A Study to Evaluate Ocrelizumab in Patients With Nephritis Due to Systemic Lupus Erythematosus (BELONG)

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00626197
• Collaborator: Roche Pharma AG (Industry)
• Enrollment: 381
• Arms: 3
• Actual Duration (Months): 68.4

Study Details

Study Description

Brief Summary

This is a Phase III, randomized, double-blind, placebo-controlled, multicentre, parallel-group study designed to evaluate the efficacy and safety of ocrelizumab added to SOC (corticosteroid plus one of two immunosuppressant regimens) compared with placebo added to SOC in patients with WHO or ISN Class III or IV lupus nephritis.

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis; Systemic Lupus Erythematosus	Drug: Corticosteroids; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Ocrelizumab; Drug: Placebo; Drug: Azathioprine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 381 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 WHO or ISN Class III or IV Nephritis Due to Systemic Lupus Erythematosus
• Actual Study Start Date: Feb 15, 2008
• Actual Primary Completion Date: Oct 19, 2009
• Actual Study Completion Date: Oct 28, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OCR 400 mg + SOC Participants received Ocrelizumab 400 mg i.v. infusion on Days 1 and 15, followed by 400 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.	Drug: Corticosteroids; Intravenous and oral repeating dose; Drug: Cyclophosphamide; Cyclophosphamide was administered at a IV dose 500 mg every 2 weeks for up to 6 doses followed by maintenance treatment with azathioprine.; Drug: Mycophenolate Mofetil; Mycophenolate Mofetil was administered orally at maximum dose of 3 g/day.; Drug: Ocrelizumab; Ocrelizumab was administed at a dose and as per schedule in arm description; Drug: Azathioprine; Azathioprine was administered at a dose up to 2 mg/kg/day with a maximum dose of 200 mg.
Experimental: OCR 1000 mg + SOC Participants received Ocrelizumab 1000 mg i.v. infusion on Days 1 and 15, followed by 1000 mg i.v. at Week 16 and then every 16 weeks plus SOC regimen.	Drug: Corticosteroids; Intravenous and oral repeating dose; Drug: Cyclophosphamide; Cyclophosphamide was administered at a IV dose 500 mg every 2 weeks for up to 6 doses followed by maintenance treatment with azathioprine.; Drug: Mycophenolate Mofetil; Mycophenolate Mofetil was administered orally at maximum dose of 3 g/day.; Drug: Ocrelizumab; Ocrelizumab was administed at a dose and as per schedule in arm description; Drug: Azathioprine; Azathioprine was administered at a dose up to 2 mg/kg/day with a maximum dose of 200 mg.
Placebo Comparator: Placebo + SOC Participants received placebo i.v. infusion on Days 1 and 15, followed by placebo infusion at Week 16 and then every 16 weeks plus SOC regimen.	Drug: Corticosteroids; Intravenous and oral repeating dose; Drug: Cyclophosphamide; Cyclophosphamide was administered at a IV dose 500 mg every 2 weeks for up to 6 doses followed by maintenance treatment with azathioprine.; Drug: Mycophenolate Mofetil; Mycophenolate Mofetil was administered orally at maximum dose of 3 g/day.; Drug: Placebo; Placebo was administered as per schedule in arm description; Drug: Azathioprine; Azathioprine was administered at a dose up to 2 mg/kg/day with a maximum dose of 200 mg.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved Complete Renal Response (CRR) [Week 48]

   CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent [%] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (>) 3, a urine protein:urine creatinine ratio of less than (<) 3 needed to be achieved.

2. Percentage of Participants Who Achieved Overall Response [Week 48]

   Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is >3, a urine protein:urine creatinine ratio of <3 needs to be achieved.

Secondary Outcome Measures

1. Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48 [Weeks 36, 40, 44, and 48]

2. Time To Complete Renal Response [Baseline up to Week 48]

   Time to complete renal response was proposed to be analyzed using a stratified log rank test with race and SOC as stratification factors. Comparisons of ocrelizumab versus placebo were to be expressed as p-values, estimated hazard ratios, adjusted proportions of participants who achieved a complete renal response and their 95% confidence intervals. Kaplan-Meier curves were to be produced. Due to early termination of the study the analyses were not performed.

3. Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48 [Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48]

   The improvement of AUC of cGFR was to be measured between Baseline and Week 48. This was to be analyzed with Analysis of Covariance (ANCOVA) with race and SOC as covariates.

4. Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score [Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48]

   SLEDAI-2K measures disease activity at the visit or within the preceding 10 days. It comprised of 24 descriptors, covering 9 organ systems, and reflects disease activity over the previous 10 days.The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity

5. Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response [Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48]

   Renal flares may be either proteinuric or nephritic as defined below: Proteinuric Flares are defined as follows:In participants who achieve a urine protein:urine creatinine (Upr:Ucr) ≤ 0.5, an increase to Upr:Ucr >1; In participants with an Upr:Ucr >0.5, a doubling of Upr:Ucr (with a minimum increase to Upr:Ucr >2). Nephritic Flare defined as: Increase in serum creatinine of ≥30% from the lowest value achieved in the study accompanied by Increase Upr:Ucr >1 Or New/worsening active urine sediment on two consecutive occasions, in the absence of urinary tract infection or other causes of hematuria.

6. Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) From Baseline to Week 48 [Baseline and Weeks 1, 12, 24, 36, and 48]

   The SF36 Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions physical role functioning, emotional role functioning, social role functioning, and mental health.

7. Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire From Baseline to Week 48 [Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48]

   The FACIT Fatigue Scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued).

8. Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) From Baseline to Week 48 [Baseline and Weeks 1, 12, 24, 36, and 48]

   m-BPI-sf is a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. A single item pertains to worst pain in the past 24 hours with a range of 0 (no pain) to 10 (worst imaginable pain).

9. Health Care Visits Over the 48-Week Treatment Period [Weeks 1, 24, and 48]

   The number of health care visits (including doctor's office visits, Emergency room/ Accident and Emergency [ER/A&E] visits and hospitalizations) over the 48-week treatment period were recorded.

10. Percentage of Participants Who Achieved a CRR or PRR And Who Received A Corticosteroid Dose of <10 Milligrams Per Day (mg/Day) From Week 24 to Week 48 [Week 48]

    CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein:urine creatinine ratio of <3 needed to be achieved.

11. Percentage of Participants Who Achieved a CRR or PRR And Who Received a Corticosteroid Dose of <5 mg/Day by Week 48 [Week 48]

    CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein: urine creatinine ratio of <3 needed to be achieved.

12. Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks [Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48]

    AUC is the area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. AUC was to be used to determine the average corticosteroid burden.

13. Percentage of Participants Who Stopped Immunosuppressants After Week 48 [Week 48]

    The number of participants who stopped immunosuppressants were to be determined by survey.

14. Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit [Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32]

    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. CD19+ cells were measured as cells per microliter (cells/uL).

15. Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) [Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32]

    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. 0 represents 0% of participants.

16. Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit [Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32]

    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. n = number of participants analyzed at the specified visit. 0 represents 0% of participants.

17. Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit [Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32]

    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. <LLN = 80 cells/uL.

18. Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response [Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48]

    A major clinical response was defined as British Isles Lupus Assessment Group (BILAG) C scores or better at Week 24 without developing any new A or two new B scores up to Week 24 and maintenance of this response without developing a moderate or severe flare between Week 24 and Week 48. A partial clinical response was defined as BILAG C scores or better at Week 24 and maintaining this response without developing a flare for 16 consecutive weeks. The BILAG is an organ-specific 86-question assessment based on the principle of the doctor's intent to treat, which requires an assessment of improved (1), the same (2), worse (3), or new (4) over the last month. Within each organ system, multiple manifestations and laboratory tests are combined into a single score for that organ. The resulting scores for each organ can be A through E, where A is very active disease, B is moderate activity, C is mild stable disease, D is resolved activity, and E indicates the organ was never involved.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 16 years or above at the time of the screening

• Ability and willingness to provide written informed consent and to comply with the schedule of protocol requirements

• Diagnosis of SLE

• Active lupus nephritis

Exclusion Criteria:

• Currently active retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia

• Severe renal impairment

• 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 uncontrolled concomitant diseases in any organ system not related to SLE, which, in the investigator's opinion, would preclude patient participation

• Concomitant condition which has required treatment with systemic corticosteroid (excluding topical or inhaled steroids) prior to screening

• Known HIV or chronic active Hepatitis B or chronic active Hepatitis C infection

• Known active infection of any kind prior to Day 1

• History of serious recurrent or chronic infection

• History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except basal cell carcinoma of the skin that has been excised and cured).

• History of alcohol or drug abuse prior to screening

• Major surgery prior to screening, excluding diagnostic surgery

• Previous treatment with CAMPATH-1H

• Previous treatment with a BAFF directed treatment (e.g. anti-BLyS) prior to screening

• Previous treatment with a B-cell targeted therapy other than one directed at BAFF (e.g. anti-CD20, anti-CD22)

• Treatment with any investigational agent prior to screening

• Receipt of any live vaccines prior to Day 1

• Intolerance or contraindication to oral or i.v. corticosteroids

• Positive hepatitis BsAg or hepatitis C serology. Patients who are HBsAg negative but HBcAb positive may be enrolled with a negative DNA test

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Genentech, Inc.
• Roche Pharma AG

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT00626197
• Other Study ID Numbers: ACT4072g; WA20500
• First Posted: Feb 29, 2008
• Last Update Posted: Dec 22, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Genentech, Inc.: SLE; Lupus; BELONG
• Additional relevant MeSH terms: Nephritis; Lupus Nephritis; Lupus Erythematosus, Systemic; Mycophenolic Acid; Cyclophosphamide; Azathioprine; Ocrelizumab

Study Results

Participant Flow

Recruitment Details	Screening was done from Day -14 to Day -1.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Period Title: Overall Study
STARTED	127	128	126
COMPLETED	83	74	49
NOT COMPLETED	44	54	77

Baseline Characteristics

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC	Total
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Total of all reporting groups
Overall Participants	127	128	126	381
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.9 (10.2)	30.6 (8.9)	31.3 (9.9)	31.3 (9.7)
Sex: Female, Male (Count of Participants)
Female	115 90.6%	110 85.9%	107 84.9%	332 87.1%
Male	12 9.4%	18 14.1%	19 15.1%	49 12.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	17 13.4%	15 11.7%	17 13.5%	49 12.9%
Asian	39 30.7%	27 21.1%	35 27.8%	101 26.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	7 5.5%	7 5.5%	5 4%	19 5%
White	55 43.3%	67 52.3%	58 46%	180 47.2%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	9 7.1%	12 9.4%	11 8.7%	32 8.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved Complete Renal Response (CRR)
Description	CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent [%] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (>) 3, a urine protein:urine creatinine ratio of less than (<) 3 needed to be achieved.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The primary endpoint was analyzed via an overall response (CRR+PRR) analysis and the separate complete and partial response rates were only summarized descriptively

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	75	73	75
CRR	42.7 33.6%	31.5 24.6%	34.7 27.5%
PRR	24 18.9%	35.6 27.8%	20 15.9%

2. Primary Outcome

Title	Percentage of Participants Who Achieved Overall Response
Description	Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is >3, a urine protein:urine creatinine ratio of <3 needs to be achieved.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The primary endpoint was analyzed via an overall response (CRR+PRR) analysis and the separate complete and partial response rates were only summarized descriptively

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	75	73	75
Number (95% Confidence Interval) [Percentage of Participants]	66.7 52.5%	67.1 52.4%	54.7 43.4%

3. Secondary Outcome

Title	Percentage of Participants Who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48
Time Frame	Weeks 36, 40, 44, and 48

Outcome Measure Data

Analysis Population Description

Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

4. Secondary Outcome

Title	Time To Complete Renal Response
Description	Time to complete renal response was proposed to be analyzed using a stratified log rank test with race and SOC as stratification factors. Comparisons of ocrelizumab versus placebo were to be expressed as p-values, estimated hazard ratios, adjusted proportions of participants who achieved a complete renal response and their 95% confidence intervals. Kaplan-Meier curves were to be produced. Due to early termination of the study the analyses were not performed.
Time Frame	Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

5. Secondary Outcome

Title	Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48
Description	The improvement of AUC of cGFR was to be measured between Baseline and Week 48. This was to be analyzed with Analysis of Covariance (ANCOVA) with race and SOC as covariates.
Time Frame	Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

6. Secondary Outcome

Title	Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score
Description	SLEDAI-2K measures disease activity at the visit or within the preceding 10 days. It comprised of 24 descriptors, covering 9 organ systems, and reflects disease activity over the previous 10 days.The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity
Time Frame	Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

7. Secondary Outcome

Title	Time to First Renal Flare In Those Participants Who Demonstrated at Least a Partial Renal Response
Description	Renal flares may be either proteinuric or nephritic as defined below: Proteinuric Flares are defined as follows:In participants who achieve a urine protein:urine creatinine (Upr:Ucr) ≤ 0.5, an increase to Upr:Ucr >1; In participants with an Upr:Ucr >0.5, a doubling of Upr:Ucr (with a minimum increase to Upr:Ucr >2). Nephritic Flare defined as: Increase in serum creatinine of ≥30% from the lowest value achieved in the study accompanied by Increase Upr:Ucr >1 Or New/worsening active urine sediment on two consecutive occasions, in the absence of urinary tract infection or other causes of hematuria.
Time Frame	Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Outcome Measure Data

Analysis Population Description

Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

8. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) From Baseline to Week 48
Description	The SF36 Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions physical role functioning, emotional role functioning, social role functioning, and mental health.
Time Frame	Baseline and Weeks 1, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

9. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire From Baseline to Week 48
Description	The FACIT Fatigue Scale is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued).
Time Frame	Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

10. Secondary Outcome

Title	Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) From Baseline to Week 48
Description	m-BPI-sf is a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. A single item pertains to worst pain in the past 24 hours with a range of 0 (no pain) to 10 (worst imaginable pain).
Time Frame	Baseline and Weeks 1, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

11. Secondary Outcome

Title	Health Care Visits Over the 48-Week Treatment Period
Description	The number of health care visits (including doctor's office visits, Emergency room/ Accident and Emergency [ER/A&E] visits and hospitalizations) over the 48-week treatment period were recorded.
Time Frame	Weeks 1, 24, and 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

