Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis

Study Overview
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Brief Summary
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The purpose of this pilot study is to test whether an 8-week course of glucocorticoids, combined with rituximab, is effective in treating ANCA-associated vasculitis.

Detailed Description
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The primary aim of this pilot study is to examine whether an 8 week course of glucocorticoids, in combination with rituximab, is effective in inducing and maintaining disease remission for up to 6 months in a subset of patients with ANCA-associated vasculitis (AAV) who have a more favorable prognosis. This pilot study will enroll 20 patients with active AAV. Close patient follow-up will insure that any patients who require courses of glucocorticoids longer than two months will receive longer therapy, if appropriate for their well-being.

Official Title
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Short-Course Glucocorticoids and Rituximab in ANCA-Associated Vasculitis

Conditions
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Granulomatosis With Polyangiitis, Microscopic Polyangiitis

Intervention / Treatment
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* Drug: Glucocorticoids
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ages 18-85 years old Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference New diagnosis or disease flare with a Birmingham Vasculitis Activity Score/Wegener's granulomatosis (BVAS/WG) of > 3 Exclusion Criteria: Renal disease in patients with PR3-ANCA as defined by any of the following: Urinary red blood cell casts Biopsy-proven glomerulonephritis Increase in serum creatinine of >30% over baseline Severe renal disease in patients with MPO-ANCA as defined by both of the following: Urinary red blood cell casts or biopsy-proven glomerulonephritis Estimated glomerular filtration rate < 30 ml/min/1.73m2 Diffuse alveolar hemorrhage requiring ventilatory support GC treatment for longer than 14 days prior to enrollment unless patient has been on a stable maintenance dose of prednisone at the time of the flare Daily oral cyclophosphamide within 1 month prior to enrollment Completed a remission induction course of cyclophosphamide or rituximab within 4 months of enrollment Hepatitis B infection HIV infection History of anti-GBM disease Other uncontrolled disease, including drug and alcohol abuse, that may interfere with the study Pregnancy or breastfeeding History of severe allergic reactions to human or chimeric monoclonal antibodies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glucocorticoids and Rituximab<br>This is a single-arm trial. All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit. | Drug: Glucocorticoids<br>* Patients will begin prednisone therapy at a dose selected by the investigator or the treating physician with oral prednisone 60mg or 1mg/kg (if weight less than 60kg) or intravenous methylprednisolone, up to 1g/day for three days. Prednisone will be tapered over 8 weeks as follows: 60mg for 2 weeks 40mg for 2 weeks 30mg for 1 week 20mg for 1 week 10mg for 1 week 5mg for 1 week<br>* Other names: Prednisone;Drug: Rituximab<br>* Rituximab will be administered in four weekly doses at 375mg/m2<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission | We examined whether an 8-week glucocorticoid course in combination with rituximab (RTX) would induce disease remission in patients with AAV. The primary outcome was disease remission off steroids at 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Response | Number of patients achieving disease response defined as, no new disease manifestations; no worsening of existing disease; stable or improved BVAS/WG score at 4 weeks. | 4 weeks | 
| Partial Remission | Number of patients entering partial remission, defined as no new disease manifestations, no worsening of existing disease and BVAS/WG < 3. | 8 weeks | 
| Sustained Complete Remission | Number of patients entering sustained remission defined as BVAS/WG = 0, prednisone dose = 0 and no disease flares during the study period. | 6 months | 
| Limited Flares | Number of limited flares defined as a new occurrence or worsening of one or more minor BVAS/WG items and a total BVAS/WG ≤ 3 | 6 months | 
| Severe Flares | Number of severe flares defined as flare with BVAS/WG > 3 or experiencing one of the major BVAS/WG items | 6 months | 
| Early Treatment Failures | Number of early treatment failures defined as patients who have new or worsening disease manifestations assessed at 4 weeks after study entry | 4 weeks | 
| Vasculitis Damage Index (VDI) | The Vasculitis Damage Index (VDI) is a single-page catalog of damage items separated into 11 groupings of items by organ system. There are a total of 60 items. Each item is recorded if it occurred since the onset of vasculitis, has been present for at least 3 months, or occurred at least 3 months ago. Each item of damage is scored as present (1) or absent (0), yielding a maximum score of 60. | 24 months |