Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

Effects of Rituximab (Rituxan) on B Cell and AMA Response in Patients With Primary Biliary Cirrhosis

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.

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; rituximab 1000 mg IV on days 1 and 15, given over 5 - 6 hours	Drug: rituximab; rituximab 1000 mg IV day 1 and 15, given over 5 - 6 hours; Other Names: Rituxan (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Immunoglobulin G	The difference in serum immunoglobulin G from Baseline to Week 52	52 Weeks
Change in Serum Immunoglobulin A	The difference in serum immunoglobulin A from Baseline to Week 52	52 Weeks
Change in Serum Immunoglobulin M	The difference in serum immunoglobulin M from Baseline to Week 52	52 Weeks
Change in Serum Alkaline Phosphatase	The difference in serum alkaline phosphatase from Baseline to Week 52	52 Weeks

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: M. Eric Gershwin, MD, University of California, Davis; Study Director: Christopher L Bowlus, MD, University of California, Davis

Publications and helpful links

Helpful Links

• American Liver Foundation
• Primary Biliary Cirrhosis Organization

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: August 15, 2006
• First Submitted That Met QC Criteria: August 15, 2006
• First Posted (Estimate): August 16, 2006

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 5, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Primary Biliary Cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 200614025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD may be shared upon request and appropriate approval from Institutional Review Boards and material transfer agreements. No patient identifiers will be shared. Requests for IPD may be made to the Principle Investigator.