Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis

Phase 4

Completed

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Abatacept 125 mg weekly	abatacept	Open label treatment with Abatacept

Primary Outcome Measures

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

Secondary Outcome Measures

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