Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

• ClinicalTrials.gov Identifier: NCT00364819
• Recruitment Status: Completed
• First Posted: August 16, 2006
• Results First Posted: June 1, 2017
• Last Update Posted: July 2, 2017
• Sponsor: University of California, Davis
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Merrill Eric Gershwin, MD, University of California, Davis

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.

Condition or disease	Intervention/treatment	Phase
Primary Biliary Cirrhosis	Drug: rituximab	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Rituximab (Rituxan) on B Cell and AMA Response in Patients With Primary Biliary Cirrhosis
• Study Start Date: January 2007
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

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 Name: Rituxan (R)

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: 52 weeks ]

Secondary Outcome Measures :

1. Change in Serum Immunoglobulin G [ Time Frame: 52 Weeks ]
   The difference in serum immunoglobulin G from Baseline to Week 52
2. Change in Serum Immunoglobulin A [ Time Frame: 52 Weeks ]
   The difference in serum immunoglobulin A from Baseline to Week 52
3. Change in Serum Immunoglobulin M [ Time Frame: 52 Weeks ]
   The difference in serum immunoglobulin M from Baseline to Week 52
4. Change in Serum Alkaline Phosphatase [ Time Frame: 52 Weeks ]
   The difference in serum alkaline phosphatase from Baseline to Week 52

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

University of California Davis Medical Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Genentech, Inc.

Investigators

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

More Information

Additional Information:

American Liver Foundation 

Primary Biliary Cirrhosis Organization 

• Responsible Party: Merrill Eric Gershwin, MD, Principal Investigator, University of California, Davis
• ClinicalTrials.gov Identifier: NCT00364819
• Other Study ID Numbers: 200614025
• First Posted: August 16, 2006
• Results First Posted: June 1, 2017
• Last Update Posted: July 2, 2017
• Last Verified: June 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

Keywords provided by Merrill Eric Gershwin, MD, University of California, Davis:

Primary Biliary Cirrhosis

Additional relevant MeSH terms:

Liver Cirrhosis; Liver Cirrhosis, Biliary; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases; Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents