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

Microscopic Polyangiitis Clinical Trial

— SCOUT  

Official title:

Short-Course Glucocorticoids and Rituximab in ANCA-Associated Vasculitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02169219
• Other study ID #: 2012P001427
• Status: Completed
• Phase: Phase 4
• Start date: June 2014
• Est. completion date: November 1, 2017

Study information

• Verified date: June 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 1, 2017
• Est. primary completion date: August 17, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Granulomatosis With Polyangiitis
• Microscopic Polyangiitis
• Systemic Vasculitis
• Vasculitis

Intervention

Drug:
• Glucocorticoids
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
• Rituximab
Rituximab will be administered in four weekly doses at 375mg/m2

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Severe Flares	Number of severe flares defined as flare with BVAS/WG > 3 or experiencing one of the major BVAS/WG items	6 months
Secondary	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
Secondary	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