Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

Primary Biliary Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00364819
• Other study ID #: 2006-14025
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 15, 2006
• Last updated: March 4, 2014
• Start date: January 2007
• Est. completion date: December 2009

Study information

• Verified date: March 2014
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

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

Locations

Country	Name	City	State
United States	University of California Davis Medical Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Davis	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of rituximab in PBC patients		January 2010	Yes

External Links

•   American Liver Foundation
•   Primary Biliary Cirrhosis Organization