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Initial Study of Rituximab to Treat Primary Biliary Cirrhosis

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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:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Merrill Eric Gershwin, MD, University of California, Davis

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
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


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)




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



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00364819


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

Additional Information:
Responsible Party: Merrill Eric Gershwin, MD, Principal Investigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT00364819     History of Changes
Other Study ID Numbers: 200614025
First Posted: August 16, 2006    Key Record Dates
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:
Fibrosis
Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents