Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN) (NCT NCT02550652)

Last Updated: 2024-08-27

Results Overview

Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by \< 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio \< 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN range of central laboratory values.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

126 participants

Primary outcome timeframe

From baseline to Week 52

Results posted on

2024-08-27

Participant Flow

A total of 126 patients were enrolled in the study however one patient randomized to obinutuzumab did not receive study treatment due to a positive pregnancy test, but prior to the first study drug infusion; therefore a total of 125 patients are included in the analysis.

Participant milestones

Participant milestones
Measure	OBINUTUZUMAB 1000MG and MMF Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Overall Study STARTED	63	62
Overall Study COMPLETED	55	44
Overall Study NOT COMPLETED	8	18

Reasons for withdrawal

Reasons for withdrawal
Measure	OBINUTUZUMAB 1000MG and MMF Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Overall Study Death	1	4
Overall Study Lack of Efficacy	1	0
Overall Study Withdrawal by Subject	4	7
Overall Study Post Trial Access	1	0
Overall Study Lost to Follow-up	1	3
Overall Study Physician Decision	0	2
Overall Study Receipt of additional therapies that reduce peripheral B cell counts	0	2

Baseline Characteristics

The number analyzed indicates the number of participants with non-missing results at baseline. Values below the level of quantification have been excluded from the analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	Total n=125 Participants Total of all reporting groups
Age, Continuous	33.1 Years STANDARD_DEVIATION 9.8 • n=63 Participants	31.9 Years STANDARD_DEVIATION 10.1 • n=62 Participants	32.5 Years STANDARD_DEVIATION 9.9 • n=125 Participants
Sex: Female, Male Female	55 Participants n=63 Participants	51 Participants n=62 Participants	106 Participants n=125 Participants
Sex: Female, Male Male	8 Participants n=63 Participants	11 Participants n=62 Participants	19 Participants n=125 Participants
Race/Ethnicity, Customized Hispanic Or Latino	42 Participants n=63 Participants	49 Participants n=62 Participants	91 Participants n=125 Participants
Race/Ethnicity, Customized Not Hispanic Or Latino	20 Participants n=63 Participants	12 Participants n=62 Participants	32 Participants n=125 Participants
Race/Ethnicity, Customized Not Stated	1 Participants n=63 Participants	0 Participants n=62 Participants	1 Participants n=125 Participants
Race/Ethnicity, Customized Unknown	13 Participants n=63 Participants	12 Participants n=62 Participants	25 Participants n=125 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	11 Participants n=63 Participants	17 Participants n=62 Participants	28 Participants n=125 Participants
Race/Ethnicity, Customized Asian	3 Participants n=63 Participants	2 Participants n=62 Participants	5 Participants n=125 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=63 Participants	5 Participants n=62 Participants	11 Participants n=125 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=63 Participants	0 Participants n=62 Participants	1 Participants n=125 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islande	1 Participants n=63 Participants	0 Participants n=62 Participants	1 Participants n=125 Participants
Race/Ethnicity, Customized White	28 Participants n=63 Participants	26 Participants n=62 Participants	54 Participants n=125 Participants
Circulating CD19-Positive B-Cell Levels	328 cells/uL STANDARD_DEVIATION 331 • n=48 Participants • The number analyzed indicates the number of participants with non-missing results at baseline. Values below the level of quantification have been excluded from the analysis.	353 cells/uL STANDARD_DEVIATION 454 • n=48 Participants • The number analyzed indicates the number of participants with non-missing results at baseline. Values below the level of quantification have been excluded from the analysis.	341 cells/uL STANDARD_DEVIATION 395 • n=96 Participants • The number analyzed indicates the number of participants with non-missing results at baseline. Values below the level of quantification have been excluded from the analysis.
Region of Enrollment Asia	2 Participants n=62 Participants • The number analyzed represents the number of patients contributing to summary statistics.	2 Participants n=61 Participants • The number analyzed represents the number of patients contributing to summary statistics.	4 Participants n=123 Participants • The number analyzed represents the number of patients contributing to summary statistics.
Region of Enrollment European Union	16 Participants n=62 Participants • The number analyzed represents the number of patients contributing to summary statistics.	5 Participants n=61 Participants • The number analyzed represents the number of patients contributing to summary statistics.	21 Participants n=123 Participants • The number analyzed represents the number of patients contributing to summary statistics.
Region of Enrollment Latin America	37 Participants n=62 Participants • The number analyzed represents the number of patients contributing to summary statistics.	46 Participants n=61 Participants • The number analyzed represents the number of patients contributing to summary statistics.	83 Participants n=123 Participants • The number analyzed represents the number of patients contributing to summary statistics.
Region of Enrollment United States	7 Participants n=62 Participants • The number analyzed represents the number of patients contributing to summary statistics.	8 Participants n=61 Participants • The number analyzed represents the number of patients contributing to summary statistics.	15 Participants n=123 Participants • The number analyzed represents the number of patients contributing to summary statistics.
Lupus Nephritis (LN) Biopsy Class III	14 Participants n=63 Participants	17 Participants n=62 Participants	31 Participants n=125 Participants
Lupus Nephritis (LN) Biopsy Class IV	49 Participants n=63 Participants	45 Participants n=62 Participants	94 Participants n=125 Participants
Urine Protein Creatinine Ratio (UPCR)	3.32 mg/mg STANDARD_DEVIATION 2.66 • n=60 Participants • Due to a central lab error, uPCR was not available for the first 5 patients at baseline	2.93 mg/mg STANDARD_DEVIATION 2.46 • n=60 Participants • Due to a central lab error, uPCR was not available for the first 5 patients at baseline	3.12 mg/mg STANDARD_DEVIATION 2.56 • n=120 Participants • Due to a central lab error, uPCR was not available for the first 5 patients at baseline
Serum creatinine	0.87 (mg/dL) STANDARD_DEVIATION 0.34 • n=63 Participants	0.8 (mg/dL) STANDARD_DEVIATION 0.32 • n=62 Participants	0.84 (mg/dL) STANDARD_DEVIATION 0.34 • n=125 Participants

