Clinical trial NCT00424749: Rituxan in Churg Strauss Syndrome With Renal Involvement
Official title: A Pilot Study on the Use of Rituximab in the Treatment of Churg- Strauss Syndrome With Renal Involvement
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Churg-Strauss Syndrome
Keywords: Antineutrophil cytoplasmic antibody associated vasculitis
Glomerulonephritis
Rituximab
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Biogen
name: National Center for Research Resources (NCRR)
First posted: 2007-01-22
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Participants With Remission of Renal Disease Activity at 3 Months
timeFrame: 3 months after beginning of remission induction regimen
Secondary outcomes:
measure: Participants With Normalization of Eosinophil Count at 6 Months
timeFrame: 6 months after beginning of remission induction regimen
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Fernando C. Fervenza, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.