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A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN) (BEGIN)

Primary Purpose

Systemic Lupus Erythematosus

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Prednisone
Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)
Methylprednisolone
Ocrelizumab
Placebo
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring SLE

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 16 years or above at the time of screening
  • Diagnosis of SLE
  • Active disease at screening

Exclusion Criteria:

  • Presence of active moderate to severe glomerulonephritis
  • Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia
  • Lack of peripheral venous access
  • Pregnancy or breast feeding mothers
  • History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin
  • Known severe chronic pulmonary disease
  • Evidence of significant or uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would impair patient participation
  • Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled) at any time in the 52 weeks prior to screening
  • Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection
  • Known active infection of any kind (but excluding fungal infection of nail beds or oral thrush which has resolved before Day 1) within 30 days prior to Day 1. In addition, any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives in the 30 days prior to Day 1 or oral anti-infectives in the 14 days prior to Day 1
  • History of serious recurrent or chronic infection
  • History of cancer (except basal cell carcinoma of the skin that has been excised and cured)
  • History of alcohol or drug abuse in the 52 weeks prior to screening
  • Major surgery in the 4 weeks prior to screening excluding diagnostic surgery
  • Previous treatment with CAMPATH-1H
  • Previous treatment with a BAFF directed treatment in the 12 months prior to screening
  • Previous treatment with a B-cell targeted therapy other than one directed at BAFF
  • Treatment with any investigational agent, other than those above, in the 28 days prior to screening or five half-lives of the investigational drug (whichever is longer)
  • Receipt of any live vaccine in the 6 weeks prior to Day 1
  • Intolerance or contraindication to oral or i.v. corticosteroids
  • Treatment with a second immunosuppressive or immunomodulatory drug in the 8 weeks prior to Day 1
  • Prednisone dose of ≥ 0.7 mg/kg/day (or equivalent) for > 7 of the previous 30 days prior to screening
  • Treatment with cyclophosphamide or a calcineurin inhibitor in the 12 weeks prior to screening
  • Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Ocrelizumab 1000 mg

    Ocrelizumab 400 mg

    Placebo

    Arm Description

    Ocrelizumab was administered i.v. at a dose on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks

    Ocrelizumab was administered at a dose 400 mg i.v. on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks

    Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks

    Outcomes

    Primary Outcome Measures

    Number of Participants With Major Clinical Response (MCR)
    Number of Participants With Partial Clinical Response (PCR)
    Number of Non-responders (NR)

    Secondary Outcome Measures

    Number of Participants Who Achieved a BILAG Score of C or Better at Week 24.
    Time Adjusted Mean SLEDAI-2K Score
    Annualized Flare Rate
    Time to First Moderate to Severe Flare
    Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96
    Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72
    Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96
    Change in SF-36 Subscale And Summary Scores From Baseline At Week 48
    Change In FACIT-Fatigue Assessment From Baseline To Week 48
    Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48
    The EQ-5D Single Index Utility Score At Week 48
    Number of Participants With Adverse Events

    Full Information

    First Posted
    October 3, 2007
    Last Updated
    August 27, 2020
    Sponsor
    Genentech, Inc.
    Collaborators
    Roche Pharma AG
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00539838
    Brief Title
    A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN)
    Acronym
    BEGIN
    Official Title
    A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Terminated
    Why Stopped
    The study was terminated prematurely when the decision was made that ocrelizumab was not likely to benefit this patient population.
    Study Start Date
    December 19, 2007 (Actual)
    Primary Completion Date
    July 12, 2011 (Actual)
    Study Completion Date
    July 12, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Genentech, Inc.
    Collaborators
    Roche Pharma AG

    4. Oversight

    5. Study Description

    Brief Summary
    This is a Phase III, randomized, double blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of ocrelizumab compared to placebo when combined with a single stable background immunosuppressive medication and a corticosteroid regimen in patients with moderately to severely active systemic lupus erythematosus, who do not have moderate to severe glomerulonephritis.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Systemic Lupus Erythematosus
    Keywords
    SLE