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Modified intent-to-treat population will include all randomized participants who have received any amount of study drug. Participants who received an incorrect therapy were reported under the treatment arm to which they were randomized.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52	22 Participants	14 Participants

SECONDARY outcome

Timeframe: From baseline to Week 52

OR includes both CRR and partial renal response (PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then urine protein:creatinine ratio of \<1.0. 2. If baseline protein:creatinine ratio is \> 3.0, then urine protein:creatinine ratio of \<3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or \<10 RBCs/HPF.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52	35 Participants	22 Participants

SECONDARY outcome

Timeframe: From baseline to Week 52

OR includes both CRR and partial renal response(PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in upcr, with one of these conditions met: 1. If baseline upcr is ≤3.0, then upcr of \<1.0. 2. If baseline pcr is \> 3.0, then upcr of \<3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or \<10 RBCs/HPF. Percentage of participants with response at various time points were measured using Kaplan Meier method.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Time to OR Over 52 Weeks Week 12	55 Participants	59 Participants
Time to OR Over 52 Weeks Week 24	33 Participants	37 Participants
Time to OR Over 52 Weeks Week 36	21 Participants	29 Participants
Time to OR Over 52 Weeks Week 52	14 Participants	21 Participants

SECONDARY outcome

Timeframe: Week 52

PRR defined as serum creatinine ≤15% above baseline value, no urinary red cell casts and either RBCs/HPF ≤ 50% above baseline or \< 10 RBCs/HPF, 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then a urine protein:creatinine ratio of \< 1.0. 2. If baseline protein:creatinine ratio is \> 3.0, then a urine protein:creatinine ratio of \< 3.0.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52	35 Participants	21 Participants

SECONDARY outcome

Timeframe: Week 24

CRR defined as normalization of serum creatinine, inactive urinary sediment (as evidenced by \< 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio \< 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined CRR at Week 24	16 Participants	17 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 52