12. Secondary Outcome

Title	Percentage of Participants Who Achieved a CRR or PRR And Who Received A Corticosteroid Dose of <10 Milligrams Per Day (mg/Day) From Week 24 to Week 48
Description	CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein:urine creatinine ratio of <3 needed to be achieved.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

13. Secondary Outcome

Title	Percentage of Participants Who Achieved a CRR or PRR And Who Received a Corticosteroid Dose of <5 mg/Day by Week 48
Description	CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein: urine creatinine ratio of <3 needed to be achieved.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

14. Secondary Outcome

Title	Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks
Description	AUC is the area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. AUC was to be used to determine the average corticosteroid burden.
Time Frame	Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

15. Secondary Outcome

Title	Percentage of Participants Who Stopped Immunosuppressants After Week 48
Description	The number of participants who stopped immunosuppressants were to be determined by survey.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Due to the early termination and unblinding of the study, no data was collected for this endpoint and analysis was not performed.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

16. Secondary Outcome

Title	Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit
Description	CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. CD19+ cells were measured as cells per microliter (cells/uL).
Time Frame	Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Outcome Measure Data

Analysis Population Description

N = number of participants analyzed at the specified visit

Arm/Group Title	Placebo + SOC	OCR 400 mg + SOC	OCR 1000 mg + SOC	OCR + SOC	Placebo-Mycophenolate Mofetil (MMF)	Placebo-Euro Lupus (EL)
Arm/Group Description	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Measure Participants	75	73	70	141	45	27
Baseline	203.5 (191.4)	256.3 (300.2)	224.1 (231.7)	240.8 (268.9)	213.7 (201.7)	186.3 (175)
Day 15	262.7 (273.9)	1.9 (1.9)	2.2 (3.4)	2 (2.7)	327.4 (324.9)	163.3 (115.8)
Week 4	209.7 (221.4)	1.4 (2.5)	1.3 (1.6)	1.4 (2.1)	253.4 (263.9)	143.3 (107.4)
Week 16	125.9 (186.9)	2.6 (3.6)	2 (3.8)	2.3 (3.7)	154.3 (222.2)	74.7 (75.3)
Week 32	116.6 (154.3)	7.8 (25.8)	2.1 (2.7)	5.1 (18.8)	141.2 (172.5)	68.5 (96.8)
Week 48	110 (114.3)	11.7 (43.6)	2.6 (8.9)	7.3 (32.2)	134.9 (123.3)	61.3 (75)
Day 1 Pre-infusion	203.5 (191.4)	256.3 (300.2)	222.8 (230.2)	240 (268)	213.7 (201.7)	186.3 (175)
Day 1 Post-infusion	103.1 (115.1)	11.1 (28.6)	5.7 (8.5)	8.4 (21.3)	102.4 (114.3)	104.3 (118.6)
Day 15 Pre-infusion	264.4 (276.6)	1.9 (1.9)	2.1 (3.3)	2 (2.7)	322.5 (323.5)	164.5 (118)
Day 15 Post-infusion	91.2 (109.2)	1 (1.3)	0.9 (1.4)	0.9 (1.3)	106.3 (130.8)	65.8 (50.4)
Week 16 Pre-infusion	127.8 (190.1)	2.5 (3.3)	2.1 (3.9)	2.3 (3.6)	156.5 (226.3)	76.3 (76.5)
Week 16 Post-infusion	52.7 (72.6)	1.2 (1.6)	0.8 (1)	1 (1.3)	64.2 (83)	30.9 (40.2)
Week 32 Pre-infusion	125 (161.1)	5.1 (16.5)	2 (2.7)	3.6 (11.8)	153.4 (180.6)	72.2 (100.4)
Week 32 Post-infusion	46.2 (54.4)	1 (1.5)	0.7 (1.4)	0.9 (1.4)	56.9 (62.5)	27.6 (29.5)

17. Secondary Outcome

Title	Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL)
Description	CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. 0 represents 0% of participants.
Time Frame	Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Outcome Measure Data

