Hepatitis CPhase 2NCT00029107
Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis
A Phase 2 study testing Rituximab in people with Hepatitis C and Vasculitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatitis C, Vasculitis
- 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
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2001to May 2011
- Phase
- Phase 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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).
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Rituximab (Anti-CD20) for the Treatment of Hepatitis C Associated Cryoglobulinemic Vasculitis
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.
Read more
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...
Read the 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.
- Conditions
- Hepatitis C, Vasculitis
- Being tested
- Rituximab
- Keywords
- Hepatitis, Vasculitis, Rituximab, Cryoglobulinemia, Hepatitis C, HcV-cV, Cryoglobulinemic Vasculitis
- Medical subject headings
- Hepatitis C, Vasculitis, Hepatitis, Cryoglobulinemia, Cryoglobulinemia, Familial Mixed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
anti-CD20 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Immediate treatment | Other | Patients receive treatment with four weekly infusions of rituximab 375mg/m2 immediately following randomization. Receives: Drug: Rituximab |
| Delayed treatment | Other | 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. Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2002 (estimated)
- Study startDec 2001
- Primary completionMay 2011
- Study completionMay 2011
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Michael C Sneller, MD, National Institutes of Health Clinical Center (CC)
- Investigators
- Michael C Sneller, MD, Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00029107
- Sponsor's protocol ID
- 020096
- Other IDs
- 02-I-0096
- Status last verified
- Apr 2012
- First submitted
- 5 Jan 2002
- Last updated
- 16 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 1660716Misiani 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.
PubMed 1326246Cacoub 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.
PubMed 7509124Sneller 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.
PubMed 22147444
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab (Anti-CD20) for the Treatment of Hepatitis C Associated Cryoglobulinemic Vasculitis
- ClinicalTrials.gov ID
- NCT00029107
- Acronym / sponsor ID
- 020096
- Conditions
- Hepatitis C, Vasculitis
- Keywords
- Hepatitis, Vasculitis, Rituximab, Cryoglobulinemia, Hepatitis C, HcV-cV, Cryoglobulinemic Vasculitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Dec 2001
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 7 Jan 2002 (estimated)
- Results
- Posted 3 Apr 2012
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate treatment | Other | Drug: RituximabPatients receive treatment with four weekly infusions of rituximab 375mg/m2 immediately following randomization. |
| Delayed treatment | Other | Drug: RituximabPatients treated with standard therapy (corticosteroids, plasma exchange, etc.). After 6 months, they are eligibile to cross over and receive four weekly infusions of rituximab. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosis of HCV-CV: must have all of the following
- HCV infection documented by serology and/or plasma HCV RNA.
- Palpable purpura;
- Glomerulonephritis (defined by the presence of glomerular hematuria and/or new or worsening proteinuria);
- Acute peripheral neuropathy.
Key exclusion criteria (12 listed)
- 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.
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 |
|---|---|---|
| Rituximabanti-CD20 monoclonal antibody | Drug | Delayed treatment, Immediate treatment |
Primary outcome
Percent of Patients in Remission
Time frame: month 6
The primary endpoint was the difference in rate of remission between the 2 arms at 6 months from study entry.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1660716Ferri 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.
- Background: PubMed 1326246Misiani 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.
- Background: PubMed 7509124Cacoub 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.
- Derived from this study: PubMed 22147444Sneller 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.
Related trials for Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
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.
Michael C Sneller, MD principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Hepatitis C and Vasculitis, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 11 inclusion and 12 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 16 Apr 2012. 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 phase mean?
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 3 Apr 2012). 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?
Percent of Patients in Remission (time frame: month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00029107, which also lists 4 linked publications.
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 16 Apr 2012.