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    33 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ocrelizumab 1000 mg
    Arm Type
    Experimental
    Arm Description
    Ocrelizumab was administered i.v. at a dose on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks
    Arm Title
    Ocrelizumab 400 mg
    Arm Type
    Experimental
    Arm Description
    Ocrelizumab was administered at a dose 400 mg i.v. on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Prednisone
    Intervention Description
    Oral repeating dose
    Intervention Type
    Drug
    Intervention Name(s)
    Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)
    Intervention Description
    Oral repeating dose
    Intervention Type
    Drug
    Intervention Name(s)
    Methylprednisolone
    Intervention Description
    Intravenous repeating dose
    Intervention Type
    Drug
    Intervention Name(s)
    Ocrelizumab
    Intervention Description
    Intravenous repeating dose
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Intravenous repeating dose
    Primary Outcome Measure Information:
    Title
    Number of Participants With Major Clinical Response (MCR)
    Time Frame
    Week 48
    Title
    Number of Participants With Partial Clinical Response (PCR)
    Time Frame
    Week 48
    Title
    Number of Non-responders (NR)
    Time Frame
    Week 48
    Secondary Outcome Measure Information:
    Title
    Number of Participants Who Achieved a BILAG Score of C or Better at Week 24.
    Time Frame
    Week 24
    Title
    Time Adjusted Mean SLEDAI-2K Score
    Time Frame
    Week 48
    Title
    Annualized Flare Rate
    Time Frame
    Week 48 to Week 96
    Title
    Time to First Moderate to Severe Flare
    Time Frame
    Week 48 to Week 96
    Title
    Number of Participants Who Achieved A Major Or Partial Clinical Response At Week 48 (PCR Plus MCR Proportion), Who Did Not Experience A Flare Before Week 96
    Time Frame
    Week 48 to Week 96
    Title
    Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72
    Time Frame
    Week 48 to Week 72
    Title
    Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96
    Time Frame
    Week 48 to Week 96
    Title
    Change in SF-36 Subscale And Summary Scores From Baseline At Week 48
    Time Frame
    Baseline, Week 48
    Title
    Change In FACIT-Fatigue Assessment From Baseline To Week 48
    Time Frame
    Baseline, Week 48
    Title
    Change From Baseline In Pain Quality And Impact Of Pain On Daily Function Measured By The Brief Pain Inventory Short Form At Week 48
    Time Frame
    Baseline, Week 48
    Title
    The EQ-5D Single Index Utility Score At Week 48
    Time Frame
    Baseline, Week 48
    Title
    Number of Participants With Adverse Events
    Time Frame
    Up to 2.5 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age 16 years or above at the time of screening Diagnosis of SLE Active disease at screening Exclusion Criteria: Presence of active moderate to severe glomerulonephritis Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia Lack of peripheral venous access Pregnancy or breast feeding mothers History of severe allergic or anaphylactic reactions to humanized, chimeric or murine monoclonal antibodies or i.v. immunoglobulin Known severe chronic pulmonary disease Evidence of significant or uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would impair patient participation Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled) at any time in the 52 weeks prior to screening Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection Known active infection of any kind (but excluding fungal infection of nail beds or oral thrush which has resolved before Day 1) within 30 days prior to Day 1. In addition, any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives in the 30 days prior to Day 1 or oral anti-infectives in the 14 days prior to Day 1 History of serious recurrent or chronic infection History of cancer (except basal cell carcinoma of the skin that has been excised and cured) History of alcohol or drug abuse in the 52 weeks prior to screening Major surgery in the 4 weeks prior to screening excluding diagnostic surgery Previous treatment with CAMPATH-1H Previous treatment with a BAFF directed treatment in the 12 months prior to screening Previous treatment with a B-cell targeted therapy other than one directed at BAFF Treatment with any investigational agent, other than those above, in the 28 days prior to screening or five half-lives of the investigational drug (whichever is longer) Receipt of any live vaccine in the 6 weeks prior to Day 1 Intolerance or contraindication to oral or i.v. corticosteroids Treatment with a second immunosuppressive or immunomodulatory drug in the 8 weeks prior to Day 1 Prednisone dose of ≥ 0.7 mg/kg/day (or equivalent) for > 7 of the previous 30 days prior to screening Treatment with cyclophosphamide or a calcineurin inhibitor in the 12 weeks prior to screening Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jorn Drappa, M.D., Ph.D.
    Organizational Affiliation
    Genentech, Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
    Links:
    URL
    http://www.roche-trials.com/trialDetailsGet.action?studyNumber=WA20499&productGenericName=ocrelizumab&productType=Drug&divisionName=PHA
    Description
    Ex-U.S. Study Information (Ex-US this trial is sponsored/managed by Hoffmann-La Roche)

    Learn more about this trial

    A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN)

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