Analysis Population Description

N = number of participants analyzed at the specified visit

Arm/Group Title	Placebo + SOC	OCR 400 mg + SOC	OCR 1000 mg + SOC	OCR + SOC	Placebo-Mycophenolate Mofetil (MMF)	Placebo-Euro Lupus (EL)
Arm/Group Description	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Measure Participants	75	75	73	148	47	28
Baseline	4.3 3.4%	4.2 3.3%	1.5 1.2%	2.9 0.8%	6.8 NaN	0 NaN
Day 15	4.5 3.5%	100 78.1%	97.1 77.1%	98.6 25.9%	7.5 NaN	0 NaN
Week 4	4.4 3.5%	98.5 77%	100 79.4%	99.3 26.1%	7.3 NaN	0 NaN
Week 16	4.3 3.4%	95.8 74.8%	97.1 77.1%	96.5 25.3%	6.7 NaN	0 NaN
Week 32	7.4 5.8%	91.8 71.7%	95.6 75.9%	93.6 24.6%	8.9 NaN	4.3 NaN
Week 48	5.9 4.6%	88.7 69.3%	98.5 78.2%	93.4 24.5%	4.4 NaN	8.7 NaN
Day 1 Pre-infusion	4.3 3.4%	4.2 3.3%	1.5 1.2%	2.9 0.8%	6.8 NaN	0 NaN
Day 1 Post-infusion	10 7.9%	81.2 63.4%	83.8 66.5%	82.5 21.7%	14 NaN	3.7 NaN
Day 15 Pre-infusion	4.4 3.5%	100 78.1%	97.1 77.1%	98.6 25.9%	7 NaN	0 NaN
Day 15 Post-infusion	7.5 5.9%	100 78.1%	100 79.4%	100 26.2%	11.9 NaN	0 NaN
Week 16 Pre-infusion	4.5 3.5%	97 75.8%	97 77%	97 25.5%	7 NaN	0 NaN
Week 16 Post-infusion	11.5 9.1%	100 78.1%	100 79.4%	100 26.2%	12.5 NaN	9.5 NaN
Week 32 Pre-infusion	3.3 2.6%	93.7 73.2%	95.2 75.6%	94.4 24.8%	5.1 NaN	0 NaN
Week 32 Post-infusion	15 11.8%	100 78.1%	100 79.4%	100 26.2%	10.5 NaN	22.7 NaN

18. Secondary Outcome

Title	Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit
Description	CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. n = number of participants analyzed at the specified visit. 0 represents 0% of participants.
Time Frame	Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Outcome Measure Data

Analysis Population Description

N = number of participants analyzed at the specified visit

Arm/Group Title	Placebo + SOC	OCR 400 mg + SOC	OCR 1000 mg + SOC	OCR + SOC	Placebo-Mycophenolate Mofetil (MMF)	Placebo-Euro Lupus (EL)
Arm/Group Description	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Measure Participants	75	75	73	148	47	28
Baseline	7.1 5.6%	11.3 8.8%	3 2.4%	7.3 1.9%	11.4 NaN	0 NaN
Day 15	7.6 6%	100 78.1%	98.5 78.2%	99.3 26.1%	10 NaN	3.8 NaN
Week 4	10.3 8.1%	100 78.1%	100 79.4%	100 26.2%	12.2 NaN	7.4 NaN
Week 16	11.4 9%	98.6 77%	98.6 78.3%	98.6 25.9%	13.3 NaN	8 NaN
Week 32	13.2 10.4%	93.2 72.8%	100 79.4%	96.5 25.3%	15.6 NaN	8.7 NaN
Week 48	17.6 13.9%	91.5 71.5%	98.5 78.2%	94.9 24.9%	13.3 NaN	26.1 NaN
Day 1 Pre-infusion	7.1 5.6%	11.3 8.8%	3 2.4%	7.2 1.9%	11.4 NaN	0 NaN
Day 1 Post-infusion	22.9 18%	87 68%	91.2 72.4%	89.1 23.4%	20.9 NaN	25.9 NaN
Day 15 Pre-infusion	7.4 5.8%	100 78.1%	98.6 78.3%	99.3 26.1%	9.3 NaN	4 NaN
Day 15 Post-infusion	17.9 14.1%	100 78.1%	100 79.4%	100 26.2%	21.4 NaN	12 NaN
Week 16 Pre-infusion	10.4 8.2%	98.5 77%	98.5 78.2%	98.5 25.9%	11.6 NaN	8.3 NaN
Week 16 Post-infusion	41 32.3%	100 78.1%	100 79.4%	100 26.2%	32.5 NaN	57.1 NaN
Week 32 Pre-infusion	8.3 6.5%	95.2 74.4%	100 79.4%	97.6 25.6%	10.3 NaN	4.8 NaN
Week 32 Post-infusion	35 27.6%	100 78.1%	100 79.4%	100 26.2%	26.3 NaN	50 NaN

19. Secondary Outcome

Title	Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit
Description	CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. <LLN = 80 cells/uL.
Time Frame	Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Outcome Measure Data

Analysis Population Description

N = number of participants analyzed at the specified visit

Arm/Group Title	Placebo + SOC	OCR 400 mg + SOC	OCR 1000 mg + SOC	OCR + SOC	Placebo-Mycophenolate Mofetil (MMF)	Placebo-Euro Lupus (EL)
Arm/Group Description	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Measure Participants	70	73	70	141	45	27
Baseline	27.1 21.3%	36.6 28.6%	33.3 26.4%	35 9.2%	29.5 NaN	23.1 NaN
Day 15	28.8 22.7%	100 78.1%	100 79.4%	100 26.2%	30 NaN	26.9 NaN
Week 4	39.7 31.3%	100 78.1%	100 79.4%	100 26.2%	39 NaN	40.7 NaN
Week 16	57.1 45%	100 78.1%	100 79.4%	100 26.2%	48.9 NaN	72 NaN
Week 32	52.9 41.7%	97.3 76%	100 79.4%	98.6 25.9%	35.6 NaN	87 NaN
Week 48	51.5 40.6%	97.2 75.9%	100 79.4%	98.5 25.9%	37.8 NaN	78.3 NaN
Day 1 Pre-infusion	27.1 21.3%	36.6 28.6%	32.8 26%	34.8 9.1%	29.5 NaN	23.1 NaN
Day 1 Post-infusion	55.7 43.9%	97.1 75.9%	100 79.4%	98.5 25.9%	.5 NaN	59.3 NaN
Day 15 Pre-infusion	30.0 23.6%	100 78.1%	100 79.4%	100 26.2%	32.6 NaN	28 NaN
Day 15 Post-infusion	58.2 45.8%	100 78.1%	100 79.4%	100 26.2%	52.4 NaN	68 NaN
Week 16 Pre-infusion	56.7 44.6%	100 78.1%	100 79.4%	100 26.2%	48.8 NaN	70.8 NaN
Week 16 Post-infusion	80.3 63.2%	100 78.1%	100 79.4%	100 26.2%	72.5 NaN	95.2 NaN
Week 32 Pre-infusion	50 39.4%	98.4 76.9%	100 79.4%	99.2 26%	30.8 NaN	85.7 NaN
Week 32 Post-infusion	88.3 69.5%	100 78.1%	100 79.4%	100 26.2%	84.2 NaN	95.5 NaN

20. Secondary Outcome

Title	Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response
Description	A major clinical response was defined as British Isles Lupus Assessment Group (BILAG) C scores or better at Week 24 without developing any new A or two new B scores up to Week 24 and maintenance of this response without developing a moderate or severe flare between Week 24 and Week 48. A partial clinical response was defined as BILAG C scores or better at Week 24 and maintaining this response without developing a flare for 16 consecutive weeks. The BILAG is an organ-specific 86-question assessment based on the principle of the doctor's intent to treat, which requires an assessment of improved (1), the same (2), worse (3), or new (4) over the last month. Within each organ system, multiple manifestations and laboratory tests are combined into a single score for that organ. The resulting scores for each organ can be A through E, where A is very active disease, B is moderate activity, C is mild stable disease, D is resolved activity, and E indicates the organ was never involved.
Time Frame	Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Outcome Measure Data

Analysis Population Description

Efficacy date were summarized in the primary endpoints and due to early study termination the protocol was modified to transition the participants into the safety follow-up period. Additional efficacy outcome measures were not analyzed and study results focus on the full summary of safety data.

Arm/Group Title	OCR 400 mg + SOC	OCR 1000 mg + SOC	Placebo + SOC
Arm/Group Description	Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
Measure Participants	0	0	0

Adverse Events

Time Frame	Baseline up to 19 months.
Adverse Event Reporting Description	All patients who received any part of an infusion of study drug and provided at least one assessment of safety were included in the safety analysis.
Arm/Group Title	Placebo + SOC		OCR 1000 mg + SOC		OCR 400 mg + SOC
Arm/Group Description	Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.		Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.		Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
All Cause Mortality
	Placebo + SOC		OCR 1000 mg + SOC		OCR 400 mg + SOC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/125 (4.8%)		6/127 (4.7%)		3/126 (2.4%)
Serious Adverse Events
	Placebo + SOC		OCR 1000 mg + SOC		OCR 400 mg + SOC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/125 (28.8%)		38/127 (29.9%)		53/126 (42.1%)
Blood and lymphatic system disorders
Agranulocytosis	0/125 (0%)	0	3/127 (2.4%)	3	1/126 (0.8%)	1
Anaemia	1/125 (0.8%)	1	0/127 (0%)	0	3/126 (2.4%)	3
Anaemia of chronic disease	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Antiphospholipid syndrome	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Disseminated intravascular coagulation	0/125 (0%)	0	0/127 (0%)	0	2/126 (1.6%)	2
Febrile neutropenia	0/125 (0%)	0	1/127 (0.8%)	1	2/126 (1.6%)	2
Iron deficiency anaemia	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Leukopenia	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Neutropenia	1/125 (0.8%)	1	5/127 (3.9%)	5	2/126 (1.6%)	2
Cardiac disorders
Acute myocardial infarction	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Cardiac failure	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Cardiac failure congestive	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Cardio-respiratory arrest	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Myocardial infarction	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Pleuropericarditis	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Stress cardiomyopathy	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/125 (0.8%)	2	1/127 (0.8%)	1	0/126 (0%)	0
Ascites	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Diarrhoea	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Enteritis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Gastrointestinal haemorrhage	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Nausea	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Rectal haemorrhage	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Rectal ulcer	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Stomatitis	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
General disorders
Adverse drug reaction	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Chest pain	2/125 (1.6%)	2	0/127 (0%)	0	0/126 (0%)	0
Generalised oedema	0/125 (0%)	0	0/127 (0%)	0	2/126 (1.6%)	2
Polyserositis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Pyrexia	2/125 (1.6%)	2	0/127 (0%)	0	0/126 (0%)	0
Hepatobiliary disorders
Hepatitis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Infections and infestations
Abscess	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Abscess limb	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Appendicitis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Arthritis bacterial	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Bacterial sepsis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Bronchitis	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Bronchopneumonia	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Cellulitis	1/125 (0.8%)	1	2/127 (1.6%)	3	5/126 (4%)	5
Diverticulitis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Ear infection	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Enteritis infectious	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Erysipelas	3/125 (2.4%)	3	0/127 (0%)	0	0/126 (0%)	0
Gastroenteritis	1/125 (0.8%)	2	0/127 (0%)	0	0/126 (0%)	0
Gastroenteritis viral	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Gastrointestinal infection	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	11
H1N1 influenza	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Haematoma infection	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Herpes virus infection	0/125 (0%)	0	1/127 (0.8%)	1	1/126 (0.8%)	1
Herpes zoster	0/125 (0%)	0	3/127 (2.4%)	3	1/126 (0.8%)	1
Herpes zoster disseminated	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Impetigo	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Infection	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Laryngitis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Legionella infection	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Lung infection	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Neurocryptococcosis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Neutropenic infection	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Neutropenic sepsis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Pneumocystis jirovecii pneumonia	0/125 (0%)	0	1/127 (0.8%)	1	1/126 (0.8%)	1
Pneumonia	2/125 (1.6%)	2	8/127 (6.3%)	8	4/126 (3.2%)	5
Pneumonia cytomegaloviral	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Pseudomembranous colitis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Pyelonephritis	0/125 (0%)	0	1/127 (0.8%)	1	2/126 (1.6%)	2
Pyoderma	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Respiratory tract infection	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Salmonella bacteraemia	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Salmonella sepsis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Sepsis	1/125 (0.8%)	1	1/127 (0.8%)	1	2/126 (1.6%)	3
Septic shock	0/125 (0%)	0	1/127 (0.8%)	1	1/126 (0.8%)	1
Skin infection	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Staphylococcal bacteraemia	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Strongyloidiasis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Tuberculosis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Upper respiratory tract infection	0/125 (0%)	0	2/127 (1.6%)	2	0/126 (0%)	0
Urosepsis	0/125 (0%)	0	2/127 (1.6%)	2	0/126 (0%)	0
Sinusitis	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Urinary Tract Infection	1/125 (0.8%)	1	2/127 (1.6%)	2	4/126 (3.2%)	6
Injury, poisoning and procedural complications
Infusion related reaction	0/125 (0%)	0	1/127 (0.8%)	1	1/126 (0.8%)	1
