    Change in liver stiffness measured by magnetic resonance elastography from Day 0 to Week 24.

  • Quality of life [ Time Frame: Week 24 ]
    Change in quality of life measured by change in PBC-40 from Day 0 to Week 24.

  • Anti-abatacept titers [ Time Frame: Week 24 ]
    Frequency and titer of anti-abatacept antibody at Day 0 and Week 24

  • Abatacept levels [ Time Frame: Weeks 0, 4, 12, 24, and 36 ]
    Trough levels of abatacept at Day 0 and Weeks 4, 12, 24, and 36.


Other Outcome Measures:
  • Anti-mitochondrial antibody titers [ Time Frame: Week 24 ]
    Change in anti-mitochondrial antibody titers form Day 0 to Week 24.

  • Immunoglobulin M (IgM) Levels [ Time Frame: Week 24 ]
    Change in IgM level from Day 0 to Week 24

  • Memory T cell frequencies [ Time Frame: Week 24 ]
    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


Estimated Enrollment: 20
Study Start Date: September 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abatacept 125 mg weekly
Open label treatment with Abatacept
Biological: abatacept
125 mg subcutaneously each week for 24 weeks
Other Name: Orencia

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
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT02078882

Locations
United States, California
Univeristy of California Davis Medical Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Bristol-Myers Squibb
Investigators
Principal Investigator: Christopher L Bowlus, MD University of California, Davis
Principal Investigator: M. Eric Gershwin, MD University of California, Davis
  More Information

Additional Information:
Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT02078882     History of Changes
Other Study ID Numbers: IM101-457
Study First Received: March 3, 2014
Last Updated: November 23, 2016

Keywords provided by University of California, Davis:
Primary Biliary Cirrhosis
Ursodeoxycholic acid
Abatacept
Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Ursodeoxycholic Acid
Abatacept
Cholagogues and Choleretics
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on March 28, 2017