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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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).