Churg-Strauss Syndrome
Conditions
Keywords
Antineutrophil cytoplasmic antibody associated vasculitis, Glomerulonephritis, Rituximab
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.
Interventions
DRUGRituximab
Patients received 4 weekly doses of rituximab 375 mg/m\^2.
DRUGPrednisone
Prednisone 1 mg/kg/day (not to exceed 80 mg/day) for 4 weeks followed by a taper to 0 mg by 6 months
Sponsors
Genentech, Inc.
Biogen
National Center for Research Resources (NCRR)
Fernando Fervenza
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Remission of Renal Disease Activity at 3 Months | 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
| Measure | Time frame | Description |
|---|---|---|
| Participants With Normalization of Eosinophil Count at 6 Months | 6 months after beginning of remission induction regimen | Normalization of eosinophil counts was defined as total eosinophil counts \<1.5 x 10\^9/L. |
Countries
United States
Participant flow
Recruitment details
This study was done between June 2007 and July 2009. Participants were enrolled at the Mayo Clinic in Rochester, MN.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab 375 mg/m\^2/week for 4 weeks | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Participants With Remission of Renal Disease Activity at 3 Months
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)
Time frame: 3 months after beginning of remission induction regimen
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Participants With Remission of Renal Disease Activity at 3 Months | 3 participants |
Secondary
Participants With Normalization of Eosinophil Count at 6 Months
Normalization of eosinophil counts was defined as total eosinophil counts \<1.5 x 10\^9/L.
Time frame: 6 months after beginning of remission induction regimen
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Participants With Normalization of Eosinophil Count at 6 Months | 2 participants |