A Study to Evaluate Two Doses of Ocrelizumab in Patients With Active Systemic Lupus Erythematosus (BEGIN)
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Prednisone; Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate); Methylprednisolone; Ocrelizumab; Placebo
Intervention description: Oral repeating dose; Oral repeating dose; Intravenous repeating dose; Intravenous repeating dose; Intravenous repeating dose
Intervention MeSH terms: Mycophenolic Acid; Prednisone; Methylprednisolone; Methotrexate; Azathioprine; Immunosuppressive Agents; Ocrelizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 33.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: SLE

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.
    

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