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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Prednisone
* Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)
* Drug: Methylprednisolone
* Drug: Ocrelizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ocrelizumab 1000 mg<br>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 | Drug: Prednisone<br>* Oral repeating dose<br>Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)<br>* Oral repeating dose<br>Drug: Methylprednisolone<br>* Intravenous repeating dose<br>Drug: Ocrelizumab<br>* Intravenous repeating dose<br>|
| Experimental: Ocrelizumab 400 mg<br>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 | Drug: Prednisone<br>* Oral repeating dose<br>Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)<br>* Oral repeating dose<br>Drug: Methylprednisolone<br>* Intravenous repeating dose<br>Drug: Ocrelizumab<br>* Intravenous repeating dose<br>|
| Placebo Comparator: Placebo<br>Placebo infusions were administered on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks | Drug: Immunosuppressive regime (azathioprine, mycophenolate mofetil or methotrexate)<br>* Oral repeating dose<br>Drug: Placebo<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major Clinical Response (MCR) |  | Week 48 | 
| Number of Participants With Partial Clinical Response (PCR) |  | Week 48 | 
| Number of Non-responders (NR) |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved a BILAG Score of C or Better at Week 24. |  | Week 24 | 
| Time Adjusted Mean SLEDAI-2K Score |  | Week 48 | 
| Annualized Flare Rate |  | Week 48 to Week 96 | 
| Time to First Moderate to Severe Flare |  | Week 48 to Week 96 | 
| 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 |  | Week 48 to Week 96 | 
| Number of Participants Who Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 72 |  | Week 48 to Week 72 | 
| Number of Participants Achieved A MCR At Week 48, Who Did Not Experience A Flare Before Week 96 |  | Week 48 to Week 96 | 
| Change in SF-36 Subscale And Summary Scores From Baseline At Week 48 |  | Baseline, Week 48 | 
| Change In FACIT-Fatigue Assessment From Baseline To Week 48 |  | Baseline, 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 |  | Baseline, Week 48 | 
| The EQ-5D Single Index Utility Score At Week 48 |  | Baseline, Week 48 | 
| Number of Participants With Adverse Events |  | Up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE