Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis

Primary Biliary Cirrhosis Clinical Trial

— PBC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02078882
• Other study ID #: 599969
• Secondary ID: IM101-457
• Status: Completed
• Phase: Phase 4
• Start date: September 2014
• Est. completion date: October 2018

Study information

• Verified date: March 2020
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

Biological:
• abatacept
125 mg subcutaneously each week for 24 weeks

Locations

Country	Name	City	State
United States	Univeristy of California Davis Medical Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
Christopher Bowlus, MD	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunoglobulin M (IgM) Levels	Change in IgM level from Day 0 to Week 24	Week 24
Other	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
Other	Abatacept Levels	Trough serum levels of abatacept	Day 0 and Weeks 4, 12, 24, and 36
Primary	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	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
Secondary	Absolute Change in Alkaline Phosphatase	The absolute change in alkaline phosphatase from Day 0 to Week 24.	Week 24
Secondary	Absolute Change in Alanine Transferase (ALT)	The absolute change in alanine transferase (ALT) from Day 0 to Week 24.	Week 24
Secondary	Liver Stiffness Measured by Magnetic Resonance Elastography	Change in liver stiffness measured by magnetic resonance elastography from Day 0 to Week 24.	Week 24
Secondary	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
Secondary	Percent Change in Alkaline Phosphatase	The percent change in alkaline phosphatase from Day 0 to Week 24.	Week 24
Secondary	Percent Change in Alanine Transferase (ALT)	The percent change in alanine transferase (ALT) from Day 0 to Week 24.	Week 24

External Links

•   PBC Patient Organization