Trial Outcomes & Findings for A Study to Evaluate Ocrelizumab in Patients With Nephritis Due to Systemic Lupus Erythematosus (BELONG) (NCT NCT00626197)

Last Updated: 2020-12-22

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

381 participants

Primary outcome timeframe

Week 48

Results posted on

2020-12-22

Participant Flow

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

Participant milestones

Participant milestones
Measure	OCR 400 mg + SOC 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.	OCR 1000 mg + SOC 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.	Placebo + SOC 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.
Overall Study STARTED	127	128	126
Overall Study COMPLETED	83	74	49
Overall Study NOT COMPLETED	44	54	77

Reasons for withdrawal

Reasons for withdrawal
Measure	OCR 400 mg + SOC 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.	OCR 1000 mg + SOC 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.	Placebo + SOC 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.
Overall Study Did not cooperate	2	6	1
Overall Study Failure to return	6	5	6
Overall Study Adverse event, serious fatal	3	6	6
Overall Study Adverse Event	1	1	2
Overall Study Withdrawal by Subject	17	17	7
Overall Study Administrative reasons	15	19	55

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OCR 400 mg + SOC n=127 Participants 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.	OCR 1000 mg + SOC n=128 Participants 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.	Placebo + SOC n=126 Participants 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 n=381 Participants Total of all reporting groups
Age, Continuous	31.9 Years STANDARD_DEVIATION 10.2 • n=5 Participants	30.6 Years STANDARD_DEVIATION 8.9 • n=7 Participants	31.3 Years STANDARD_DEVIATION 9.9 • n=5 Participants	31.3 Years STANDARD_DEVIATION 9.7 • n=4 Participants
Sex: Female, Male Female	115 Participants n=5 Participants	110 Participants n=7 Participants	107 Participants n=5 Participants	332 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	49 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	17 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants	49 Participants n=4 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	27 Participants n=7 Participants	35 Participants n=5 Participants	101 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=4 Participants
Race (NIH/OMB) White	55 Participants n=5 Participants	67 Participants n=7 Participants	58 Participants n=5 Participants	180 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	32 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 48

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

Outcome measures

Outcome measures
Measure	OCR 400 mg + SOC n=75 Participants 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.	OCR 1000 mg + SOC n=73 Participants 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.	Placebo + SOC n=75 Participants 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.	OCR + SOC This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo-Mycophenolate Mofetil (MMF) Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-Euro Lupus (EL) Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Number of Participants Who Achieved Complete Renal Response (CRR) CRR	42.7 Percentage of Participants	31.5 Percentage of Participants	34.7 Percentage of Participants	—	—	—
Number of Participants Who Achieved Complete Renal Response (CRR) PRR	24 Percentage of Participants	35.6 Percentage of Participants	20 Percentage of Participants	—	—	—

PRIMARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Outcome measures
Measure	OCR 400 mg + SOC n=75 Participants 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.	OCR 1000 mg + SOC n=73 Participants 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.	Placebo + SOC n=75 Participants 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.	OCR + SOC This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo-Mycophenolate Mofetil (MMF) Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-Euro Lupus (EL) Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Percentage of Participants Who Achieved Overall Response	66.7 Percentage of Participants Interval 56.0 to 77.3	67.1 Percentage of Participants Interval 56.3 to 77.9	54.7 Percentage of Participants Interval 43.4 to 65.9	—	—	—

SECONDARY outcome

Timeframe: Weeks 36, 40, 44, and 48

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 12, 24, 36, and 48

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 12, 24, 36, and 48

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

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 1, 24, and 48

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Population: N = number of participants analyzed at the specified visit

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).

