Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

Phase 3

Terminated

Conditions: Lupus Nephritis

Interventions: Biological: BMS-188667
Drug: Mycophenolate mofetil
Biological: Placebo matching with BMS-188667
Drug: Prednisone

Registration Number: NCT01714817

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this study is to evaluate (Abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 695

Inclusion Criteria

Potential subjects must have active lupus nephritis
Biopsy within 12 months prior to screening visit indicating active Class 3 or 4 proliferative lupus glomerulonephritis (lupus effecting your kidney)
Urine protein creatinine ratio (UPCR) ≥ 1 at Screening
Serum creatinine ≤ 3 mg/dL (ie, ≤ 265 micromol/L)
There must also be evidence of active disease within 3 months of Screening, based on at least one of the following:
- Worsening of lupus nephritis OR
- UPCR ≥ 3 at Screening OR
- Active urine sediment OR
- Biopsy within 3 months prior to screening visit indicating active Class 3 or Class 4 active proliferative lupus glomerulonephritis

Inclusion Criteria for the Long-Term Extension Period:

Signed Written Informed Consent
Subjects who achieve a complete or partial renal response after completing 2 years of double-blind treatment

Exclusion Criteria

Systemic Lupus Erythematosus (SLE) must be the primary/main autoimmune diagnosis
Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study
Significant active Central nervous system (CNS) lupus with the exception of fatigue or mild stable cognitive
Subjects who are diagnosed as end-stage renal disease or whose kidney damage is too significant and irreversible

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BMS-188667 + Mycophenolate mofetil + Prednisone	BMS-188667	BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
Placebo + Mycophenolate mofetil + Prednisone	Placebo matching with BMS-188667	Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks
BMS-188667 + Mycophenolate mofetil + Prednisone	Mycophenolate mofetil	BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
BMS-188667 + Mycophenolate mofetil + Prednisone	Prednisone	BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
Placebo + Mycophenolate mofetil + Prednisone	Prednisone	Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks
Placebo + Mycophenolate mofetil + Prednisone	Mycophenolate mofetil	Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period	Day 365	Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. CR defined as: eGFR is normal or no \<85% of the baseline; eGFR based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equiv. for at least 28 days prior to assessment. Participants with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as having achieved CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use (Yes/No), race (Asian/ Black/Caucasian/Other) and baseline UPCR as a continuous variable.

