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Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis

Primary Purpose

Hepatitis C, Vasculitis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring Hepatitis, Vasculitis, Rituximab, Cryoglobulinemia, Hepatitis C, HcV-cV, Cryoglobulinemic Vasculitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: Diagnosis of HCV-CV: must have all of the following HCV infection documented by serology and/or plasma HCV RNA. One or more organ system with objective evidence of active vasculitis such as: Palpable purpura; Glomerulonephritis (defined by the presence of glomerular hematuria and/or new or worsening proteinuria); Acute peripheral neuropathy. Detectable cryoglobulins and/or RF. Failure of treatment with IFN-alpha and ribavirin to control manifestations of HCV-CV OR intolerance to IFN-alpha/ribavirin regimen. Patients must have a personal physician responsible for the care of their HCV. Ages of 18 and 75 years Willingness to use effective contraception during and for 12 months following Rituximab treatment. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception. EXCLUSION CRITERIA: Recent (within 4 weeks) initiation of or increase in immunosuppressive therapy. Active systemic infection (other than hepatitis C). Pregnancy or breast feeding. Prior treatment with Rituximab. Known allergy to murine proteins. Significant renal insufficiency (creatinine clearance less than 30 ml/min). Presence of life-threatening HCV-CV; defined as rapidly progressive glomerulonephritis (defined as a doubling of the serum creatinine over a 3 month period), CNS vasculitis, cardiac disease due to active vasculitis, or GI vasculitis (defined by ischemic bowel, perforation, or infarction). Significant hepatic insufficiency as manifested by Child-Pugh classification of B or C. History of variceal bleeding, encephalopathy. History of liver transplantation. Co-infection with either HBV or HIV. Any underlying medical condition that in the judgment of the investigator would put the patient at increased risk for serious infusion-related adverse events.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Immediate treatment

Delayed treatment

Arm Description

Patients receive treatment with four weekly infusions of rituximab 375mg/m2 immediately following randomization.

Patients treated with standard therapy (corticosteroids, plasma exchange, etc.). After 6 months, they are eligibile to cross over and receive four weekly infusions of rituximab.

Outcomes

Primary Outcome Measures

Percent of Patients in Remission
The primary endpoint was the difference in rate of remission between the 2 arms at 6 months from study entry.

