Trial Outcomes & Findings for BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis (NCT NCT01499355)

Last Updated: 2017-01-18

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

276 participants

Primary outcome timeframe

Week 52

Results posted on

2017-01-18

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Run-In Period: 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 mycophenolate mofetil (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.	Double-Blind Period: Placebo Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy of oral steroids (prednisone or equivalent) and MMF.	Double-Blind Period: BIIB023 3 mg/kg BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy of oral steroids (prednisone or equivalent) and MMF.	Double-Blind Period: BIIB023 20 mg/kg BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy of oral steroids (prednisone or equivalent) and MMF.
Run-In Period STARTED	276	0	0	0
Run-In Period COMPLETED	245	0	0	0
Run-In Period NOT COMPLETED	31	0	0	0
Double-Blind Period STARTED	0	63	63	62
Double-Blind Period COMPLETED	0	40	38	39
Double-Blind Period NOT COMPLETED	0	23	25	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Run-In Period: 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 mycophenolate mofetil (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.	Double-Blind Period: Placebo Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy of oral steroids (prednisone or equivalent) and MMF.	Double-Blind Period: BIIB023 3 mg/kg BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy of oral steroids (prednisone or equivalent) and MMF.	Double-Blind Period: BIIB023 20 mg/kg BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy of oral steroids (prednisone or equivalent) and MMF.
Run-In Period Study Termination	15	0	0	0
Run-In Period Other	3	0	0	0
Run-In Period Death	2	0	0	0
Run-In Period Investigator Decision	2	0	0	0
Run-In Period Consent Withdrawn	1	0	0	0
Run-In Period Adverse Event	8	0	0	0
Double-Blind Period Adverse Event	0	2	3	2
Double-Blind Period Study Termination	0	18	16	14
Double-Blind Period Other	0	1	2	2
Double-Blind Period Death	0	1	0	0
Double-Blind Period Investigator Decision	0	0	3	3
Double-Blind Period Consent Withdrawn	0	0	1	2
Double-Blind Period Lost to Follow-up	0	1	0	0

Baseline Characteristics

BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Enrolled Participants n=276 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.
Age, Continuous	32.3 years STANDARD_DEVIATION 10.11 • n=5 Participants
Gender Female	242 Participants n=5 Participants
Gender Male	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.)

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=49 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=48 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52	25 percentage of participants Interval 14.7 to 35.3	16 percentage of participants Interval 7.6 to 25.0	31 percentage of participants Interval 20.3 to 42.3

SECONDARY outcome

Timeframe: 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.)

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.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=49 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=48 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Percentage of Participants Who Achieve Complete Renal Response at Week 52	6 percentage of participants	8 percentage of participants	8 percentage of participants

SECONDARY outcome

Timeframe: 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.)

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.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=49 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=48 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 1-day duration	2 Participants	3 Participants	2 Participants
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 27-day duration	0 Participants	0 Participants	1 Participants
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 78-day duration	0 Participants	1 Participants	0 Participants
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 141-day duration	1 Participants	0 Participants	0 Participants
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52 169-day duration	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=8 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=15 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52	10.6 weeks Interval 2.0 to 41.0	5.2 weeks Interval 2.0 to 28.0	4.1 weeks Interval 2.0 to 37.0

SECONDARY outcome

Timeframe: 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.)

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=18 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=15 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
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 No participants in this arm had a uPCR \< 1.0 mg/mg at Week 52.	22 percentage of participants Interval 6.1 to 38.3	13 percentage of participants Interval 0.0 to 27.8

SECONDARY outcome

Timeframe: 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.)

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).

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=21 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=14 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52	38 percentage of participants Interval 17.6 to 57.4	5 percentage of participants Interval 0.0 to 12.4	21 percentage of participants Interval 3.4 to 39.5

SECONDARY outcome

Timeframe: Day 1 to Week 12

Population: All enrolled participants

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.

Outcome measures

Outcome measures
Measure	Placebo n=276 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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	—	—
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 outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=63 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=62 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Any event	48 participants	60 participants	53 participants
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Moderate or severe event	26 participants	32 participants	22 participants
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Severe event	4 participants	6 participants	5 participants
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	15 participants	11 participants
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Event related to MMF	21 participants	24 participants	22 participants
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Serious event	7 participants	11 participants	10 participants
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	3 participants	2 participants
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Serious event related to MMF	6 participants	4 participants	3 participants
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period Fatal event	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo IV infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=39 Participants BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=40 Participants BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
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	45.6 days Standard Deviation 75.42	52.1 days Standard Deviation 106.72

Adverse Events

Run-in Period

Serious events: 28 serious events

Other events: 134 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 33 other events

Deaths: 0 deaths

BIIB023 3 mg/kg

Serious events: 11 serious events

Other events: 46 other events

Deaths: 0 deaths

BIIB023 20 mg/kg

Serious events: 10 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Biogen Study Medical Director

Biogen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Run-in Period n=276 participants at risk 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.	Placebo n=63 participants at risk Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 3 mg/kg n=63 participants at risk BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	BIIB023 20 mg/kg n=62 participants at risk BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.
Blood and lymphatic system disorders Anaemia	2.5% 7/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	11.3% 7/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Blood and lymphatic system disorders Leukopenia	3.6% 10/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	11.1% 7/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	7.9% 5/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Blood and lymphatic system disorders Neutropenia	1.1% 3/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	7.9% 5/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	0.00% 0/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Gastrointestinal disorders Diarrhoea	11.2% 31/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	12.9% 8/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Gastrointestinal disorders Nausea	5.1% 14/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	7.9% 5/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
General disorders Oedema peripheral	2.9% 8/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Infections and infestations Bronchitis	3.6% 10/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	11.3% 7/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Infections and infestations Gastroenteritis	3.3% 9/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	11.3% 7/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Infections and infestations Influenza	1.4% 4/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.5% 4/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Infections and infestations Nasopharyngitis	4.7% 13/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	7.9% 5/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	8.1% 5/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Infections and infestations Upper respiratory tract infection	7.6% 21/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	11.1% 7/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	20.6% 13/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.7% 6/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Infections and infestations Urinary tract infection	2.9% 8/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	3.2% 2/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Metabolism and nutrition disorders Hypokalaemia	4.0% 11/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Musculoskeletal and connective tissue disorders Arthralgia	3.6% 10/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	8.1% 5/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Nervous system disorders Dizziness	1.1% 3/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Nervous system disorders Headache	4.3% 12/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.5% 6/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	11.1% 7/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.7% 6/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Renal and urinary disorders Proteinuria	0.36% 1/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	7.9% 5/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	9.7% 6/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Skin and subcutaneous tissue disorders Alopecia	2.9% 8/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	1.6% 1/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	7.9% 5/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	4.8% 3/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Skin and subcutaneous tissue disorders Rash	2.9% 8/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	0.00% 0/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.
Vascular disorders Hypertension	3.6% 10/276 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	0.00% 0/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	6.3% 4/63 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.	8.1% 5/62 • AEs: Run-in Day 1 through Week 64 +/- 5 days. SAEs: Screening through Week 64 +/- 5 days.