Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

NCT ID: NCT00364819

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2009-12-31

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.

Conditions

Primary Biliary Cirrhosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

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

Group Type: EXPERIMENTAL

rituximab

Intervention Type: DRUG

rituximab 1000 mg IV day 1 and 15, given over 5 - 6 hours

Interventions

rituximab

rituximab 1000 mg IV day 1 and 15, given over 5 - 6 hours

Intervention Type: DRUG

Other Intervention Names

Rituxan (R)

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Merrill Eric Gershwin, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

M. Eric Gershwin, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Christopher L Bowlus, MD

Role: STUDY_DIRECTOR

University of California, Davis

Locations

University of California Davis Medical Center

Sacramento, California, United States

Countries

United States

Related Links

http://www.liverfoundation.org

American Liver Foundation

http://www.pbcers.org

Primary Biliary Cirrhosis Organization

Other Identifiers

200614025

Identifier Type: -

Identifier Source: org_study_id