Lupus Nephritis
Conditions
Brief summary
This Phase II study will compare the efficacy and safety of obinutuzumab plus mycophenolate mofetil (MMF)/mycophenolic acid (MPA) with placebo plus MMF/MPA in participants with proliferative LN.
Interventions
DRUGMycophenolate Mofetil/Mycophenolic Acid
MMF/MPA will be administered as per schedule specified in the respective arm.
DRUGObinutuzumab
Obinutuzumab will be administered as per schedule specified in the respective arm.
OTHERPlacebo
Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.
DRUGMethylprednisolone
Methylprednisolone IV will be administered as per schedule specified in the respective arm.
DRUGPrednisone
Prednisone will be administered as per schedule specified in the respective arm.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Systemic Lupus Erythematosus (SLE), according to current American College of Rheumatology (ACR) criteria * Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months prior to or during screening. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease * Proteinuria (urine protein to creatinine ratio) greater than (\>) 1.0 * For women who are not postmenopausal (greater than or equal to \[\>/=\] 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (\<) 1 percent (%) per year, during the treatment period and for at least 18 months after the last dose of study drug * For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 12 months after the last dose of study drug and agreement to refrain from donating sperm during this same period
Exclusion criteria
* Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE * Presence of rapidly progressive glomerulonephritis * Severe renal impairment as defined by estimated Glomerular Filtration Rate (GFR) \<30 milliliters per minute (mL/min) or the need for dialysis or renal transplant * Greater than 50% of glomeruli with sclerosis on renal biopsy * Treatment with cyclophosphamide or calcineurin inhibitors within the 3 months prior to randomization * Unstable disease with thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions * History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion * Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude participant participation * Concomitant chronic conditions, excluding SLE, (e.g., asthma, Crohn's disease) that required oral or systemic steroid use in the 52 weeks prior to screening * Previous treatment with an anti-cluster of differentiation (CD20)-targeted therapy within 12 months * Previous treatment with a biologic B-cell-targeted therapy (other than anti-CD20) within 6 months of randomization * Known intolerance to MMF or MPA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52 | From baseline to Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to OR Over 52 Weeks | 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. |
| Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52 | 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. |
| Percentage of Participants Who Achieve Protocol Defined CRR at Week 24 | 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. |
| Time to CRR Over 52 Weeks | 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. |
| Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52 | Baseline and Week 52 | Anti-dsDNA antibodies are a group of anti-nuclear autoantibodies targeting double stranded DNA. |
| Change From Baseline in Complement Component 3 (C3) Levels at Week 52 | Baseline and Week 52 | Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases. |
| Change From Baseline in C4 Levels at Week 52 | Baseline, Week 52 | Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases. |
| Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52 | 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. |
| Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52 | 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. |
| Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52 | 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. |
| Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52 | 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. |
| Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia | From baseline to approximately 7 years and 8 months | 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. |
| Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab | From baseline to approximately 7 years and 8 months | Antibodies are a blood protein produced in response to and counteracting a specific antigen. |
| Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | 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. |
| Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab | Week 0, Week 24, Week 52 | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab | Baseline to Week 52 | — |
| Systemic Clearance of Obinutuzumab | Day 0, Week 24, Week 52 | — |
| Volume of Distribution Under Steady State (Vss) of Obinutuzumab | Day 0, Week 24, Week 52 | — |
| Terminal Plasma Half-Life (t1/2) of Obinutuzumab | Day 0, Week 24, Week 52 | — |
| Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | 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. |
| Percentage of Participants With Adverse Events (AEs) | From baseline to approximately 7 years and 8 months | 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. |
Countries
Argentina, Brazil, Colombia, Costa Rica, France, Israel, Italy, Mexico, Panama, Peru, Spain, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 63 |
| 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. | 62 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 4 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Post Trial Access | 1 | 0 |
| Overall Study | Receipt of additional therapies that reduce peripheral B cell counts | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | OBINUTUZUMAB 1000MG and MMF | PLACEBO and MMF | Total |
|---|---|---|---|
| Age, Continuous | 33.1 Years STANDARD_DEVIATION 9.8 | 31.9 Years STANDARD_DEVIATION 10.1 | 32.5 Years STANDARD_DEVIATION 9.9 |
| Circulating CD19-Positive B-Cell Levels | 328 cells/uL STANDARD_DEVIATION 331 | 353 cells/uL STANDARD_DEVIATION 454 | 341 cells/uL STANDARD_DEVIATION 395 |
| Lupus Nephritis (LN) Biopsy Class III | 14 Participants | 17 Participants | 31 Participants |
| Lupus Nephritis (LN) Biopsy Class IV | 49 Participants | 45 Participants | 94 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 11 Participants | 17 Participants | 28 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Hispanic Or Latino | 42 Participants | 49 Participants | 91 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islande | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic Or Latino | 20 Participants | 12 Participants | 32 Participants |
| Race/Ethnicity, Customized Not Stated | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 26 Participants | 54 Participants |
| Region of Enrollment Asia | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment European Union | 16 Participants | 5 Participants | 21 Participants |
| Region of Enrollment Latin America | 37 Participants | 46 Participants | 83 Participants |
| Region of Enrollment United States | 7 Participants | 8 Participants | 15 Participants |
| Serum creatinine | 0.87 (mg/dL) STANDARD_DEVIATION 0.34 | 0.8 (mg/dL) STANDARD_DEVIATION 0.32 | 0.84 (mg/dL) STANDARD_DEVIATION 0.34 |
| Sex: Female, Male Female | 55 Participants | 51 Participants | 106 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 19 Participants |
| Urine Protein Creatinine Ratio (UPCR) | 3.32 mg/mg STANDARD_DEVIATION 2.66 | 2.93 mg/mg STANDARD_DEVIATION 2.46 | 3.12 mg/mg STANDARD_DEVIATION 2.56 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 64 | 4 / 61 |
| other Total, other adverse events | 51 / 64 | 39 / 61 |
| serious Total, serious adverse events | 17 / 64 | 18 / 61 |
Outcome results
Primary
Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52 | 22 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52 | 14 Participants |
p-value: 0.114595% CI: [-3.4, 28.1]Cochran-Mantel-Haenszel
p-value: 0.114580% CI: [2.1, 22.6]Cochran-Mantel-Haenszel
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab
Time frame: Baseline to Week 52
Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab | Week 0-24 | 10595 ug/mL*day | Standard Deviation 4016 |
| OBINUTUZUMAB 1000MG and MMF | Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab | Week 24-52 | 15811 ug/mL*day | Standard Deviation 5543 |
| OBINUTUZUMAB 1000MG and MMF | Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab | Week 0-52 | 26406 ug/mL*day | Standard Deviation 9027 |
Secondary
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52
Anti-dsDNA antibodies are a group of anti-nuclear autoantibodies targeting double stranded DNA.
Time frame: Baseline and 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | 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 |
| PLACEBO and MMF | Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52 | -0.076 log IU/mL | Standard Deviation 1.103 |
p-value: <0.000195% CI: [-1.13, -0.491]ANCOVA
p-value: <0.000180% CI: [-1.019, -0.602]ANCOVA
Secondary
Change From Baseline in C4 Levels at Week 52
Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
Time frame: Baseline, 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Change From Baseline in C4 Levels at Week 52 | 0.101 g/L | Standard Deviation 0.117 |
| PLACEBO and MMF | Change From Baseline in C4 Levels at Week 52 | 0.004 g/L | Standard Deviation 0.164 |
p-value: <0.000195% CI: [0.052, 0.124]ANCOVA
p-value: <0.000180% CI: [0.065, 0.112]ANCOVA
Secondary
Change From Baseline in Complement Component 3 (C3) Levels at Week 52
Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
Time frame: Baseline and 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Change From Baseline in Complement Component 3 (C3) Levels at Week 52 | 0.311 g/L | Standard Deviation 0.302 |
| PLACEBO and MMF | Change From Baseline in Complement Component 3 (C3) Levels at Week 52 | 0.106 g/L | Standard Deviation 0.273 |
p-value: 0.000495% CI: [0.081, 0.275]ANCOVA
p-value: 0.000480% CI: [0.115, 0.241]ANCOVA
Secondary
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score
Each VAS had a range from 0-100 with higher scores indicating greater symptom impact on global health status.
