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

Short-Course Glucocorticoids and Rituximab in ANCA-Associated Vasculitis

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.

Study Overview

• Status: Completed
• Conditions: Microscopic Polyangiitis; Granulomatosis With Polyangiitis
• Intervention / Treatment: Drug: Glucocorticoids; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Glucocorticoids and Rituximab; 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; 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; Other Names: Prednisone; Drug: Rituximab; Rituximab will be administered in four weekly doses at 375mg/m2; Other Names: Rituxan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 17, 2016
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: June 19, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Lung Diseases; Lung Diseases, Interstitial; Cerebral Small Vessel Diseases; Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Rituximab; Prednisone; Glucocorticoids
• Other Study ID Numbers: 2012P001427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• 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