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Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

Primary Purpose

Primary Biliary Cirrhosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring Primary Biliary Cirrhosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of California Davis Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events

Secondary Outcome Measures

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

Full Information

First Posted
August 15, 2006
Last Updated
June 5, 2017
Sponsor
University of California, Davis
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00364819
Brief Title
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

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Davis
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cirrhosis
Keywords
Primary Biliary Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
rituximab 1000 mg IV on days 1 and 15, given over 5 - 6 hours
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan (R)
Intervention Description
rituximab 1000 mg IV day 1 and 15, given over 5 - 6 hours
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Change in Serum Immunoglobulin G
Description
The difference in serum immunoglobulin G from Baseline to Week 52
Time Frame
52 Weeks
Title
Change in Serum Immunoglobulin A
Description
The difference in serum immunoglobulin A from Baseline to Week 52
Time Frame
52 Weeks
Title
Change in Serum Immunoglobulin M
Description
The difference in serum immunoglobulin M from Baseline to Week 52
Time Frame
52 Weeks
Title
Change in Serum Alkaline Phosphatase
Description
The difference in serum alkaline phosphatase from Baseline to Week 52
Time Frame
52 Weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M. Eric Gershwin, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christopher L Bowlus, MD
Organizational Affiliation
University of California, Davis
Official's Role
Study Director
Facility Information:
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.liverfoundation.org
Description
American Liver Foundation
URL
http://www.pbcers.org
Description
Primary Biliary Cirrhosis Organization

Learn more about this trial

Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

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