CRR included normalization of serum creatinine, inactive urinary sediment (as evidenced by \< 10 RBCs/HPF and the absence of red cell casts) and urinary protein to creatinine ratio \< 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the ULN range of central laboratory values if baseline serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values. Percentage of participants with response at various time points were measured using Kaplan Meier method.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Time to CRR Over 52 Weeks Week 12	61 Participants	60 Participants
Time to CRR Over 52 Weeks Week 24	47 Participants	48 Participants
Time to CRR Over 52 Weeks Week 36	38 Participants	38 Participants
Time to CRR Over 52 Weeks Week 52	27 Participants	33 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Anti-dsDNA antibodies are a group of anti-nuclear autoantibodies targeting double stranded DNA.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52	-0.810 log IU/mL Standard Deviation 1.054	-0.076 log IU/mL Standard Deviation 1.103

SECONDARY outcome

Timeframe: Baseline and Week 52

Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Change From Baseline in Complement Component 3 (C3) Levels at Week 52	0.311 g/L Standard Deviation 0.302	0.106 g/L Standard Deviation 0.273

SECONDARY outcome

Timeframe: Baseline, Week 52

Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Change From Baseline in C4 Levels at Week 52	0.101 g/L Standard Deviation 0.117	0.004 g/L Standard Deviation 0.164

SECONDARY outcome

Timeframe: Week 52

mCRR1 has got two components only, i.e. serum Creatinine and urinary protein to creatinine ratio. mCRR1 is defined by attainment of normalization of serum creatinine as evidenced by 1.) serum creatinine ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine ≤ the ULN range of central laboratory values and 2.) Urinary protein to creatinine ratio \<0.5.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52	25 Participants	16 Participants

SECONDARY outcome

Timeframe: Week 52

mCRR2 is defined by normalization of serum creatinine, inactive urinary sediment (as evidenced by \< 10 RBCs/HPF and the absence of red cell casts), and urinary protein to creatinine ratio \<0.5. Normalization of serum creatinine as evidenced by the following: Serum creatinine ≤15% above baseline if baseline (Day 1) serum creatinine is above the normal range of the central laboratory values or ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52	28 Participants	21 Participants

SECONDARY outcome

Timeframe: Week 52

mCRR3 is defined by normalization of serum creatine as evidenced by serum creatinine ≤ the ULN range of central laboratory values and urinary protein to creatinine ratio \< 0.5.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52	29 Participants	24 Participants

SECONDARY outcome

Timeframe: From baseline to approximately 7 years and 8 months

Population: The safety population was defined as all participants who have received any amount of study medication. Participants are reported under the therapy they actually received.

An AE is 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 adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs), Infections and Serious infections. The AEs reported do not include events after the receipt of rescue medications.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=64 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=61 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants With Adverse Events (AEs) Adverse Events	58 Participants	54 Participants
Percentage of Participants With Adverse Events (AEs) Grade 3 AEs	19 Participants	15 Participants
Percentage of Participants With Adverse Events (AEs) Grade 4 AEs	6 Participants	7 Participants
Percentage of Participants With Adverse Events (AEs) Grade 5 AEs	1 Participants	2 Participants
Percentage of Participants With Adverse Events (AEs) Serious Adverse Events	16 Participants	17 Participants
Percentage of Participants With Adverse Events (AEs) Infections	48 Participants	38 Participants
Percentage of Participants With Adverse Events (AEs) Serious infections	5 Participants	10 Participants

SECONDARY outcome

Timeframe: From baseline to approximately 7 years and 8 months

Population: The safety population was defined as all participants who have received any amount of study medication. Participants are reported under the therapy they actually received.

Infusion related reaction is defined as any event reported within 24 hours of infusion and thought to be causally related to the investigational agent by the investigator. Grade 3 or higher infections include all events of Grade 3 to 5 under the SOC of infections and infestations. Drug-related neutropenia is defined as events in the Roche AE Grouped Term (AEGT) "Neutropenia and associated complications" and thought to be causally related to the investigational agent by the investigator. Drug-related thrombocytopenia is defined as events in the Standard MedDRA Query (SMQ) "Haematopoietic Thrombocytopenia narrow" and thought to be causally related to the investigational agent by the investigator.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=64 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=61 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia Infusion Related Reactions	10 Participants	6 Participants
Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia Grade 3 or Higher Infections	4 Participants	11 Participants
Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia Drug-related Neutropenia	3 Participants	2 Participants
Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia Drug-related Thrombocytopenia	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to approximately 7 years and 8 months

Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.

Antibodies are a blood protein produced in response to and counteracting a specific antigen.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab	7 Participants	—

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 12, Week 24, Week 52, Week 104, B Cell Follow-Up (Bcfu) at months 6, 12, 18, 24, 30, 36, 42 and 48

CD19+ B cell is a B-lymphocyte with a transmembrane protein that is encoded by the gene CD19.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Week 52	-98.620 Percent change of cells/uL Standard Deviation 5.677	37.695 Percent change of cells/uL Standard Deviation 220.857
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Week 2	-97.469 Percent change of cells/uL Standard Deviation 12.899	39.293 Percent change of cells/uL Standard Deviation 145.247
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Week 4	-98.777 Percent change of cells/uL Standard Deviation 5.235	-5.186 Percent change of cells/uL Standard Deviation 78.469
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Week 12	-97.045 Percent change of cells/uL Standard Deviation 15.506	0.661 Percent change of cells/uL Standard Deviation 134.421
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Week 24	-96.628 Percent change of cells/uL Standard Deviation 10.207	-11.446 Percent change of cells/uL Standard Deviation 86.793
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Week 104	77.123 Percent change of cells/uL Standard Deviation 380.111	-76.055 Percent change of cells/uL Standard Deviation 31.519
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 6	105.043 Percent change of cells/uL Standard Deviation 402.281	-73.889 Percent change of cells/uL Standard Deviation 19.755
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 12	77.123 Percent change of cells/uL Standard Deviation 380.111	-76.055 Percent change of cells/uL Standard Deviation 31.519
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 18	-83.159 Percent change of cells/uL Standard Deviation 16.701	-11.418 Percent change of cells/uL Standard Deviation NA The standard deviation could not be derived from the data of 1 participant.
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 24	-93.603 Percent change of cells/uL Standard Deviation 8.836	—
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 30	-59.950 Percent change of cells/uL Standard Deviation 50.807	—
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 36	-99.163 Percent change of cells/uL Standard Deviation 0.973	—
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 42	-99.084 Percent change of cells/uL Standard Deviation NA The standard deviation could not be derived from the data of 1 participant.	—
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels Bcfu Month 48	-99.851 Percent change of cells/uL Standard Deviation NA The standard deviation could not be derived from the data of 1 participant.	—

SECONDARY outcome

Timeframe: Week 0, Week 24, Week 52

Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab Week 0-24	559 ug/mL Standard Deviation 112	—
Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab Week 24-52	605 ug/mL Standard Deviation 115	—
Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab Week 0-52	605 ug/mL Standard Deviation 115	—

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab Week 0-24	10595 ug/mL*day Standard Deviation 4016	—
Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab Week 24-52	15811 ug/mL*day Standard Deviation 5543	—
Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab Week 0-52	26406 ug/mL*day Standard Deviation 9027	—

SECONDARY outcome

Timeframe: Day 0, Week 24, Week 52

Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Systemic Clearance of Obinutuzumab Day 0	0.255 L/day Standard Deviation 0.136	—
Systemic Clearance of Obinutuzumab Week 24	0.147 L/day Standard Deviation 0.0564	—
Systemic Clearance of Obinutuzumab Week 52	0.137 L/day Standard Deviation 0.0535	—

SECONDARY outcome

Timeframe: Day 0, Week 24, Week 52

Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Volume of Distribution Under Steady State (Vss) of Obinutuzumab Day 0	3.67 Litre (L) Standard Deviation 0.591	—
Volume of Distribution Under Steady State (Vss) of Obinutuzumab Week 24	3.67 Litre (L) Standard Deviation 0.591	—
Volume of Distribution Under Steady State (Vss) of Obinutuzumab Week 52	3.67 Litre (L) Standard Deviation 0.591	—

SECONDARY outcome

Timeframe: Day 0, Week 24, Week 52

Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=64 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Terminal Plasma Half-Life (t1/2) of Obinutuzumab Day 0	13.1 day Standard Deviation 3.7	—
Terminal Plasma Half-Life (t1/2) of Obinutuzumab Week 24	20.5 day Standard Deviation 5.6	—
Terminal Plasma Half-Life (t1/2) of Obinutuzumab Week 52	22.1 day Standard Deviation 6.7	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 12, 24, 36, 52

Each VAS had a range from 0-100 with higher scores indicating greater symptom impact on global health status.

Outcome measures

Outcome measures
Measure	OBINUTUZUMAB 1000MG and MMF n=63 Participants Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO and MMF n=62 Participants Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score Baseline	41.3 score on scale Standard Deviation 25.59	39.4 score on scale Standard Deviation 24.76
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score Week 4	-14.4 score on scale Standard Deviation 18.28	-8.7 score on scale Standard Deviation 22.69
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score Week 12	-19.9 score on scale Standard Deviation 25.07	-11.6 score on scale Standard Deviation 25.22
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score Week 24	-25.0 score on scale Standard Deviation 25.17	-20.8 score on scale Standard Deviation 24.74
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score Week 36	-24.8 score on scale Standard Deviation 25.71	-19.6 score on scale Standard Deviation 25.04
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score Week 52	-25.4 score on scale Standard Deviation 26.49	-23.3 score on scale Standard Deviation 25.76

Adverse Events

OBINUTUZUMAB 1000MG + MMF

Serious events: 17 serious events

Other events: 51 other events

Deaths: 1 deaths

PLACEBO + MMF

Serious events: 18 serious events

Other events: 39 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Genentech

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

Measure	OBINUTUZUMAB 1000MG + MMF n=64 participants at risk Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.	PLACEBO + MMF n=61 participants at risk Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Blood and lymphatic system disorders ANAEMIA	7.8% 5/64 • Number of events 5 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	6.6% 4/61 • Number of events 6 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Gastrointestinal disorders ABDOMINAL PAIN	7.8% 5/64 • Number of events 7 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	4.9% 3/61 • Number of events 3 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Gastrointestinal disorders DIARRHOEA	4.7% 3/64 • Number of events 3 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	8.2% 5/61 • Number of events 5 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Gastrointestinal disorders NAUSEA	9.4% 6/64 • Number of events 7 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	4.9% 3/61 • Number of events 3 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
General disorders CHEST PAIN	0.00% 0/64 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	6.6% 4/61 • Number of events 4 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations BRONCHITIS	20.3% 13/64 • Number of events 15 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	8.2% 5/61 • Number of events 8 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations CONJUNCTIVITIS	6.2% 4/64 • Number of events 6 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	3.3% 2/61 • Number of events 2 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations GASTROENTERITIS	4.7% 3/64 • Number of events 4 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	9.8% 6/61 • Number of events 9 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations HERPES ZOSTER	7.8% 5/64 • Number of events 6 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	9.8% 6/61 • Number of events 7 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations INFLUENZA	6.2% 4/64 • Number of events 4 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	3.3% 2/61 • Number of events 3 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations NASOPHARYNGITIS	7.8% 5/64 • Number of events 5 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	9.8% 6/61 • Number of events 8 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations PHARYNGITIS	7.8% 5/64 • Number of events 8 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	6.6% 4/61 • Number of events 4 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	9.4% 6/64 • Number of events 8 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	8.2% 5/61 • Number of events 6 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Infections and infestations URINARY TRACT INFECTION	21.9% 14/64 • Number of events 19 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	19.7% 12/61 • Number of events 20 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Injury, poisoning and procedural complications INFUSION RELATED REACTION	10.9% 7/64 • Number of events 7 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	9.8% 6/61 • Number of events 7 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Nervous system disorders HEADACHE	7.8% 5/64 • Number of events 7 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	4.9% 3/61 • Number of events 3 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Psychiatric disorders ANXIETY	0.00% 0/64 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	6.6% 4/61 • Number of events 4 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Vascular disorders HYPERTENSION	9.4% 6/64 • Number of events 6 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	3.3% 2/61 • Number of events 2 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Musculoskeletal and connective tissue disorders ARTHRALGIA	7.8% 5/64 • Number of events 6 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	6.6% 4/61 • Number of events 5 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.
Psychiatric disorders INSOMNIA	4.7% 3/64 • Number of events 3 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.	6.6% 4/61 • Number of events 4 • From baseline to approximately 7 years and 8 months The safety population was defined as all participants who have received any amount of study medication.