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

NCT02169219 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2012P001427
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Granulomatosis With Polyangiitis; Microscopic Polyangiitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Disease Response

  4 weeks

• Partial Remission

  8 weeks

• Sustained Complete Remission

  6 months

• Limited Flares

  6 months

• Severe Flares

  6 months

Study Arms (1)

Glucocorticoids and Rituximab

EXPERIMENTAL

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; Drug: Rituximab

Interventions

Glucocorticoids DRUG

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

Also known as: Prednisone

Glucocorticoids and Rituximab

Rituximab DRUG

Rituximab will be administered in four weekly doses at 375mg/m2

Also known as: Rituxan

Glucocorticoids and Rituximab

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Microscopic Polyangiitis

Interventions

Glucocorticoids; Prednisone; Rituximab

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. John Stone
• Organization: Massachusetts General Hospital, Division of Rheumatology

adfernandes@mgh.harvard.edu

617-643-2140

Study Officials

• John H Stone, MD

  Massachusetts General Hospital and Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 19, 2014
• First Posted: June 23, 2014
• Study Start: June 1, 2014
• Primary Completion: August 17, 2016
• Study Completion: November 1, 2017
• Last Updated: June 25, 2021
• Results First Posted: August 17, 2018

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)