Rituximab to Treat Hepatitis C-Associated Cryoglobulinemic Vasculitis

NCT00029107 | Completed Phase 2 Results

• 2 other identifiers: 02009602-I-0096
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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...

Conditions

Hepatitis C; Vasculitis

Keywords

Hepatitis; Vasculitis; Rituximab; Cryoglobulinemia; Hepatitis C; HcV-cV; Cryoglobulinemic Vasculitis

Outcome Measures

Primary Outcomes (1)

• 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.

  month 6

Study Arms (2)

Immediate treatment

OTHER

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

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.

Drug: Rituximab

Interventions

Rituximab DRUG

anti-CD20 monoclonal antibody

Delayed treatment; Immediate treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 1660716 BACKGROUND

• 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.

  PMID: 1326246 BACKGROUND

• 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.

  PMID: 7509124 BACKGROUND

• 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.

  PMID: 22147444 DERIVED

MeSH Terms

Conditions

Hepatitis C; Vasculitis; Hepatitis; Cryoglobulinemia; Cryoglobulinemia, Familial Mixed

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was not blinded. In addition, the study was limited to patients who had failed antiviral therapy.

Results Point of Contact

• Title: Michael C Sneller, MD
• Organization: NIAID/NIH

msneller@niaid.nih.gov

301-496-0491

Study Officials

• Michael C Sneller, MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Officer

Study Record Dates

• First Submitted: January 5, 2002
• First Posted: January 7, 2002
• Study Start: December 1, 2001
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: April 16, 2012
• Results First Posted: April 3, 2012

Record last verified: 2012-04

Locations

US (1)