Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

Phase 1

Completed

Conditions: Primary Biliary Cirrhosis

Interventions: Drug: rituximab

Registration Number: NCT00364819

Lead Sponsor: University of California, Davis

Brief Summary: The purpose of this study is to determine the safety of the anti-CD20 antibody rituximab in treating patients with Primary Biliary Cirrhosis (PBC). Rituximab is a laboratory-made antibody currently used to treat some kinds of lymphoma. Rituximab may also help people with PBC, a disease of the immune system. However, the safety of rituximab in PBC patients must first be established.

Detailed Description: This is a pilot, open-label, study on 10 female patients with AMA-positive PBC to determine the effects of two infusions of rituximab on response of memory B cells to bacterial motifs, on biochemical function, and histological features. We will enroll 10 consecutive AMA-positive patients with the diagnosis of PBC based on internationally accepted criteria and histological staging determined at liver biopsy and being currently treated with UDCA. Importantly, patients with advanced histological stages, decompensated liver disease, or waiting for OLT will not be included in the study (see exclusion criteria).

Patients eligible and willing to enter the study will be evaluated at baseline by isolation and study of frequency and absolute numbers of B cells and their function, biochemical and AMA tests. Histology and quality of life will be also evaluated in all patients. The methodology to be used for B cell study is already well-established in our laboratory as can be seen in the attached paper (Kikuchi et al. 2005b). Patients will be administered 1,000 mg rituximab intravenously by slow infusion on Day 1 and Day 15 (+/- 1 day). Rituximab's pharmacokinetics indicate that complete B cell depletion is obtained 2-3 days after administration and that such effect may be lost after 9 months (Vieira et al. 2004). In addition to our B cell work, serum samples will undergo AMA testing, including titers, using recombinant mitochondrial antigens (Miyakawa et al. 2001). Patients will also undergo serum chemistry panel, which includes liver function tests. Patients will continue on a steady dose of UDCA therapy throughout the study.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 6

Inclusion Criteria

Liver biopsy showing histological PBC stages I, II, or III
Presence of all criteria for the diagnosis of PBC
serum AMA at titer >1:40
alkaline phosphatase >2X normal value for >6 months
compatible liver histology
Incomplete response to UDCA after 6 months of treatment.
Negative pregnancy test (female patients in fertile age)
Adequate renal function (serum creatinine < 1.2)

Exclusion Criteria

End-stage/decompensated liver disease
ascites
jaundice with serum bilirubin > 2mg/dl
history of digestive bleeding secondary to portal hypertension or endoscopic evidence of varices at stage F2
history of hepatic encephalopathy
INR>1.2
Other coexisting causes of liver disease
Use of other immunosuppressive medications 4 weeks prior to enrollment
Diuretics use

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	rituximab	rituximab 1000 mg IV on days 1 and 15, given over 5 - 6 hours

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	52 weeks

Secondary Outcome Measures

Name	Time	Method
Change in Serum Immunoglobulin A	52 Weeks	The difference in serum immunoglobulin A from Baseline to Week 52
Change in Serum Immunoglobulin M	52 Weeks	The difference in serum immunoglobulin M from Baseline to Week 52
Change in Serum Alkaline Phosphatase	52 Weeks	The difference in serum alkaline phosphatase from Baseline to Week 52
Change in Serum Immunoglobulin G	52 Weeks	The difference in serum immunoglobulin G from Baseline to Week 52