Primary Biliary CirrhosisPhase 1/2NCT00364819
Initial Study of Rituximab to Treat Primary Biliary Cirrhosis
A Phase 1/2 study testing rituximab in people with Primary Biliary Cirrhosis, run by University of California, Davis at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Dec 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- Other coexisting causes of liver disease
- Use of other immunosuppressive medications 4 weeks prior to enrollment
- Diuretics use
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Medical Center
Sacramento, California, 95817
About this study
Official title: 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.
Read the 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.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- rituximab
- Keywords
- Primary Biliary Cirrhosis
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabDrug
Also called Rituxan (R)
rituximab 1000 mg IV day 1 and 15, given over 5 - 6 hours
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | rituximab 1000 mg IV on days 1 and 15, given over 5 - 6 hours Receives: Drug: rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Measured: 52 weeks
Secondary outcomes (4)
Change in Serum Immunoglobulin G
The difference in serum immunoglobulin G from Baseline to Week 52
Measured: 52 Weeks
Change in Serum Immunoglobulin A
The difference in serum immunoglobulin A from Baseline to Week 52
Measured: 52 Weeks
Change in Serum Immunoglobulin M
The difference in serum immunoglobulin M from Baseline to Week 52
Measured: 52 Weeks
Change in Serum Alkaline Phosphatase
The difference in serum alkaline phosphatase from Baseline to Week 52
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2006 (estimated)
- Study startJan 2007
- Primary completionJul 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Merrill Eric Gershwin, MD, University of California, Davis
- Investigators
- M. Eric Gershwin, MD, Principal investigator, University of California, DavisChristopher L Bowlus, MD, Study director, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00364819
- Sponsor's protocol ID
- 200614025
- Status last verified
- Jun 2017
- First submitted
- 15 Aug 2006
- Last updated
- 2 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Rituximab (Rituxan) on B Cell and AMA Response in Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT00364819
- Acronym / sponsor ID
- 200614025
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- Primary Biliary Cirrhosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jan 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 16 Aug 2006 (estimated)
- Results
- Posted 1 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rituximabrituximab 1000 mg IV on days 1 and 15, given over 5 - 6 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabAlso: Rituxan (R)rituximab 1000 mg IV day 1 and 15, given over 5 - 6 hours | Drug | 1 |
Primary outcome
Number of Participants With Adverse Events
Time frame: 52 weeks
4 secondary outcomes
Change in Serum Immunoglobulin G
Time frame: 52 Weeks
Change in Serum Immunoglobulin A
Time frame: 52 Weeks
Change in Serum Immunoglobulin M
Time frame: 52 Weeks
Change in Serum Alkaline Phosphatase
Time frame: 52 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- American Liver FoundationLink provided by the sponsor.
- Primary Biliary Cirrhosis OrganizationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M. Eric Gershwin, MD principal investigator
University of California, Davis
Christopher L Bowlus, MD study director
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rituximab in people with Primary Biliary Cirrhosis, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.