Rituxan in Churg Strauss Syndrome With Renal Involvement

• ClinicalTrials.gov Identifier: NCT00424749
• Recruitment Status: Terminated
• First Posted: January 22, 2007
• Results First Posted: December 8, 2011
• Last Update Posted: December 8, 2011
• Sponsor: Fernando Fervenza
• Collaborators: Genentech, Inc.; Biogen; National Center for Research Resources (NCRR)
• Information provided by (Responsible Party): Fernando Fervenza, Mayo Clinic

Study Description

Brief Summary:

Churg-Strauss Syndrome (CSS) is a disease characterized by asthma, abnormally high amounts of eosinophils (a type of white blood cell), and blood vessel inflammation. About 25% of CSS patients develop kidney disease. The goal of this pilot study was to evaluate the safety and effectiveness of Rituximab in inducing remission of kidney disease in patients with CSS.

Condition or disease	Intervention/treatment	Phase
Churg-Strauss Syndrome	Drug: Rituximab; Drug: Prednisone	Phase 2

Detailed Description:

Churg-Strauss syndrome (CSS) is a small vessel systemic vasculitis associated with asthma and eosinophilia that causes glomerulonephritis in about 25% of patients. Rituximab is a chimeric anti-CD20 monoclonal antibody that depletes B cells and is effective in numerous autoimmune disease including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The aim of this study was to evaluate the safety and efficacy of Rituximab in inducing remission of renal disease activity in patients with CSS.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study on the Use of Rituximab in the Treatment of Churg- Strauss Syndrome With Renal Involvement
• Study Start Date: June 2007
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rituximab; 375 mg/m^2/week for 4 weeks	Drug: Rituximab; Patients received 4 weekly doses of rituximab 375 mg/m^2.; Other Names: Rituxan; MabThera; Drug: Prednisone; Prednisone 1 mg/kg/day (not to exceed 80 mg/day) for 4 weeks followed by a taper to 0 mg by 6 months; Other Names: Deltasone; Liquid Pred; Meticorten; Orasone; Prednicen-M; Prednicot; Sterapred; Sterapred DS

Outcome Measures

Primary Outcome Measures :

1. Participants With Remission of Renal Disease Activity at 3 Months [ Time Frame: 3 months after beginning of remission induction regimen ]
   Remission of renal disease activity was indicated by stable or falling creatinine, absence of active urinary sediment AND reduction of oral prednisone dose to less than 50% of average dose of preceding 3 months or less than 10 mg/day (whichever smaller)

Secondary Outcome Measures :

1. Participants With Normalization of Eosinophil Count at 6 Months [ Time Frame: 6 months after beginning of remission induction regimen ]
   Normalization of eosinophil counts was defined as total eosinophil counts <1.5 x 10^9/L.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with Churg-Strauss syndrome as defined by meeting one of 3 sets of criteria for Churg-Strauss Syndrome described above who have not yet been treated, who have failed steroid therapy (partial or non-responders) or who can not been tapered off oral prednisone because of documented relapsing disease
• Renal involvement (>25% dysmorphic red cell, red blood cell casts, or pauci-immune glomerulonephritis on biopsy)
• Age >18 years old
• Serum creatinine less than or equal to 3.0 mg/dl
• Able and willing to give written informed consent and comply with the requirements of the study protocol.
• Negative serum pregnancy test (for women of child bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment.

Exclusion Criteria

• Severe obstructive or restrictive lung disease (forced expiratory volume in one second <1)
• Cerebral involvement
• Rapidly progressive optic neuropathy or retinal vasculitis
• Active gastrointestinal bleeding
• Heart failure, including pericarditis or myocarditis.
• Hemoglobin <8.5 gm/dL
• Platelets <100,000/mm
• AST or ALT >2.5 Upper Limit of Normal unless related to primary disease
• Positive Hepatitis B or C serology
• History of positive HIV testing
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
• Previous treatment with Rituximab
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of recurrent significant infection or history of recurrent bacterial infections
• Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• Lack of peripheral venous access
• History of drug, alcohol, or chemical abuse within 6 months prior to screening
• Pregnancy or lactation
• Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Fernando Fervenza

Genentech, Inc.

Biogen

National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Fernando C. Fervenza, M.D., Ph.D.; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

Publications of Results:

Cartin-Ceba R, Keogh KA, Specks U, Sethi S, Fervenza FC. Rituximab for the treatment of Churg-Strauss syndrome with renal involvement. Nephrol Dial Transplant. 2011 Sep;26(9):2865-71. doi: 10.1093/ndt/gfq852. Epub 2011 Feb 16.

• Responsible Party: Fernando Fervenza, MD, PhD, Professor of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00424749
• Other Study ID Numbers: 06-004767; UL1RR024150 ( U.S. NIH Grant/Contract )
• First Posted: January 22, 2007
• Results First Posted: December 8, 2011
• Last Update Posted: December 8, 2011
• Last Verified: November 2011

Keywords provided by Fernando Fervenza, Mayo Clinic:

Antineutrophil cytoplasmic antibody associated vasculitis; Glomerulonephritis; Rituximab

Additional relevant MeSH terms:

Churg-Strauss Syndrome; Syndrome; Disease; Pathologic Processes; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases; Prednisone; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal