Clinical trial NCT00364819: Initial Study of Rituximab to Treat Primary Biliary Cirrhosis
Official title: Effects of Rituximab (Rituxan) on B Cell and AMA Response in Patients With Primary Biliary Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Primary Biliary Cirrhosis
Keywords: Primary Biliary Cirrhosis
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2006-08-16
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 52 weeks
Secondary outcomes:
measure: Change in Serum Immunoglobulin G
timeFrame: 52 Weeks
measure: Change in Serum Immunoglobulin A
timeFrame: 52 Weeks
measure: Change in Serum Immunoglobulin M
timeFrame: 52 Weeks
measure: Change in Serum Alkaline Phosphatase
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: M. Eric Gershwin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Christopher L Bowlus, MD
role: STUDY_DIRECTOR
References: