Clinical trial NCT02078882: Study of Abatacept (Orencia) to Treat Primary Biliary Cirrhosis
Official title: Abatacept For The Treatment Of Primary Biliary Cirrhosis With An Incomplete Biochemical Response To Ursodeoxycholic Acid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Biliary Cirrhosis
Keywords: Primary Biliary Cirrhosis
Ursodeoxycholic acid
Abatacept
Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2014-03-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Biochemical Response
timeFrame: Week 24
Secondary outcomes:
measure: Drug Safety
timeFrame: Weeks 2, 4, 12, 24, and 36
measure: Absolute Change in Alkaline Phosphatase
timeFrame: Week 24
measure: Absolute Change in Alanine Transferase (ALT)
timeFrame: Week 24
measure: Liver Stiffness Measured by Magnetic Resonance Elastography
timeFrame: Week 24
measure: Primary Billiary Cholangitis Quality of Life
timeFrame: Week 24
measure: Percent Change in Alkaline Phosphatase
timeFrame: Week 24
measure: Percent Change in Alanine Transferase (ALT)
timeFrame: Week 24
Other outcomes:
measure: Immunoglobulin M (IgM) Levels
timeFrame: Week 24
measure: Memory T Cell Frequencies
timeFrame: Week 24
measure: Abatacept Levels
timeFrame: Day 0 and Weeks 4, 12, 24, and 36
Locations:
city: Sacramento
country: United States
facility: Univeristy of California Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: Christopher L Bowlus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: M. Eric Gershwin, MD
role: PRINCIPAL_INVESTIGATOR
References: