Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With ISN/RPS 2003 Class III or IV Lupus Nephritis (NCT NCT04221477)

Last Updated: 2025-11-06

Results Overview

CRR was defined as an achievement of all the following criteria: urinary protein-to-creatinine ratio (UPCR) \<0.5 gram/gram (g/g); estimated glomerular filtration rate (eGFR) \>=85% of baseline, as calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Obinutuzumab and placebo were compared using Cochran-Mantel-Haenszel (CMH) test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using fully conditional specification (FCS) predicted mean matching method. Percentage have been rounded off.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

271 participants

Primary outcome timeframe

At Week 76

Results posted on

2025-11-06

Participant Flow

A total of 271 participants with International Society of Nephrology/ Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN) treated with standard-of-care (SOC) therapy took part in the study across 72 sites in 15 countries. This study consists of blinded treatment with obinutuzumab or placebo, followed by open-label treatment (OLT) with obinutuzumab.

Participants were randomized in a 1:1 ratio to Obinutuzumab/placebo. As pre-specified in the statistical analysis plan (SAP), participant flow data for all participants randomized to 1 of the 2 dosing schedules of obinutuzumab (Groups 1 \& 2) were reported in the combined obinutuzumab treatment group. This study is ongoing.

Participant milestones

Participant milestones
Measure	Obinutuzumab Participants received obinutuzumab, 1000 milligrams (mg) as an intravenous (IV) infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with mycophenolate mofetil (MMF) and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and every 6 months (Q6M) thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.
Overall Study STARTED	135	136
Overall Study Safety Population	136	132
Overall Study Completed Week 76 Assessment	122	120
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	135	136

Reasons for withdrawal

Reasons for withdrawal
Measure	Obinutuzumab Participants received obinutuzumab, 1000 milligrams (mg) as an intravenous (IV) infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with mycophenolate mofetil (MMF) and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and every 6 months (Q6M) thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.
Overall Study Adverse Event	1	1
Overall Study Death	5	4
Overall Study Lack of Efficacy	1	2
Overall Study Lost to Follow-up	1	2
Overall Study Non-compliance with Study Drug	1	0
Overall Study Reason not Specified	0	5
Overall Study Physician Decision	0	6
Overall Study Withdrawal by Subject	10	14
Overall Study Ongoing in the Study	116	102

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With ISN/RPS 2003 Class III or IV Lupus Nephritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.	Total n=271 Participants Total of all reporting groups
Age, Continuous	33.0 years STANDARD_DEVIATION 10.5 • n=49 Participants	32.7 years STANDARD_DEVIATION 10.0 • n=50 Participants	32.9 years STANDARD_DEVIATION 10.2 • n=50 Participants
Sex: Female, Male Female	114 Participants n=49 Participants	115 Participants n=50 Participants	229 Participants n=50 Participants
Sex: Female, Male Male	21 Participants n=49 Participants	21 Participants n=50 Participants	42 Participants n=50 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	71 Participants n=49 Participants	85 Participants n=50 Participants	156 Participants n=50 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=49 Participants	48 Participants n=50 Participants	102 Participants n=50 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=49 Participants	3 Participants n=50 Participants	13 Participants n=50 Participants
Race (NIH/OMB) American Indian or Alaska Native	25 Participants n=49 Participants	26 Participants n=50 Participants	51 Participants n=50 Participants
Race (NIH/OMB) Asian	9 Participants n=49 Participants	7 Participants n=50 Participants	16 Participants n=50 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=49 Participants	0 Participants n=50 Participants	0 Participants n=50 Participants
Race (NIH/OMB) Black or African American	20 Participants n=49 Participants	20 Participants n=50 Participants	40 Participants n=50 Participants
Race (NIH/OMB) White	65 Participants n=49 Participants	64 Participants n=50 Participants	129 Participants n=50 Participants
Race (NIH/OMB) More than one race	11 Participants n=49 Participants	9 Participants n=50 Participants	20 Participants n=50 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=49 Participants	10 Participants n=50 Participants	15 Participants n=50 Participants

PRIMARY outcome

Timeframe: At Week 76

Population: Efficacy population included all randomized participants regardless of whether they received study drug. As pre-specified in the SAP, all the endpoints were to be compared between the obinutuzumab (combined treatment groups) and placebo groups.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Percentage of Participants With Complete Renal Response (CRR)	46.4 percentage of participants Interval 37.95 to 54.86	33.1 percentage of participants Interval 25.18 to 41.0

SECONDARY outcome

Timeframe: At Week 76

CRR with successful prednisone was defined as the achievement of CRR at Week 76 with no receipt of prednisone \>7.5 milligrams per day (mg/day) (or equivalent) from Week 64 through Week 76. CRR was defined as achievement of all the following criteria: UPCR \<0.5 g/g; eGFR \>=85% of baseline, as calculated using the CKD-EPI equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentage have been rounded off.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Percentage of Participants Who Achieve CRR With Successful Prednisone Taper at Week 76	42.7 percentage of participants Interval 34.32 to 51.09	30.9 percentage of participants Interval 23.12 to 38.65

SECONDARY outcome

Timeframe: At Week 76

Proteinuric response was defined as an achievement of all the following criteria: UPCR \<0.8 g/g and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentage have been rounded off.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Percentage of Participants Who Achieve a Proteinuric Response	55.5 percentage of participants Interval 47.09 to 63.95	41.9 percentage of participants Interval 33.62 to 50.2

SECONDARY outcome

Timeframe: At Week 76

Change in eGFR from baseline to Week 76 was analyzed using Analysis of Covariance (ANCOVA) model with covariates baseline eGFR and the stratification factors race and region. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with 0. Missing data was imputed by multiple imputations using FCS predicted mean matching method. mL/min/1.73 m\^2 = milliliters per minute per 1.73 square meters. Adjusted mean has been reported.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Mean Change in eGFR	2.31 mL/min/1.73 m^2 Standard Error 2.713	-1.54 mL/min/1.73 m^2 Standard Error 2.706

SECONDARY outcome

Timeframe: From Day 1 to Week 76

Percentage of participants with death or renal-related events were defined as participants with one or more of the following events: Death; Treatment failure; Worsening proteinuria, defined as a confirmed ≥50% increase in UPCR to a value ≥3 g/g; Worsening eGFR, defined as a confirmed ≥30% decrease in eGFR to a value \<60. Early study withdrawal due to lack of efficacy was an intercurrent event. Participants experiencing the intercurrent event were considered as participants with events under composite strategy. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Percentage of Participants Who Experience Death or Renal-related Events	18.9 percentage of participants Interval 12.11 to 25.61	35.6 percentage of participants Interval 27.5 to 43.78

SECONDARY outcome

Timeframe: At Week 50

ORR was defined as achievement of either CRR or PRR. CRR was defined as achievement of all of the criteria: UPCR \<0.5 g/g; eGFR ≥85% of baseline, as calculated using the CKD-EPI equation. PRR was defined as achievement of all of the following criteria: ≥50% reduction in UPCR from baseline; UPCR \<1 g/g (or \<3 g/g if the baseline UPCR was ≥3 g/g); eGFR ≥85% of baseline, as calculated using the CKD-EPI equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentage have been rounded off.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Percentage of Participants Who Achieve an Overall Renal Response (ORR)	59.1 percentage of participants Interval 50.8 to 67.43	50.7 percentage of participants Interval 42.16 to 59.22

SECONDARY outcome

Timeframe: At Week 76

The FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The sum of all responses resulted in the FACIT-F score of 0 (worse score) to 52 (better score). Higher scores indicate less fatigue. Change in FACIT-F score from baseline at Week 76 was analyzed using ANCOVA model with covariates baseline FACIT-F score and the stratification factors race and region. Death was considered as an intercurrent event which was handled under composite strategy by imputing FACIT-F score after death with 0. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Adjusted mean has been reported.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Change From Baseline in Fatigue Assessed Using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale	1.76 score on a scale Standard Error 1.223	3.11 score on a scale Standard Error 1.212

SECONDARY outcome

Timeframe: At Week 50

Anti-dsDNA are types of autoantibodies produced by the immune system and are indicators of lupus. Anti-dsDNA data was log-transformed before analysis. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Analysis was performed using ANCOVA. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with upper limit of quantification (ULOQ, 890 international units/milliliter \[IU/mL\]). Adjusted mean has been reported.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Change in Log-transformed Anti-double-stranded Deoxyribonucleic Acid (Anti-dsDNA) Titer	-0.38 Log (IU/mL) Standard Error 0.100	-0.01 Log (IU/mL) Standard Error 0.099

SECONDARY outcome

Timeframe: At Week 50

C3 is a marker of inflammation. Analysis was performed using ANCOVA. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with lower limit of quantification (LLOQ)/2 under composite strategy. LLOQ at the central lab was set for C3 at 0.100 grams/liters (g/L). Missing data was imputed by multiple imputations using FCS predicted mean matching method. Adjusted mean has been reported.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Change in Complement C3	0.20 g/L Standard Error 0.030	0.06 g/L Standard Error 0.030

SECONDARY outcome

Timeframe: At Week 76

The SLEDAI-2K is a 24-item instrument that evaluates clinical symptoms and laboratory markers across nine organ systems and was used to capture changes in lupus-related disease activity. SLE manifestations are assessed by the clinician if present within the last 30 days and added to determine the total SLEDAI-2K score, which ranges from 0 to 105. Higher scores indicate increased disease activity. The analysis was performed using ANCOVA. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with 105, the highest possible score. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Adjusted mean has been reported.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)	-5.63 score on a scale Standard Error 1.456	-5.51 score on a scale Standard Error 1.432

SECONDARY outcome

Timeframe: From baseline (Day 1) up to 80.3 weeks

CRR was defined as an achievement of all the following criteria: UPCR \<0.5 g/g; eGFR \>=85% of baseline, as calculated using the CKD-EPI equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Participants who experienced the intercurrent events before achieving CRR as well as participants who completed 76-week treatment period without experiencing CRR were censored at Week 76. Summary statistics of time to onset of CRR are Kaplan-Meier estimates. A log-rank test was used to compare obinutuzumab and placebo. The median time to onset of CRR was greater than Week 76 due to considering the upper limit of the Week 76 analysis visit window in this analysis. The upper limit of the Week 76 visit window was 3 days prior to the next obinutuzumab or placebo infusion or 30 days beyond Week 76 whichever is shorter.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Time to Onset of CRR	76.4 weeks Interval 76.1 to 77.4	80.3 weeks Interval 76.3 to Upper limit of 95% CI was not estimable due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: At Week 76

CRR with serum creatinine criteria was defined as achievement of all the following criteria: UPCR \<0.5 g/g; Serum creatinine ≤ ULN, as determined by the central laboratory; serum creatinine not increased from baseline by \> 25% and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Percentage have been rounded off.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=135 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=136 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Percentage of Participants Who Achieve CRR With Serum Creatinine Criteria	46.4 percentage of participants Interval 37.9 to 54.85	33.1 percentage of participants Interval 25.18 to 41.0

SECONDARY outcome

Timeframe: Up to Week 76

Population: Safety evaluable population included all participants who received any part of blinded infusion of obinutuzumab or placebo and were grouped according to the treatment they actually received rather than the treatment assigned. As pre-specified in the SAP, safety data were to be provided for obinutuzumab (combined treatment groups) and placebo groups.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Outcome measures

Outcome measures
Measure	Obinutuzumab n=136 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=132 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Number of Participants With Adverse Events (AEs)	126 Participants	117 Participants

SECONDARY outcome

Timeframe: Up to Week 76

An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable \& unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms, or disease temporally associated with use of pharmaceutical product, whether or not considered related to product. AESIs included potential drug-induced liver injury that include an elevated alanine transaminase (ALT) \& aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice defined by Hy's law; suspected transmission of an infectious agent by study drug; infusion-related reactions (IRRs); grade 3/higher infections; any hepatitis B reactivation and progressive multifocal leukoencephalopathy (PML); drug-related neutropenia; drug-related thrombocytopenia; gastrointestinal perforations and worsening of pre-existing cardiac conditions

Outcome measures

Outcome measures
Measure	Obinutuzumab n=136 Participants Participants received obinutuzumab, 1000 mg as an IV infusion on Day 1 and Weeks 2, 24, 26, and either Weeks 50 and 52 or Week 52 only, along with MMF and SOC therapy. Placebo was administered at Week 50 for participants not treated with obinutuzumab. Participants with adequate response at Week 76 continued to receive obinutuzumab at Week 80 and Q6M thereafter. The dose of MMF can be adjusted at the investigator's discretion beginning at Week 80.	Placebo n=132 Participants Participants received Obinutuzumab matching placebo as an IV infusion on Day 1 and Weeks 2, 24, 26, 50, and 52. Participants also received SOC therapy and MMF. Participants with adequate response at Week 76 continued to receive placebo at Week 80 and Q6M thereafter.
Number of Participants With Adverse Events of Special Interest (AESIs) IRRs	21 Participants	15 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Grade 3-5 infection	21 Participants	9 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Any Hepatitis B reactivation and PML	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Drug related Neutropenia	17 Participants	5 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Drug related Thrombocytopenia	1 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Gastrointestinal Perforations	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Worsening of pre-existing Cardiac Conditions	0 Participants	2 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Hy's Law	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESIs) Suspected Transmission of an Infectious Agent by the Study Drug	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 11 years

Determination of anti-obinutuzumab antibodies in serum samples were performed using a validated enzyme-linked Immunosorbent Assay (ELISA) method. Participants were considered to be ADA positive if they were ADA negative or have missing data at baseline but develop an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post baseline samples was at least ≥ 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 11 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 11 years

Outcome measures

Outcome data not reported

Adverse Events

Obinutuzumab

Serious events: 44 serious events

Other events: 107 other events

Deaths: 5 deaths

Placebo

Serious events: 24 serious events

Other events: 94 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 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