Joint dislocation	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Thermal burn	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Investigations
Blood creatine increased	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Weight increased	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Metabolism and nutrition disorders
Diabetes mellitus	0/125 (0%)	0	0/127 (0%)	0	2/126 (1.6%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Muscle contracture	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Osteonecrosis	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Systemic lupus erythematosus	3/125 (2.4%)	3	2/127 (1.6%)	5	3/126 (2.4%)	7
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Anogenital warts	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Cervix carcinoma	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Gastric cancer	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Rectal adenoma	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Renal cell carcinoma	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Nervous system disorders
Cerebral haemorrhage	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Cerebral infarction	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Cerebrovascular accident	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Cerebrovascular disorder	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Convulsion	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Headache	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Ischaemic stroke	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Lupus encephalitis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Migraine	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Vasculitis cerebral	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion missed	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Gestational hypertension	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Psychiatric disorders
Depression	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Suicide attempt	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Renal and urinary disorders
Lupus nephritis	2/125 (1.6%)	3	0/127 (0%)	0	1/126 (0.8%)	1
Nephritis	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Nephrotic syndrome	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Proteinuria	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Renal disorder	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Renal failure	2/125 (1.6%)	2	1/127 (0.8%)	2	1/126 (0.8%)	1
Renal failure acute	0/125 (0%)	0	1/127 (0.8%)	1	2/126 (1.6%)	2
Renal failure chronic	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Tubulointerstitial nephritis	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Urinary bladder haemorrhage	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Reproductive system and breast disorders
Amenorrhoea	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Cervical dysplasia	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Ovarian cyst	0/125 (0%)	0	1/127 (0.8%)	1	1/126 (0.8%)	1
Ovarian mass	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/125 (0.8%)	1	0/127 (0%)	0	1/126 (0.8%)	1
Dyspnoea	1/125 (0.8%)	1	0/127 (0%)	0	0/126 (0%)	0
Pulmonary embolism	1/125 (0.8%)	1	0/127 (0%)	0	2/126 (1.6%)	2
Pulmonary oedema	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	0/125 (0%)	0	0/127 (0%)	0	1/126 (0.8%)	1
Vascular disorders
Deep vein thrombosis	0/125 (0%)	0	1/127 (0.8%)	1	1/126 (0.8%)	1
Hypertension	0/125 (0%)	0	1/127 (0.8%)	1	0/126 (0%)	0
Malignant hypertension	1/125 (0.8%)		0/127 (0%)	0	0/126 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo + SOC		OCR 1000 mg + SOC		OCR 400 mg + SOC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/125 (76.8%)		91/127 (71.7%)		101/126 (80.2%)
Blood and lymphatic system disorders
Anaemia	5/125 (4%)	5	7/127 (5.5%)	7	13/126 (10.3%)	17
Leukopenia	7/125 (5.6%)	11	12/127 (9.4%)	17	18/126 (14.3%)	24
Neutropenia	6/125 (4.8%)	7	7/127 (5.5%)	10	15/126 (11.9%)	27
Gastrointestinal disorders
Abdominal pain	3/125 (2.4%)	3	7/127 (5.5%)	8	5/126 (4%)	5
Diarrhoea	22/125 (17.6%)	29	32/127 (25.2%)	36	26/126 (20.6%)	35
Dyspepsia	4/125 (3.2%)	5	3/127 (2.4%)	3	9/126 (7.1%)	10
Gastritis	2/125 (1.6%)	2	2/127 (1.6%)	3	11/126 (8.7%)	15
Nausea	7/125 (5.6%)	7	4/127 (3.1%)	5	13/126 (10.3%)	16
Vomiting	7/125 (5.6%)	7	4/127 (3.1%)	4	11/126 (8.7%)	11
General disorders
Oedema peripheral	8/125 (6.4%)	9	4/127 (3.1%)	4	2/126 (1.6%)	5
Pyrexia	1/125 (0.8%)	1	2/127 (1.6%)	3	7/126 (5.6%)	7
Infections and infestations
Bronchitis	10/125 (8%)	16	10/127 (7.9%)	12	14/126 (11.1%)	17
Gastroenteritis	10/125 (8%)	11	4/127 (3.1%)	4	7/126 (5.6%)	10
Herpes zoster	6/125 (4.8%)	6	9/127 (7.1%)	11	8/126 (6.3%)	9
Nasopharyngitis	16/125 (12.8%)	23	13/127 (10.2%)	20	17/126 (13.5%)	24
Oral candidiasis	1/125 (0.8%)	1	1/127 (0.8%)	1	7/126 (5.6%)	10
Pharyngitis	4/125 (3.2%)	4	7/127 (5.5%)	7	13/126 (10.3%)	13
Sinusitis	3/125 (2.4%)	4	7/127 (5.5%)	12	3/126 (2.4%)	5
Upper respiratory tract infection	19/125 (15.2%)	28	23/127 (18.1%)	43	22/126 (17.5%)	42
Urinary tract infection	13/125 (10.4%)	13	18/127 (14.2%)	35	24/126 (19%)	43
Injury, poisoning and procedural complications
Infusion related reaction	11/125 (8.8%)	12	17/127 (13.4%)	19	14/126 (11.1%)	18
Metabolism and nutrition disorders
Dyslipidaemia	11/125 (8.8%)	14	2/127 (1.6%)	2	5/126 (4%)	5
Hypokalaemia	9/125 (7.2%)	12	4/127 (3.1%)	4	9/126 (7.1%)	16
Musculoskeletal and connective tissue disorders
Arthralgia	5/125 (4%)	5	6/127 (4.7%)	8	7/126 (5.6%)	9
Back pain	6/125 (4.8%)	6	8/127 (6.3%)	8	6/126 (4.8%)	8
Muscle spasms	7/125 (5.6%)	7	4/127 (3.1%)	4	8/126 (6.3%)	8
Nervous system disorders
Dizziness	9/125 (7.2%)	9	5/127 (3.9%)	6	6/126 (4.8%)	6
Headache	11/125 (8.8%)	18	11/127 (8.7%)	12	15/126 (11.9%)	21
Psychiatric disorders
Insomnia	3/125 (2.4%)	4	7/127 (5.5%)	7	7/126 (5.6%)	7
Respiratory, thoracic and mediastinal disorders
Cough	7/125 (5.6%)	8	4/127 (3.1%)	5	11/126 (8.7%)	12
Skin and subcutaneous tissue disorders
Alopecia	8/125 (6.4%)	8	1/127 (0.8%)	1	3/126 (2.4%)	3
Vascular disorders
Hypertension	7/125 (5.6%)	8	12/127 (9.4%)	15	12/126 (9.5%)	19

Limitations/Caveats

The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated participants versus placebo-treated participants. Only 139 of the 381 participants randomized completed the 48 week treatment period.

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Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.