Lupus Nephritis
Conditions
Brief summary
The primary objective of the study is to assess the efficacy of BIIB023 as an add-on treatment to background therapy compared with placebo in combination with background therapy in the treatment of participants with active, biopsy-proven lupus nephritis. The secondary objectives of this study are to assess the safety and tolerability of BIIB023 compared with placebo in this study population.
Detailed description
Participants who complete this study through Week 52 will be offered the option to enter an Extension study under a separate protocol 211LE202 (NCT0193089).
Interventions
BIOLOGICALBIIB023
BIOLOGICALPlacebo
DRUGmycophenolate mofetil
titrated to a target daily dose of 2 g (1 g twice daily)
oral corticosteroids (prednisone or equivalent) at a target prednisone dose of 10 mg/day
Sponsors
Biogen
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
Key Inclusion Criteria: * Documented diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria. At least 4 ACR criteria must be documented, 1 of which must be a positive antinuclear antibody (ANA), anti Sm, or anti dsDNA antibody. * Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis with either active or active/chronic disease, confirmed by biopsy within 3 months prior to Screening. Participants are permitted to have co existing Class V lupus nephritis. If a renal biopsy has not been performed within 3 months of the Screening Visit, one can be performed during the Screening Period after all other eligibility criteria have been confirmed. The local histological diagnosis must be confirmed by the central study pathologist. * Must have proteinuria at Screening (from a 24 hour urine sample collection) defined as urinary protein:creatinine ratio (uPCR) \>1.0 mg/mg. Key
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 at Screening * Estimated glomerular filtration rate (eGFR) \<30 mL/min per 1.73 m\^2 (calculated using the abbreviated Modification of Diet in Renal Disease equation) or the presence of oliguria or end-stage renal disease requiring dialysis or transplantation * Subjects requiring dialysis within 12 months prior to Screening * History of renal transplant * Treatment with any biologic B-cell-depleting therapy (e.g., anti-CD20 \[rituximab\], anti-CD22 \[epratuzumab\], anti-BLyS/B-cell activating factor \[e.g., briobacept, belimumab\] therapy), or TACI-Ig within 12 months prior to Run-in Day 1. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52 | Week 52 | Complete renal response is defined as: (1) urinary protein:creatinine ratio (uPCR) \< 0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline; from a 24 hour urine collection); and (2) estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | Week 52 | Duration of response was calculated as the days in between the date of Week 52 visit and the date when the participant last became complete renal responder on or before Week 52 visit. Complete renal response: (1) uPCR \<0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. |
| Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52 | Baseline to Week 52 | Onset of renal response was calculated as weeks elapsed from baseline date to first visit where renal response was achieved. Complete renal response is defined as: (1) uPCR \<0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve. |
| Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52 | Baseline (Day 1), Week 52 | — |
| Percentage of Participants Who Achieve Complete Renal Response at Week 52 | Week 52 | Complete renal response is defined as uPCR \< 0.5 mg/mg with ≥ 50% reduction of uPCR from Baseline (from a 24-hour urine collection) and eGFR within normal range. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Day 1 to Week 12 | AEs that had an onset on or after dosing of MMF on run-in Day 1 up to the first double-blind dose, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. |
| Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Week 12 to Week 56 | AEs that had an onset on or after dosing of BIIB023 or placebo, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above. |
| Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study | up to Week 52 | Number of days between first visit with response to last consecutive visit with partial or complete response. Complete renal response is defined as: (1) uPCR \<0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve. |
| Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52 | Baseline, Week 52 | Active urinary sediment is defined by 1 of the following (in the absence of a urinary tract infection or menses): \> 5 red blood cell/high power field (RBC/HPF) or above the reference range for the laboratory, and \> 5 white blood cell/high power field (WBC/HPF) or above the reference range for the laboratory, and presence of cellular casts (RBC or WBC). Inactive urinary sediment is defined as: \< 5 RBC/HPF and \< 5 WBC/HPF, or within the laboratory reference range, and no cellular casts (no RBC or WBC casts). |
Countries
Argentina, Australia, Belgium, Brazil, Colombia, France, Germany, Hong Kong, Hungary, Italy, Malaysia, Mexico, Peru, Philippines, Poland, Portugal, Russia, South Korea, Spain, Thailand, United States
Participant flow
Pre-assignment details
A total of 276 participants were enrolled and 203 completed the run-in period and qualified for randomization; of these, 15 participants were not randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled Participants At Run-in Day 1, participants entering the study received oral corticosteroid (prednisone or equivalent) starting at 0.75 mg/kg/day (maximum allowed dose of 60 mg/day) for 2 weeks and subsequently tapered over an 8-week period to 10 mg/day by Run-in Week 10. Following confirmation of eligibility, subjects also received MMF starting at Run-in Day 1 at a total dose of 1 g/day and titrated to a target dose of 2 g/day by Run-in Week 2. | 276 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 0 | 2 | 3 | 2 |
| Double-Blind Period | Consent Withdrawn | 0 | 0 | 1 | 2 |
| Double-Blind Period | Death | 0 | 1 | 0 | 0 |
| Double-Blind Period | Investigator Decision | 0 | 0 | 3 | 3 |
| Double-Blind Period | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Double-Blind Period | Other | 0 | 1 | 2 | 2 |
| Double-Blind Period | Study Termination | 0 | 18 | 16 | 14 |
| Run-In Period | Adverse Event | 8 | 0 | 0 | 0 |
| Run-In Period | Consent Withdrawn | 1 | 0 | 0 | 0 |
| Run-In Period | Death | 2 | 0 | 0 | 0 |
| Run-In Period | Investigator Decision | 2 | 0 | 0 | 0 |
| Run-In Period | Other | 3 | 0 | 0 | 0 |
| Run-In Period | Study Termination | 15 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Enrolled Participants |
|---|---|
| Age, Continuous | 32.3 years STANDARD_DEVIATION 10.11 |
| Gender Female | 242 Participants |
| Gender Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 134 / 276 | 33 / 63 | 46 / 63 | 43 / 62 |
| serious Total, serious adverse events | 28 / 276 | 7 / 63 | 11 / 63 | 10 / 62 |
Outcome results
Primary
Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52
Complete renal response is defined as: (1) urinary protein:creatinine ratio (uPCR) \< 0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline; from a 24 hour urine collection); and (2) estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range).
Time frame: Week 52
Population: Participants in the modified intent-to-treat (mITT) population (participants in ITT population except for those who withdrew from study due to study early termination. Includes participants who completed Week 44 infusion and Visits at Week 52/Early Withdrawal and Week 56/End of Study but withdrew due to study early termination.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52 | 25 percentage of participants |
| BIIB023 3 mg/kg | Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52 | 16 percentage of participants |
| BIIB023 20 mg/kg | Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52 | 31 percentage of participants |
Secondary
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52
Duration of response was calculated as the days in between the date of Week 52 visit and the date when the participant last became complete renal responder on or before Week 52 visit. Complete renal response: (1) uPCR \<0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range.
Time frame: Week 52
Population: Participants in the mITT population (participants in ITT population except for those who withdrew from study due to study early termination. (Includes participants who completed Week 44 infusion and Visits at Week 52/Early Withdrawal and Week 56/End of Study but withdrew due to study early termination.)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 78-day duration | 0 Participants |
| Placebo | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 1-day duration | 2 Participants |
| Placebo | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 169-day duration | 0 Participants |
| Placebo | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 27-day duration | 0 Participants |
| Placebo | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 141-day duration | 1 Participants |
| BIIB023 3 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 27-day duration | 0 Participants |
| BIIB023 3 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 78-day duration | 1 Participants |
| BIIB023 3 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 141-day duration | 0 Participants |
| BIIB023 3 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 169-day duration | 0 Participants |
| BIIB023 3 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 1-day duration | 3 Participants |
| BIIB023 20 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 141-day duration | 0 Participants |
| BIIB023 20 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 27-day duration | 1 Participants |
| BIIB023 20 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 1-day duration | 2 Participants |
| BIIB023 20 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 78-day duration | 0 Participants |
| BIIB023 20 mg/kg | Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 | 169-day duration | 1 Participants |
Secondary
Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study
Number of days between first visit with response to last consecutive visit with partial or complete response. Complete renal response is defined as: (1) uPCR \<0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve.
Time frame: up to Week 52
Population: The ITT population included all participants who were randomized and received at least 1 dose of study treatment (BIIB023 or placebo).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study | 48.3 days | Standard Deviation 83.23 |
| BIIB023 3 mg/kg | Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study | 45.6 days | Standard Deviation 75.42 |
| BIIB023 20 mg/kg | Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study | 52.1 days | Standard Deviation 106.72 |
p-value: 0.863Regression, Cox
p-value: 0.769Regression, Cox
p-value: 0.907ANCOVA
p-value: 0.996ANCOVA
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period
AEs that had an onset on or after dosing of MMF on run-in Day 1 up to the first double-blind dose, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above.
Time frame: Day 1 to Week 12
Population: All enrolled participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Any Event | 209 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Moderate or Severe Event | 94 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Severe Event | 18 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Related Event to MMF | 90 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Serious Event | 28 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Related Serious Event to MMF | 12 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Fatal Event | 2 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Discontinued Treatment Due to Event | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period | Withdrew From Study Due to Event | 10 participants |
Secondary
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period
AEs that had an onset on or after dosing of BIIB023 or placebo, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above.
