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

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02169219
Collaborator
Genentech, Inc. (Industry)
20
1
1
41
0.5

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Short-Course Glucocorticoids and Rituximab in ANCA-Associated Vasculitis
Study Start Date :
Jun 1, 2014
Actual Primary Completion Date :
Aug 17, 2016
Actual Study Completion Date :
Nov 1, 2017

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Complete Remission [6 months]

      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

    1. Disease Response [4 weeks]

      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.

    2. Partial Remission [8 weeks]

      Number of patients entering partial remission, defined as no new disease manifestations, no worsening of existing disease and BVAS/WG < 3.

    3. Sustained Complete Remission [6 months]

      Number of patients entering sustained remission defined as BVAS/WG = 0, prednisone dose = 0 and no disease flares during the study period.

    4. Limited Flares [6 months]

      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

    5. Severe Flares [6 months]

      Number of severe flares defined as flare with BVAS/WG > 3 or experiencing one of the major BVAS/WG items

    6. Early Treatment Failures [4 weeks]

      Number of early treatment failures defined as patients who have new or worsening disease manifestations assessed at 4 weeks after study entry

    7. Vasculitis Damage Index (VDI) [24 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Boston Massachusetts United States 02114

    Sponsors and Collaborators

    • Massachusetts General Hospital
    • Genentech, Inc.

    Investigators

    • Principal Investigator: John H Stone, MD, Massachusetts General Hospital and Harvard Medical School

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Stone, John H, M.D., M.P.H, Professor of Medicine, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT02169219
    Other Study ID Numbers:
    • 2012P001427
    First Posted:
    Jun 23, 2014
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details New diagnosis or flare of previously diagnosed disease in patients followed in the Massachusetts General Hospital (MGH) Rheumatology or Nephrology Units. New diagnosis or flare of previously diagnosed disease in patients hospitalized at MGH.
    Pre-assignment Detail
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
    Period Title: Overall Study
    STARTED 20
    COMPLETED 14
    NOT COMPLETED 6

    Baseline Characteristics

    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group 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. 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
    Overall Participants 20
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    16
    80%
    >=65 years
    4
    20%
    Sex: Female, Male (Count of Participants)
    Female
    13
    65%
    Male
    7
    35%
    Region of Enrollment (Count of Participants)
    United States
    20
    100%
    Birmingham Vasculitis Activity Score for Wegener's Granulomatosis(BVAS/WG) (units on a scale) [Mean (Full Range) ]
    Mean (Full Range) [units on a scale]
    5
    Disease group (Count of Participants)
    Granulomatosis with polyangiitis (GPA)
    14
    70%
    Microscopic polyangiitis (MPA)
    6
    30%
    Indeterminate
    0
    0%
    anti-neutrophil cytoplasmic antibody (ANCA) (Count of Participants)
    myeloperoxidase (MPO)
    11
    55%
    proteinase (PR3)
    7
    35%
    Negative
    2
    10%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description 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 will be administered in four weekly doses at 375mg/m2
    Measure Participants 20
    Count of Participants [Participants]
    14
    70%
    2. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Number of patients having a disease response
    Arm/Group Title Rituximab and Glucocorticoids
    Arm/Group Description 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 administered in 4 weekly doses at 375 mg/m2
    Measure Participants 20
    Count of Participants [Participants]
    20
    100%
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
    Measure Participants 20
    Count of Participants [Participants]
    20
    100%
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
    Measure Participants 20
    Count of Participants [Participants]
    14
    70%
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description 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
    Measure Participants 20
    Count of Participants [Participants]
    2
    10%
    6. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group 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. 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
    Measure Participants 20
    Count of Participants [Participants]
    5
    25%
    7. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description All patients receive both rituximab and glucocorticoids. The protocol calls for the discontinuation of prednisone within two months of the baseline visit.
    Measure Participants 20
    Count of Participants [Participants]
    0
    0%
    8. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group Description Measure Description: Disease damage was assessed by the Vasculitis Damage Index (VDI) at baseline and end of study
    Measure Participants 20
    Baseline VDI score
    0
    24 month VDI score
    0.5

    Adverse Events

    Time Frame Reports of unanticipated problems involving risks to subjects or others are to be submitted to the IRB within 5 working days/7 calendar days of the date the investigator first becomes aware of the problem. Adverse events were collected through the 6 month study duration.
    Adverse Event Reporting Description Serious adverse event means any event temporally associated with the subject's participation in research that meets any of the following criteria: 1) hospitalization or prolonged hospitalization 2.)One severe flare - defined as BVAS/WG ≥ 3 or experiencing one of the major BVAS/WG items) 3.) unexpected and related to the investigation drug
    Arm/Group Title Glucocorticoids and Rituximab
    Arm/Group 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 Rituximab: Rituximab will be administered in four weekly doses at 375mg/m2
    All Cause Mortality
    Glucocorticoids and Rituximab
    Affected / at Risk (%) # Events
    Total 0/20 (0%)
    Serious Adverse Events
    Glucocorticoids and Rituximab
    Affected / at Risk (%) # Events
    Total 11/20 (55%)
    Cardiac disorders
    myocardial infarction 1/20 (5%) 1
    atrial fibrillation, 1/20 (5%) 1
    Endocrine disorders
    Thyroid maligancy 2/20 (10%) 2
    Immune system disorders
    Severe flares 5/20 (25%) 5
    syncope 1/20 (5%) 1
    Reproductive system and breast disorders
    Uterine malignancy 1/20 (5%) 1
    Other (Not Including Serious) Adverse Events
    Glucocorticoids and Rituximab
    Affected / at Risk (%) # Events
    Total 0/20 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. John Stone
    Organization Massachusetts General Hospital, Division of Rheumatology
    Phone 617-643-2140
    Email adfernandes@mgh.harvard.edu
    Responsible Party:
    Stone, John H, M.D., M.P.H, Professor of Medicine, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT02169219
    Other Study ID Numbers:
    • 2012P001427
    First Posted:
    Jun 23, 2014
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    Jun 1, 2021