Secondary Outcome Measures

Full Information

First Posted
January 5, 2002
Last Updated
April 10, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00029107
Brief Title
Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis
Official Title
Rituximab (Anti-CD20) for the Treatment of Hepatitis C Associated Cryoglobulinemic Vasculitis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
December 2001 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to assess the efficacy of Rituximab (anti-CD20) in the treatment of patients with hepatitis C associated cryoglobulinemic vasculitis (HCV-CV) who have failed or are intolerant to interferon-alpha/ribavirin therapy. Up to 75 patients may be screened to enroll 34 adult patients with active HCV-CV in this randomized, non-blinded phase I/II trial. Patients will be randomized to receive either Rituximab 375 mg/M(2) on days 1, 8, 15 and 22 beginning at the time of enrollment or standard therapy. Patients in both groups will be maintained on stable doses of any immunosuppressive therapies that they were receiving at the time of enrollment. Response to Rituximab will be assessed by clinical and laboratory parameters. Although the cause of cryoglobulinemic vasculitis is not known, a critical component is the presence of cryoglobulins-abnormal proteins that white blood cells called B lymphocytes produce in response to the chronic hepatitis C infection. Rituximab decreases the number of B cells. The Food and Drug Administration approved Rituximab in 1997 for the treatment of B-cell non-Hodgkin's lymphoma. Patients between 18 and 75 years of age with hepatitis C and signs and symptoms of cryoglobulinemic vasculitis may be eligible for this study. They must have failed, or been unable to tolerate, treatment with IFN-a and ribavirin. Candidates will be screened with a history and physical examination, electrocardiogram (ECG), blood and urine tests, 24-hour urine collection and chest X-ray, if clinically indicated. Participants will be randomly assigned to receive Rituximab upon entering the study or 6 months after entering the study. Those whose treatment is delayed 6 months will be followed once a month at NIH for disease evaluation and blood tests during that time. Patients will be given Rituximab intravenously (through a vein) once a week for 4 weeks. For the first dose, patients will be admitted to the hospital for at least 24 hours after the infusion for monitoring. Subsequent infusions will be given on an inpatient or outpatient basis, depending on how the infusion is tolerated. The day before each infusion they will have a history and physical examination, blood work, and other tests, such as X-rays, as clinically indicated. After the four infusions, patients will be followed for drug side effects and response to treatment. They will have blood tests every week for 4 weeks and will then return to NIH for 1 day every month for 12 months for a physical examination, blood tests, and X-rays, if medically indicated. Visits may be more frequent, if necessary, and patients may be asked to stay longer than a day if test findings requ...
Detailed Description
Although the cause of cryoglobulinemic vasculitis is not known, a critical component is the presence of cryoglobulins-abnormal proteins that white blood cells called B lymphocytes produce in response to the chronic hepatitis C infection. Rituximab decreases the number of B cells. The Food and Drug Administration approved Rituximab in 1997 for the treatment of B-cell non-Hodgkin's lymphoma. Patients between 18 and 75 years of age with hepatitis C and signs and symptoms of cryoglobulinemic vasculitis may be eligible for this study. They must have failed, or been unable to tolerate, treatment with IFN-a and ribavirin. Candidates will be screened with a history and physical examination, electrocardiogram (ECG), blood and urine tests, 24-hour urine collection and chest X-ray, if clinically indicated. Participants will be randomly assigned to receive Rituximab or standard therapy for 6 months after entering the study. All patients will be followed once a month at NIH for disease evaluation and blood tests during that time. Patients will be given Rituximab 375 mg/m2intravenously once a week for 4 weeks. The day before each infusion they will have a history and physical examination, blood work, and other tests, such as X-rays, as clinically indicated. After the four infusions, patients will be followed for drug side effects and response to treatment. They will have blood tests every week for 4 weeks and will then return to NIH for 1 day every month for 12 months for a physical examination, blood tests, and X-rays, if medically indicated. Visits may be more frequent, if necessary.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Vasculitis
Keywords
Hepatitis, Vasculitis, Rituximab, Cryoglobulinemia, Hepatitis C, HcV-cV, Cryoglobulinemic Vasculitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Immediate treatment
Arm Type
Other
Arm Description
Patients receive treatment with four weekly infusions of rituximab 375mg/m2 immediately following randomization.
Arm Title
Delayed treatment
Arm Type
Other
Arm Description
Patients treated with standard therapy (corticosteroids, plasma exchange, etc.). After 6 months, they are eligibile to cross over and receive four weekly infusions of rituximab.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
anti-CD20 monoclonal antibody
Primary Outcome Measure Information:
Title
Percent of Patients in Remission
Description
The primary endpoint was the difference in rate of remission between the 2 arms at 6 months from study entry.
Time Frame
month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Diagnosis of HCV-CV: must have all of the following HCV infection documented by serology and/or plasma HCV RNA. One or more organ system with objective evidence of active vasculitis such as: Palpable purpura; Glomerulonephritis (defined by the presence of glomerular hematuria and/or new or worsening proteinuria); Acute peripheral neuropathy. Detectable cryoglobulins and/or RF. Failure of treatment with IFN-alpha and ribavirin to control manifestations of HCV-CV OR intolerance to IFN-alpha/ribavirin regimen. Patients must have a personal physician responsible for the care of their HCV. Ages of 18 and 75 years Willingness to use effective contraception during and for 12 months following Rituximab treatment. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception. EXCLUSION CRITERIA: Recent (within 4 weeks) initiation of or increase in immunosuppressive therapy. Active systemic infection (other than hepatitis C). Pregnancy or breast feeding. Prior treatment with Rituximab. Known allergy to murine proteins. Significant renal insufficiency (creatinine clearance less than 30 ml/min). Presence of life-threatening HCV-CV; defined as rapidly progressive glomerulonephritis (defined as a doubling of the serum creatinine over a 3 month period), CNS vasculitis, cardiac disease due to active vasculitis, or GI vasculitis (defined by ischemic bowel, perforation, or infarction). Significant hepatic insufficiency as manifested by Child-Pugh classification of B or C. History of variceal bleeding, encephalopathy. History of liver transplantation. Co-infection with either HBV or HIV. Any underlying medical condition that in the judgment of the investigator would put the patient at increased risk for serious infusion-related adverse events.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael C Sneller, MD
Organizational Affiliation
National Institute of Allergy and Infectious Diseases (NIAID)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
1660716
Citation
Ferri C, Greco F, Longombardo G, Palla P, Moretti A, Marzo E, Fosella PV, Pasero G, Bombardieri S. Antibodies to hepatitis C virus in patients with mixed cryoglobulinemia. Arthritis Rheum. 1991 Dec;34(12):1606-10. doi: 10.1002/art.1780341221.
Results Reference
background
PubMed Identifier
1326246
Citation
Misiani R, Bellavita P, Fenili D, Borelli G, Marchesi D, Massazza M, Vendramin G, Comotti B, Tanzi E, Scudeller G, et al. Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med. 1992 Oct 1;117(7):573-7. doi: 10.7326/0003-4819-117-7-573.
Results Reference
background
PubMed Identifier
7509124
Citation
Cacoub P, Fabiani FL, Musset L, Perrin M, Frangeul L, Leger JM, Huraux JM, Piette JC, Godeau P. Mixed cryoglobulinemia and hepatitis C virus. Am J Med. 1994 Feb;96(2):124-32. doi: 10.1016/0002-9343(94)90132-5.
Results Reference
background
PubMed Identifier
22147444
Citation
Sneller MC, Hu Z, Langford CA. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. Arthritis Rheum. 2012 Mar;64(3):835-42. doi: 10.1002/art.34322.
Results Reference
derived

Learn more about this trial

Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis

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