Outcome measures

Outcome measures
Measure	OCR 400 mg + SOC n=75 Participants 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.	OCR 1000 mg + SOC n=73 Participants 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.	Placebo + SOC n=70 Participants 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.	OCR + SOC n=141 Participants This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo-Mycophenolate Mofetil (MMF) n=45 Participants Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-Euro Lupus (EL) n=27 Participants Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 16 Pre-infusion	127.8 Cells/uL Standard Deviation 190.1	2.5 Cells/uL Standard Deviation 3.3	2.1 Cells/uL Standard Deviation 3.9	2.3 Cells/uL Standard Deviation 3.6	156.5 Cells/uL Standard Deviation 226.3	76.3 Cells/uL Standard Deviation 76.5
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Day 1 Pre-infusion	203.5 Cells/uL Standard Deviation 191.4	256.3 Cells/uL Standard Deviation 300.2	222.8 Cells/uL Standard Deviation 230.2	240 Cells/uL Standard Deviation 268	213.7 Cells/uL Standard Deviation 201.7	186.3 Cells/uL Standard Deviation 175
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Day 1 Post-infusion	103.1 Cells/uL Standard Deviation 115.1	11.1 Cells/uL Standard Deviation 28.6	5.7 Cells/uL Standard Deviation 8.5	8.4 Cells/uL Standard Deviation 21.3	102.4 Cells/uL Standard Deviation 114.3	104.3 Cells/uL Standard Deviation 118.6
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Baseline	203.5 Cells/uL Standard Deviation 191.4	256.3 Cells/uL Standard Deviation 300.2	224.1 Cells/uL Standard Deviation 231.7	240.8 Cells/uL Standard Deviation 268.9	213.7 Cells/uL Standard Deviation 201.7	186.3 Cells/uL Standard Deviation 175
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Day 15	262.7 Cells/uL Standard Deviation 273.9	1.9 Cells/uL Standard Deviation 1.9	2.2 Cells/uL Standard Deviation 3.4	2 Cells/uL Standard Deviation 2.7	327.4 Cells/uL Standard Deviation 324.9	163.3 Cells/uL Standard Deviation 115.8
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 4	209.7 Cells/uL Standard Deviation 221.4	1.4 Cells/uL Standard Deviation 2.5	1.3 Cells/uL Standard Deviation 1.6	1.4 Cells/uL Standard Deviation 2.1	253.4 Cells/uL Standard Deviation 263.9	143.3 Cells/uL Standard Deviation 107.4
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Day 15 Pre-infusion	264.4 Cells/uL Standard Deviation 276.6	1.9 Cells/uL Standard Deviation 1.9	2.1 Cells/uL Standard Deviation 3.3	2 Cells/uL Standard Deviation 2.7	322.5 Cells/uL Standard Deviation 323.5	164.5 Cells/uL Standard Deviation 118
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Day 15 Post-infusion	91.2 Cells/uL Standard Deviation 109.2	1 Cells/uL Standard Deviation 1.3	0.9 Cells/uL Standard Deviation 1.4	0.9 Cells/uL Standard Deviation 1.3	106.3 Cells/uL Standard Deviation 130.8	65.8 Cells/uL Standard Deviation 50.4
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 16	125.9 Cells/uL Standard Deviation 186.9	2.6 Cells/uL Standard Deviation 3.6	2 Cells/uL Standard Deviation 3.8	2.3 Cells/uL Standard Deviation 3.7	154.3 Cells/uL Standard Deviation 222.2	74.7 Cells/uL Standard Deviation 75.3
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 16 Post-infusion	52.7 Cells/uL Standard Deviation 72.6	1.2 Cells/uL Standard Deviation 1.6	0.8 Cells/uL Standard Deviation 1	1 Cells/uL Standard Deviation 1.3	64.2 Cells/uL Standard Deviation 83	30.9 Cells/uL Standard Deviation 40.2
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 32 Pre-infusion	125 Cells/uL Standard Deviation 161.1	5.1 Cells/uL Standard Deviation 16.5	2 Cells/uL Standard Deviation 2.7	3.6 Cells/uL Standard Deviation 11.8	153.4 Cells/uL Standard Deviation 180.6	72.2 Cells/uL Standard Deviation 100.4
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 32	116.6 Cells/uL Standard Deviation 154.3	7.8 Cells/uL Standard Deviation 25.8	2.1 Cells/uL Standard Deviation 2.7	5.1 Cells/uL Standard Deviation 18.8	141.2 Cells/uL Standard Deviation 172.5	68.5 Cells/uL Standard Deviation 96.8
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 48	110 Cells/uL Standard Deviation 114.3	11.7 Cells/uL Standard Deviation 43.6	2.6 Cells/uL Standard Deviation 8.9	7.3 Cells/uL Standard Deviation 32.2	134.9 Cells/uL Standard Deviation 123.3	61.3 Cells/uL Standard Deviation 75
Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells Per Visit Week 32 Post-infusion	46.2 Cells/uL Standard Deviation 54.4	1 Cells/uL Standard Deviation 1.5	0.7 Cells/uL Standard Deviation 1.4	0.9 Cells/uL Standard Deviation 1.4	56.9 Cells/uL Standard Deviation 62.5	27.6 Cells/uL Standard Deviation 29.5

SECONDARY outcome

Timeframe: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Population: N = number of participants analyzed at the specified visit

Outcome measures

Outcome measures
Measure	OCR 400 mg + SOC n=75 Participants 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.	OCR 1000 mg + SOC n=75 Participants 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.	Placebo + SOC n=73 Participants 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.	OCR + SOC n=148 Participants This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo-Mycophenolate Mofetil (MMF) n=47 Participants Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-Euro Lupus (EL) n=28 Participants Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 16	4.3 Percentage of Participants	95.8 Percentage of Participants	97.1 Percentage of Participants	96.5 Percentage of Participants	6.7 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Baseline	4.3 Percentage of Participants	4.2 Percentage of Participants	1.5 Percentage of Participants	2.9 Percentage of Participants	6.8 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Day 15	4.5 Percentage of Participants	100 Percentage of Participants	97.1 Percentage of Participants	98.6 Percentage of Participants	7.5 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 4	4.4 Percentage of Participants	98.5 Percentage of Participants	100 Percentage of Participants	99.3 Percentage of Participants	7.3 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 32	7.4 Percentage of Participants	91.8 Percentage of Participants	95.6 Percentage of Participants	93.6 Percentage of Participants	8.9 Percentage of Participants	4.3 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 48	5.9 Percentage of Participants	88.7 Percentage of Participants	98.5 Percentage of Participants	93.4 Percentage of Participants	4.4 Percentage of Participants	8.7 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Day 1 Pre-infusion	4.3 Percentage of Participants	4.2 Percentage of Participants	1.5 Percentage of Participants	2.9 Percentage of Participants	6.8 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Day 1 Post-infusion	10 Percentage of Participants	81.2 Percentage of Participants	83.8 Percentage of Participants	82.5 Percentage of Participants	14 Percentage of Participants	3.7 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Day 15 Pre-infusion	4.4 Percentage of Participants	100 Percentage of Participants	97.1 Percentage of Participants	98.6 Percentage of Participants	7 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Day 15 Post-infusion	7.5 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	11.9 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 16 Pre-infusion	4.5 Percentage of Participants	97 Percentage of Participants	97 Percentage of Participants	97 Percentage of Participants	7 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 16 Post-infusion	11.5 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	12.5 Percentage of Participants	9.5 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 32 Pre-infusion	3.3 Percentage of Participants	93.7 Percentage of Participants	95.2 Percentage of Participants	94.4 Percentage of Participants	5.1 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <10 Cells Per Microliter (Cells/uL) Week 32 Post-infusion	15 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	10.5 Percentage of Participants	22.7 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Population: N = number of participants analyzed at the specified visit

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.

Outcome measures

Outcome measures
Measure	OCR 400 mg + SOC n=75 Participants 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.	OCR 1000 mg + SOC n=75 Participants 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.	Placebo + SOC n=73 Participants 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.	OCR + SOC n=148 Participants This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo-Mycophenolate Mofetil (MMF) n=47 Participants Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-Euro Lupus (EL) n=28 Participants Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Baseline	7.1 Percentage of Participants	11.3 Percentage of Participants	3 Percentage of Participants	7.3 Percentage of Participants	11.4 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Day 15	7.6 Percentage of Participants	100 Percentage of Participants	98.5 Percentage of Participants	99.3 Percentage of Participants	10 Percentage of Participants	3.8 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 4	10.3 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	12.2 Percentage of Participants	7.4 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 16	11.4 Percentage of Participants	98.6 Percentage of Participants	98.6 Percentage of Participants	98.6 Percentage of Participants	13.3 Percentage of Participants	8 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 32	13.2 Percentage of Participants	93.2 Percentage of Participants	100 Percentage of Participants	96.5 Percentage of Participants	15.6 Percentage of Participants	8.7 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 48	17.6 Percentage of Participants	91.5 Percentage of Participants	98.5 Percentage of Participants	94.9 Percentage of Participants	13.3 Percentage of Participants	26.1 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Day 1 Pre-infusion	7.1 Percentage of Participants	11.3 Percentage of Participants	3 Percentage of Participants	7.2 Percentage of Participants	11.4 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Day 1 Post-infusion	22.9 Percentage of Participants	87 Percentage of Participants	91.2 Percentage of Participants	89.1 Percentage of Participants	20.9 Percentage of Participants	25.9 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Day 15 Pre-infusion	7.4 Percentage of Participants	100 Percentage of Participants	98.6 Percentage of Participants	99.3 Percentage of Participants	9.3 Percentage of Participants	4 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Day 15 Post-infusion	17.9 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	21.4 Percentage of Participants	12 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 16 Pre-infusion	10.4 Percentage of Participants	98.5 Percentage of Participants	98.5 Percentage of Participants	98.5 Percentage of Participants	11.6 Percentage of Participants	8.3 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 16 Post-infusion	41 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	32.5 Percentage of Participants	57.1 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 32 Pre-infusion	8.3 Percentage of Participants	95.2 Percentage of Participants	100 Percentage of Participants	97.6 Percentage of Participants	10.3 Percentage of Participants	4.8 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts <20 Cells/uL by Visit Week 32 Post-infusion	35 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	26.3 Percentage of Participants	50 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32

Population: N = number of participants analyzed at the specified visit

Outcome measures

Outcome measures
Measure	OCR 400 mg + SOC n=70 Participants 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.	OCR 1000 mg + SOC n=73 Participants 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.	Placebo + SOC n=70 Participants 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.	OCR + SOC n=141 Participants This analysis set included all participants who were treated with ocrelizumab (OCR).	Placebo-Mycophenolate Mofetil (MMF) n=45 Participants Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.	Placebo-Euro Lupus (EL) n=27 Participants Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 32 Post-infusion	88.3 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	84.2 Percentage of Participants	95.5 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Baseline	27.1 Percentage of Participants	36.6 Percentage of Participants	33.3 Percentage of Participants	35 Percentage of Participants	29.5 Percentage of Participants	23.1 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Day 15	28.8 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	30 Percentage of Participants	26.9 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 4	39.7 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	39 Percentage of Participants	40.7 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 16	57.1 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	48.9 Percentage of Participants	72 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 32	52.9 Percentage of Participants	97.3 Percentage of Participants	100 Percentage of Participants	98.6 Percentage of Participants	35.6 Percentage of Participants	87 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 48	51.5 Percentage of Participants	97.2 Percentage of Participants	100 Percentage of Participants	98.5 Percentage of Participants	37.8 Percentage of Participants	78.3 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Day 1 Pre-infusion	27.1 Percentage of Participants	36.6 Percentage of Participants	32.8 Percentage of Participants	34.8 Percentage of Participants	29.5 Percentage of Participants	23.1 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Day 1 Post-infusion	55.7 Percentage of Participants	97.1 Percentage of Participants	100 Percentage of Participants	98.5 Percentage of Participants	.5 Percentage of Participants	59.3 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Day 15 Pre-infusion	30.0 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	32.6 Percentage of Participants	28 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Day 15 Post-infusion	58.2 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	52.4 Percentage of Participants	68 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 16 Pre-infusion	56.7 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	48.8 Percentage of Participants	70.8 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 16 Post-infusion	80.3 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants	72.5 Percentage of Participants	95.2 Percentage of Participants
Percentage of Participants With CD19+ Absolute B Cell Counts Less Than the Lower Limit of Normal (LLN) by Visit Week 32 Pre-infusion	50 Percentage of Participants	98.4 Percentage of Participants	100 Percentage of Participants	99.2 Percentage of Participants	30.8 Percentage of Participants	85.7 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Placebo + SOC

Serious events: 36 serious events

Other events: 96 other events

Deaths: 6 deaths

OCR 1000 mg + SOC

Serious events: 38 serious events

Other events: 91 other events

Deaths: 6 deaths

OCR 400 mg + SOC

Serious events: 53 serious events

Other events: 101 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

F. Hoffmann-La Roche Ltd/Genentech Inc.

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER