Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Biological: abatacept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abatacept 125 mg weekly<br>Open label treatment with Abatacept | Biological: abatacept<br>* 125 mg subcutaneously each week for 24 weeks<br>* Other names: Orencia;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Biliary Cirrhosis, Ursodeoxycholic acid, Abatacept, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)