Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis (SCOUT)
Primary Purpose
Granulomatosis With Polyangiitis, Microscopic Polyangiitis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Glucocorticoids
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Granulomatosis With Polyangiitis
Eligibility Criteria
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
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Glucocorticoids and Rituximab
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Partial Remission
Number of patients entering partial remission, defined as no new disease manifestations, no worsening of existing disease and BVAS/WG < 3.
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.
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
Severe Flares
Number of severe flares defined as flare with BVAS/WG > 3 or experiencing one of the major BVAS/WG items
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
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.
Full Information
NCT ID
NCT02169219
First Posted
June 19, 2014
Last Updated
June 23, 2021
Sponsor
Massachusetts General Hospital
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02169219
Brief Title
Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis
Acronym
SCOUT
Official Title
Short-Course Glucocorticoids and Rituximab in ANCA-Associated Vasculitis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
August 17, 2016 (Actual)
Study Completion Date
November 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Granulomatosis With Polyangiitis, Microscopic Polyangiitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Glucocorticoids and Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Glucocorticoids
Other Intervention Name(s)
Prednisone
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Rituximab will be administered in four weekly doses at 375mg/m2
Primary Outcome Measure Information:
Title
Complete Remission
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Disease Response
Description
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.
Time Frame
4 weeks
Title
Partial Remission
Description
Number of patients entering partial remission, defined as no new disease manifestations, no worsening of existing disease and BVAS/WG < 3.
Time Frame
8 weeks
Title
Sustained Complete Remission
Description
Number of patients entering sustained remission defined as BVAS/WG = 0, prednisone dose = 0 and no disease flares during the study period.
Time Frame
6 months
Title
Limited Flares
Description
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
Time Frame
6 months
Title
Severe Flares
Description
Number of severe flares defined as flare with BVAS/WG > 3 or experiencing one of the major BVAS/WG items
Time Frame
6 months
Title
Early Treatment Failures
Description
Number of early treatment failures defined as patients who have new or worsening disease manifestations assessed at 4 weeks after study entry
Time Frame
4 weeks
Title
Vasculitis Damage Index (VDI)
Description
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.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John H Stone, MD
Organizational Affiliation
Massachusetts General Hospital and Harvard Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data will be shared upon request - without personal health information - following completion of the analysis. Inquiries should be directed to the Principal Investigator.
Learn more about this trial
Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis
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