Time frame: Baseline (Day 1), Weeks 4, 12, 24, 36, 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| PLACEBO and MMF | Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | Week 52 | -23.3 score on scale | Standard Deviation 25.76 |
| PLACEBO and MMF | Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | Baseline | 39.4 score on scale | Standard Deviation 24.76 |
| PLACEBO and MMF | Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | Week 4 | -8.7 score on scale | Standard Deviation 22.69 |
| PLACEBO and MMF | Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | Week 12 | -11.6 score on scale | Standard Deviation 25.22 |
| PLACEBO and MMF | Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | Week 24 | -20.8 score on scale | Standard Deviation 24.74 |
| PLACEBO and MMF | Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score | Week 36 | -19.6 score on scale | Standard Deviation 25.04 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab
Time frame: Week 0, Week 24, Week 52
Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab | Week 0-24 | 559 ug/mL | Standard Deviation 112 |
| OBINUTUZUMAB 1000MG and MMF | Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab | Week 24-52 | 605 ug/mL | Standard Deviation 115 |
| OBINUTUZUMAB 1000MG and MMF | Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab | Week 0-52 | 605 ug/mL | Standard Deviation 115 |
Secondary
Percentage of Participants Who Achieve Protocol Defined CRR at 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.
Time frame: Week 24
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined CRR at Week 24 | 16 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined CRR at Week 24 | 17 Participants |
p-value: 0.846195% CI: [-17.5, 13.4]Cochran-Mantel-Haenszel
p-value: 0.846180% CI: [-12.1, 8.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at 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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52 | 25 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52 | 16 Participants |
p-value: 0.0995% CI: [-2.4, 30.1]Cochran-Mantel-Haenszel
p-value: 0.0980% CI: [3.2, 24.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at 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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52 | 35 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52 | 22 Participants |
p-value: 0.024695% CI: [3, 37.2]Cochran-Mantel-Haenszel
p-value: 0.024680% CI: [8.9, 31.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at 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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52 | 35 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52 | 21 Participants |
p-value: 0.01595% CI: [4.7, 38.7]Cochran-Mantel-Haenszel
p-value: 0.01580% CI: [10.6, 32.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at 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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52 | 28 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52 | 21 Participants |
p-value: 0.183895% CI: [-6.4, 27.6]Cochran-Mantel-Haenszel
p-value: 0.183880% CI: [-0.5, 21.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at 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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52 | 29 Participants |
| PLACEBO and MMF | Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52 | 24 Participants |
p-value: 0.372695% CI: [-10, 24.6]Cochran-Mantel-Haenszel
p-value: 0.372680% CI: [-4, 18.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Adverse Events (AEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Grade 4 AEs | 6 Participants |
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Serious Adverse Events | 16 Participants |
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Grade 3 AEs | 19 Participants |
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Infections | 48 Participants |
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Grade 5 AEs | 1 Participants |
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Serious infections | 5 Participants |
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Adverse Events (AEs) | Adverse Events | 58 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Serious infections | 10 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Adverse Events | 54 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Grade 3 AEs | 15 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Grade 4 AEs | 7 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Grade 5 AEs | 2 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Serious Adverse Events | 17 Participants |
| PLACEBO and MMF | Percentage of Participants With Adverse Events (AEs) | Infections | 38 Participants |
Secondary
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 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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| PLACEBO and MMF | 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 |
| PLACEBO and MMF | 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 | 6 Participants |
| PLACEBO and MMF | 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 | 2 Participants |
| PLACEBO and MMF | 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 | 11 Participants |
Secondary
Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab
Antibodies are a blood protein produced in response to and counteracting a specific antigen.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab | 7 Participants |
Secondary
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels
CD19+ B cell is a B-lymphocyte with a transmembrane protein that is encoded by the gene CD19.