Time frame: Week 12 to Week 56
Population: The safety population was defined as all subjects who received at least 1 dose of study treatment (including placebo or BIIB023).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Event related to double-blind treatment | 5 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Fatal event | 1 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event | 7 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Event related to MMF | 21 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Any event | 48 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event related to MMF | 6 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Severe event | 4 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Moderate or severe event | 26 participants |
| Placebo | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event related to double-blind treatment | 3 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Event related to MMF | 24 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Any event | 60 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Moderate or severe event | 32 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Severe event | 6 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Event related to double-blind treatment | 15 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event | 11 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event related to double-blind treatment | 3 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event related to MMF | 4 participants |
| BIIB023 3 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Fatal event | 0 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Severe event | 5 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Any event | 53 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event related to double-blind treatment | 2 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Moderate or severe event | 22 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Fatal event | 0 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Event related to MMF | 22 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Event related to double-blind treatment | 11 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event related to MMF | 3 participants |
| BIIB023 20 mg/kg | Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period | Serious event | 10 participants |
Secondary
Percentage of Participants Who Achieve Complete Renal Response at Week 52
Complete renal response is defined as uPCR \< 0.5 mg/mg with ≥ 50% reduction of uPCR from Baseline (from a 24-hour urine collection) and eGFR within normal range.
Time frame: Week 52
Population: Participants in the mITT population (participants in ITT population except for those who withdrew from study due to study early termination. Includes participants who completed Week 44 infusion and Visits at Week 52/early withdrawal and Week 56/End of Study but withdrew due to study early termination.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieve Complete Renal Response at Week 52 | 6 percentage of participants |
| BIIB023 3 mg/kg | Percentage of Participants Who Achieve Complete Renal Response at Week 52 | 8 percentage of participants |
| BIIB023 20 mg/kg | Percentage of Participants Who Achieve Complete Renal Response at Week 52 | 8 percentage of participants |
Secondary
Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52
Active urinary sediment is defined by 1 of the following (in the absence of a urinary tract infection or menses): \> 5 red blood cell/high power field (RBC/HPF) or above the reference range for the laboratory, and \> 5 white blood cell/high power field (WBC/HPF) or above the reference range for the laboratory, and presence of cellular casts (RBC or WBC). Inactive urinary sediment is defined as: \< 5 RBC/HPF and \< 5 WBC/HPF, or within the laboratory reference range, and no cellular casts (no RBC or WBC casts).
Time frame: Baseline, Week 52
Population: Participants with active urinary sediment at Day 1 in the mITT population (participants in ITT population except for those who withdrew from study due to study early termination. (Includes participants who completed Week 44 infusion and Visits at Week 52/Early Withdrawal and Week 56/End of Study but withdrew due to study early termination.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52 | 38 percentage of participants |
| BIIB023 3 mg/kg | Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52 | 5 percentage of participants |
| BIIB023 20 mg/kg | Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52 | 21 percentage of participants |
p-value: 0.045690% CI: [0.0081, 0.4843]Regression, Logistic
p-value: 0.545590% CI: [0.0996, 1.8941]Regression, Logistic
p-value: 0.0252Cochran-Mantel-Haenszel
p-value: 0.2876Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52
Time frame: Baseline (Day 1), Week 52
Population: Participants with a uPCR \> 3.0 mg/mg at Baseline in the mITT population (participants in ITT population except for those who withdrew from study due to study early termination. Includes those who completed Week 44 infusion and Visits at Week 52/Early Withdrawal and Week 56/End of Study but withdrew due to study early termination.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52 | 0 percentage of participants |
| BIIB023 3 mg/kg | Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52 | 22 percentage of participants |
| BIIB023 20 mg/kg | Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52 | 13 percentage of participants |
p-value: 0.0486Cochran-Mantel-Haenszel
p-value: 0.0668Cochran-Mantel-Haenszel
Secondary
Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52
Onset of renal response was calculated as weeks elapsed from baseline date to first visit where renal response was achieved. Complete renal response is defined as: (1) uPCR \<0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of \< 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR \< 3.0 mg/mg if the Day 1 (Baseline) ratio was \> 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 \[Baseline\] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve.
Time frame: Baseline to Week 52
Population: Participants in the ITT population who achieved a renal response at Week 52. The ITT population included all participants who were randomized and received at least 1 dose of study treatment (BIIB023 or placebo).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52 | 10.6 weeks |
| BIIB023 3 mg/kg | Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52 | 5.2 weeks |
| BIIB023 20 mg/kg | Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52 | 4.1 weeks |
p-value: 0.367Cox proportional hazard
p-value: 0.283Cox proportional hazard