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

Abatacept For The Treatment Of Primary Biliary Cirrhosis With An Incomplete Biochemical Response To Ursodeoxycholic Acid

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).

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Biological: abatacept

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • Univeristy of California Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abatacept 125 mg weekly; Open label treatment with Abatacept	Biological: abatacept; 125 mg subcutaneously each week for 24 weeks; Other Names: Orencia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Response	Number of Participants with a decrease of alkaline phosphatase by > 40%of the Day 0 level at 24 weeks of treatment.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Safety	Number of participants with any adverse events, clinically significant changes in vital signs, laboratory test abnormalities, and clinical tolerability of the drug.	Weeks 2, 4, 12, 24, and 36
Absolute Change in Alkaline Phosphatase	The absolute change in alkaline phosphatase from Day 0 to Week 24.	Week 24
Absolute Change in Alanine Transferase (ALT)	The absolute change in alanine transferase (ALT) from Day 0 to Week 24.	Week 24
Liver Stiffness Measured by Magnetic Resonance Elastography	Change in liver stiffness measured by magnetic resonance elastography from Day 0 to Week 24.	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.	Week 24
Percent Change in Alkaline Phosphatase	The percent change in alkaline phosphatase from Day 0 to Week 24.	Week 24
Percent Change in Alanine Transferase (ALT)	The percent change in alanine transferase (ALT) from Day 0 to Week 24.	Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunoglobulin M (IgM) Levels	Change in IgM level from Day 0 to Week 24	Week 24
Memory T Cell Frequencies	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	Week 24
Abatacept Levels	Trough serum levels of abatacept	Day 0 and Weeks 4, 12, 24, and 36

Collaborators and Investigators

• Sponsor: Christopher Bowlus, MD
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: M. Eric Gershwin, MD, University of California, Davis

Publications and helpful links

Helpful Links

• PBC Patient Organization

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: March 3, 2014
• First Posted (Estimate): March 5, 2014

Study Record Updates

• Last Update Posted (Actual): April 9, 2020
• Last Update Submitted That Met QC Criteria: March 28, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Abatacept; Ursodeoxycholic acid; Primary Biliary Cirrhosis; Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: 599969; IM101-457 (Other Identifier: Other)