Time frame: 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
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 2 | -97.469 Percent change of cells/uL | Standard Deviation 12.899 |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 104 | 77.123 Percent change of cells/uL | Standard Deviation 380.111 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | 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 |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Bcfu Month 42 | -99.084 Percent change of cells/uL | — |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Bcfu Month 48 | -99.851 Percent change of cells/uL | — |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 4 | -98.777 Percent change of cells/uL | Standard Deviation 5.235 |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 12 | -97.045 Percent change of cells/uL | Standard Deviation 15.506 |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 24 | -96.628 Percent change of cells/uL | Standard Deviation 10.207 |
| OBINUTUZUMAB 1000MG and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 52 | -98.620 Percent change of cells/uL | Standard Deviation 5.677 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 2 | 39.293 Percent change of cells/uL | Standard Deviation 145.247 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Bcfu Month 18 | -11.418 Percent change of cells/uL | — |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 4 | -5.186 Percent change of cells/uL | Standard Deviation 78.469 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 104 | -76.055 Percent change of cells/uL | Standard Deviation 31.519 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 12 | 0.661 Percent change of cells/uL | Standard Deviation 134.421 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Bcfu Month 12 | -76.055 Percent change of cells/uL | Standard Deviation 31.519 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 24 | -11.446 Percent change of cells/uL | Standard Deviation 86.793 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Bcfu Month 6 | -73.889 Percent change of cells/uL | Standard Deviation 19.755 |
| PLACEBO and MMF | Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels | Week 52 | 37.695 Percent change of cells/uL | Standard Deviation 220.857 |
Secondary
Systemic Clearance of Obinutuzumab
Time frame: Day 0, Week 24, Week 52
Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Systemic Clearance of Obinutuzumab | Day 0 | 0.255 L/day | Standard Deviation 0.136 |
| OBINUTUZUMAB 1000MG and MMF | Systemic Clearance of Obinutuzumab | Week 24 | 0.147 L/day | Standard Deviation 0.0564 |
| OBINUTUZUMAB 1000MG and MMF | Systemic Clearance of Obinutuzumab | Week 52 | 0.137 L/day | Standard Deviation 0.0535 |
Secondary
Terminal Plasma Half-Life (t1/2) of Obinutuzumab
Time frame: Day 0, Week 24, Week 52
Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Terminal Plasma Half-Life (t1/2) of Obinutuzumab | Day 0 | 13.1 day | Standard Deviation 3.7 |
| OBINUTUZUMAB 1000MG and MMF | Terminal Plasma Half-Life (t1/2) of Obinutuzumab | Week 24 | 20.5 day | Standard Deviation 5.6 |
| OBINUTUZUMAB 1000MG and MMF | Terminal Plasma Half-Life (t1/2) of Obinutuzumab | Week 52 | 22.1 day | Standard Deviation 6.7 |
Secondary
Time to CRR Over 52 Weeks
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Time to CRR Over 52 Weeks | Week 12 | 61 Participants |
| OBINUTUZUMAB 1000MG and MMF | Time to CRR Over 52 Weeks | Week 24 | 47 Participants |
| OBINUTUZUMAB 1000MG and MMF | Time to CRR Over 52 Weeks | Week 36 | 38 Participants |
| OBINUTUZUMAB 1000MG and MMF | Time to CRR Over 52 Weeks | Week 52 | 27 Participants |
| PLACEBO and MMF | Time to CRR Over 52 Weeks | Week 52 | 33 Participants |
| PLACEBO and MMF | Time to CRR Over 52 Weeks | Week 12 | 60 Participants |
| PLACEBO and MMF | Time to CRR Over 52 Weeks | Week 36 | 38 Participants |
| PLACEBO and MMF | Time to CRR Over 52 Weeks | Week 24 | 48 Participants |
p-value: 0.353Log Rank
Secondary
Time to OR Over 52 Weeks
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Time to OR Over 52 Weeks | Week 12 | 55 Participants |
| OBINUTUZUMAB 1000MG and MMF | Time to OR Over 52 Weeks | Week 24 | 33 Participants |
| OBINUTUZUMAB 1000MG and MMF | Time to OR Over 52 Weeks | Week 52 | 14 Participants |
| OBINUTUZUMAB 1000MG and MMF | Time to OR Over 52 Weeks | Week 36 | 21 Participants |
| PLACEBO and MMF | Time to OR Over 52 Weeks | Week 52 | 21 Participants |
| PLACEBO and MMF | Time to OR Over 52 Weeks | Week 24 | 37 Participants |
| PLACEBO and MMF | Time to OR Over 52 Weeks | Week 36 | 29 Participants |
| PLACEBO and MMF | Time to OR Over 52 Weeks | Week 12 | 59 Participants |
p-value: 0.0744Log Rank
Secondary
Volume of Distribution Under Steady State (Vss) of Obinutuzumab
Time frame: Day 0, Week 24, Week 52
Population: Pharmacokinetic population included all patients randomized to and received any dose of obinutuzumab given as study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OBINUTUZUMAB 1000MG and MMF | Volume of Distribution Under Steady State (Vss) of Obinutuzumab | Day 0 | 3.67 Litre (L) | Standard Deviation 0.591 |
| OBINUTUZUMAB 1000MG and MMF | Volume of Distribution Under Steady State (Vss) of Obinutuzumab | Week 24 | 3.67 Litre (L) | Standard Deviation 0.591 |
| OBINUTUZUMAB 1000MG and MMF | Volume of Distribution Under Steady State (Vss) of Obinutuzumab | Week 52 | 3.67 Litre (L) | Standard Deviation 0.591 |