A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome

Overall RFS was defined as the time from randomization to first relapse or death. Relapse was defined as any of the following events: First-morning void UPCR ≥2 g/g; or dipstick UA ≥3+ for 3 consecutive days (home-monitoring) and the most recent urine sample determined to have UPCR >0.2 g/g as measured by the central laboratory; or dipstick UA protein ≥3+ on any single day with edema and urine sample determined to have UPCR > 0.2 g/g as measured by the central laboratory. Participants who withdrew their consent were censored at the time of withdrawal. Participants who were lost to follow-up were censored at the last assessment during scheduled or unscheduled visits. Kaplan-Meier (KM) estimates were used to evaluate the median RFS.

Cumulative corticosteroid dose was defined as the total dose received (mg/kg) of prednisone or equivalent, regardless of intercurrent events (relapse, rescue therapy, treatment discontinuation for any reason, and systemic corticosteroid usage for > 14 days) in participants prior to experiencing death. Topical, intraarticular, or inhaled corticosteroids and IV methylprednisolone given as a pre-medication were not included in this analysis.

Relapses were evaluated using adjusted rate ratio from baseline to Week 52, regardless of IEs (relapse, TDAR \& systemic corticosteroid usage for >14 days) in participants before receiving rescue therapy (RT)/experiencing death. Total number of relapses occurring during treatment period were evaluated by accounting for number of relapses experienced \& participant's follow-up time. Participant level relapse \& follow-up time data were aggregated, \& rate of relapses was compared between the two arms. Rate of relapse was analyzed using a negative binomial model with a log link \& log of each participant's follow up time as offset variable. Relapse=any of the following events: First-morning void UPCR ≥2 g/g; or dipstick UA ≥3+ for 3 consecutive days (home-monitoring) \& most recent urine sample determined to have UPCR >0.2 g/g as measured by the central laboratory; or dipstick UA protein ≥ 3+ on any single day with edema \& urine sample determined to have UPCR >0.2 g/g per central laboratory.

Sustained complete remission=first morning void UPCR ≤ 0.2 g/g at Week 76 without the occurrence of relapse or any other IE (except TDAR). Relapse=Any of the following events: First-morning void UPCR ≥ 2 g/g; or dipstick UA ≥3+ for 3 consecutive days (home-monitoring) \& the most recent urine sample determined to have UPCR > 0.2 g/g as measured by the central laboratory; or dipstick UA protein ≥ 3+ on any single day with edema \& urine sample determined to have UPCR > 0.2 g/g as measured by the central laboratory. Other IEs include: Any systemic corticosteroids usage for >14 days in a 30 day period; Initiation of any rescue therapy for INS, other than systemic corticosteroids; Death or TDAR. Participants with FRNS/SDNS who were randomized into the study at least 24 weeks prior to the date of randomization for the final participant in the study were only analyzed in this endpoint. Percentages have been rounded off.

Probability of RFS at Week 52 was defined as the percentage of participants remaining free of relapse or death at Week 52. Relapse was defined as any of the following events: First-morning void UPCR ≥2 g/g; or dipstick UA ≥3+ for 3 consecutive days (home-monitoring) and the most recent urine sample determined to have UPCR > 0.2 g/g as measured by the central laboratory; or dipstick UA protein ≥ 3+ on any single day with edema and urine sample determined to have UPCR > 0.2 g/g as measured by the central laboratory. Participants who withdrew their consent were censored at the time of withdrawal. Participants who were lost to follow-up were censored at the last assessment during scheduled or unscheduled visits. K-M method was used to estimate the RFS rate at Week 52. Percentages have been rounded off.

Edema-associated relapse definition is the same as the definition of relapse except that the edema-associated relapse definition additionally requires that participant edema is present and documented in the eCRF at the time of the relapse event. Relapse=any of the following events: First-morning void UPCR ≥ 2 g/g; or dipstick UA ≥3+ for 3 consecutive days (home-monitoring) \& the most recent urine sample determined to have UPCR > 0.2 g/g, measured by the central laboratory; or dipstick UA protein ≥ 3+ on any single day with edema \& urine sample determined to have UPCR > 0.2 g/g as measured by the central laboratory. Percentages have been rounded off.

Mean Change in CureGN Edema scale was defined as the mean change in total edema severity from baseline to Week 52, regardless of relapse, systemic corticosteroids usage for >14 days in a 30 day period, and treatment discontinuation due to any reason, in participants prior to receiving rescue therapy and assuming death has not occurred. The CureGN edema scale was used to assess the total edema severity. Participants were asked to report the location of edema they experienced over the last month from eight different body areas (whole body, face, hands, arms, abdomen, genitalia, legs, feet) and rate its severity on a 6-point Likert scale (0=absent to 5=worst imaginable), with total scores ranging from 0-40. Higher score indicated worst edema severity. Adjusted mean change in the CureGN edema scale scores from baseline to Week 52 has been reported.

Mean Change in "General Fatigue" domain of PedsQL-MFS total score was defined as the mean change in total score of the "General Fatigue" domain from baseline to Week 52, regardless of relapse, systemic corticosteroids usage for >14 days in a 30-day period, \& treatment discontinuation due to any reason, in participants prior to receiving rescue therapy \& assuming death did not occur. PedsQL MFS is an 18-item, self-reported measure designed to assess fatigue in participants with acute or chronic health conditions. This was a standard version with a 1-month recall period. The measure assessed three components of fatigue: General Fatigue (6 items), Sleep/Rest Fatigue (6 items), \& Cognitive Fatigue (6 items). General fatigue scores were based on a 5-point Likert response format, ranging from 0 (Never) to 4 (Almost Always) \& transformed to 0-100 total score. Higher score=less fatigue. Adjusted mean change in general fatigue domain scores from baseline to Week 52 has been reported.

Mean Change in PF domain of PedsQL = mean change in the PF score from baseline to Week 52, regardless of relapse, systemic corticosteroids usage for >14 days in a 30-day period, \& treatment discontinuation due to any reason, in participants prior to receiving rescue therapy \& assuming death did not occur. The PedsQL 4.0 Generic Core Scale is a 23 item measure used to assess health-related quality of life, over a recall of either one month (standard version) or 7 days (acute version). The 4 core domains include PF (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items). Items are rated on a 5-point Likert scale ranging from 0 (never a problem) to 4 (almost always a problem). Once completed, items are reverse scored \& linearly transformed to 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0, with higher scores=better health-related quality of life. Adjusted mean change in PF domain scores from baseline to Week 52 has been reported.

An AE was defined as any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. As pre-specified in the SAP, analysis excludes AEs reported following rescue treatment other than corticosteroids.

Samples were collected pre- and post-infusion at Weeks 0, 2, 24, and 26 and single samples were collected at Weeks 4, 12, 32, and 52. Data reported is averaged over the weeks specified in the time frame.

Samples were collected pre- and post-infusion at Weeks 0, 2, 24, and 26 and single samples were collected at Weeks 4, 12, 32, and 52. Data reported is averaged over the weeks specified in the time frame.

Samples were collected pre- and post-infusion at Weeks 0, 2, 24, and 26 and single samples were collected at Weeks 4, 12, 32, and 52. Data reported is averaged over the weeks specified in the time frame.