Secondary Outcome Measures

Name	Time	Method
Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period	Day 365	Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.
Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants	Baseline and Day 365	Adjusted Mean Change from Baseline in UPCR at Day 365 of the double-blind period in nephrotic participants
Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population	Day 1 and Day 365	Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population
Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period	Day 1 to Day 365	Adjusted mean change from baseline in British Isles Lupus Assessment Group (BILAG) score over time during Year 1 of the double-blind period based on a repeated measure mixed model and presented at each visit in the first 12-month of the double-blind period. BILAG index measures disease activity in different organs/systems separately. BILAG score is calculated for each of 9 systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. BILAG "A" represents the presence of serious features of lupus. BILAG "B" represents more moderate features of the disease. BILAG "C" includes only mild symptomatic features. BILAG "D" represents prior activity with no current symptoms due to active lupus. BILAG "E" represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.
Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period	From Day 1 up to 56 days post last dose in Year 1 of the double-blind period	All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug.
Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period	Day 365, Day 729	Complete Renal Response or Complete Response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; UPCR \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment. Partial Renal Response or Partial Response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was greater than or equal to 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment. No Renal Response or No Response (NR): defined as not meeting criteria for CR or PR or withdrawn
Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants	Day 365, Day 729	The estimate of median time to Complete Renal Response in nephrotic participants is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment.
Median Time to Partial Renal Response During the Double-blind Period in All Participants	Day 365, Day 729	The estimate of median time to Partial Response (PR) is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment
Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period	Day 1 to Day 729	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA \<0.8X LLN OR \>1.2X ULN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.25X PRE RX OR \<LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.67X PRE RX OR \>ULN GLUCOSE, SERUM mmol/L 4.1 GLUC \<65 mg/dL, OR \>220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE 0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE 1.1X PRE RX OR \<LLN ALBUMIN g/L 3.0 ALB \<0.9X LLN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL \>2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period	Day 365, Day 729	Participants who experienced a positive antibody response relative to baseline (ECL Assay)
Median Time to Complete Renal Response During the Double-blind Period in All Participants	Day 365, Day 729	The estimate of median time to Complete Renal Response is based on Kaplan-Meier analysis. Complete renal response (CR): defined as meeting ALL of the following criteria: eGFR normal OR no less than 85% of the baseline value; Urine protein/creatinine ratio (UPCR) \< 0.5; Urine sediment: No cellular casts; Daily corticosteroid dose must be no greater than 10 mg prednisone or equivalent for at least 28 days prior to assessment.
Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants	Day 365, Day 729	The estimate of median time to Partial Response (PR) in nephrotic participants is based on Kaplan-Meier analysis. Partial renal response (PR): defined as meeting ALL of the following criteria: Participant does not meet criteria for CR; eGFR no less than 85% of the lesser of the values at screening or randomization (Day 1); UPCR \< 0.5 OR 50% reduced from baseline and \< 1 if baseline value was \< 3, OR 50% reduced from baseline and \< 3 if baseline value was 3; Urine sediment: no cellular casts; daily corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent for at least 28 days prior to assessment
Adjusted Mean Change From Baseline in UPCR Over Time	Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended	A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used.
Median Percent Change From Baseline in UPCR Over Time	Day 365, Day 729	A repeated measure mixed model that included the baseline UPCR value, randomization stratification factors, time, and time by treatment interaction as fixed effects and subject as a random effect was used. % Change from Baseline = (post baseline - baseline value) / baseline value x 100
Adjusted Mean Change From Baseline in eGFR Over Time	Day 365, Day 729	Estimated glomerular filtration rate(eGFR), will be calculated by the CKD-EPI formula shown below.50 eGFR is expressed as mL/min per 1.73m2. For the purpose of this study lower limit of normal eGFR is defined as 90mL/min per 1.73m2 eGFR = 141 X min (Scr/k, 1)α X max (Scr/k, 1)-1.209 X 0.993Age X (1.018 \[if female\]) X (1.159 \[if black\]) Where Scr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1, age in years.
Median Time to First Sustained Change to No Response During the Double-blind Period	Day 365, Day 729	Sustained response defined as response present at 2 consecutive visits approximately 4 weeks apart. No renal response (NR): defined as not meeting criteria for CR or PR or withdrawn The estimate of median time is based on Kaplan-Meier analysis
Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period	Day 365, Day 729	Sustained change to no response is defined as going from CR (or PR) to NR and remaining in NR for at least 2 consecutive visits; visits should be approximately 4 weeks apart. This analysis will be based on time from response CR (or PR) to the first visit in which the no response (NR) was achieved and sustained to the next visit.
Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period	Day 1 to Day 729; Day 365 to Day 729	BILAG index measures and reports disease activity in different organs/systems separately. The BILAG score is calculated for each of nine systems depending on the clinical features present and whether they are new (4 points), worse (3 points), the same (2 points), improving (1 point) or not present (0 points) in the last 4 weeks compared with previously. A BILAG "A" represents the presence of one or more serious features of lupus. A BILAG "B" represents more moderate features of the disease. A BILAG "C" includes only mild symptomatic features. A BILAG "D" represents only prior activity with no current symptoms due to active lupus. A BILAG "E" represents an organ that has never been involved. Overall BILAG score ranges from 0-108, with higher scores reflecting a worse outcome.
Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion	Days 1 to 365	Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365
Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV	at 1 hour post Day 1 dose and 30 minutes post Day 337 dose	Cmax: Maximum observed serum concentration following participants receiving active abatacept IV
AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval	Days 337 to 365	AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365.
Summary Statistics for Systolic Blood Pressure	Day 1 to Day 729	Summary statistics for systolic blood pressure
Summary Statistics for Diastolic Blood Pressure	Day 1 to Day 729	Summary statistics for diastolic blood pressure
Summary Statistics for Heart Rate	Day 1 to Day 729	Summary statistics for Heart Rate
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L)	Day 729	Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L)	Day 729	Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood)	Day 729	Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L)	Day 729	Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L)	Day 729	Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L)	Day 729	Laboratory assessments were analyzed centrally, with the exception of pregnancy testing. Blood draws and urine collections were performed at visits specified in the protocol. Change from Baseline = Post-baseline - Baseline value.
Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period	Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB \>3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT \<0.75X PRE RX ERYTHROCYTES x10\12 c/L 5.2 RBC \<0.75X PRE RX PLATELET COUNT x10\9 c/L 5.0 PLAT \<0.67X LLN OR \>1.5X ULN, OR IF PRE RX\<LLN THEN USE 0.5X PRE RX AND \<100,000/MM3 LEUKOCYTES x10\9 c/L 6.2 WBC \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.8X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.2X PRE RX OR \<LLN EOSINOPHILS (ABSOLUTE) x10\9 c/L 8.3 EOSA IF VALUE \> .750 X10\3 c/uL BASOPHILS (ABSOLUTE) x10\9 c/L 8.3 BASOA IF VALUE \> 400/MM3 MONOCYTES (ABSOLUTE) x10\9 c/L 8.3 MONOA IF VALUE \> 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10\9 c/L 8.3 LYMPA IF VALUE \< .750 X10\3 c/uL OR IF VALUE \> 7.50 X10\3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period	Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI \>2X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI \>1.5X ULN, OR IF PRE RX\>ULN THEN USE \>2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN \>2X PRE RX CREATININE umol/L 5.0 CREAT \>1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period	Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA \<0.95X LLN OR \>1.05X ULN, OR IF PRE RX\<LLN THEN USE \<0.95X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.05X PRE RX OR \<LLN POTASSIUM, SERUM mmol/L 4.1 K \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN CHLORIDE, SERUM mmol/L 5.0 CL \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period	Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4
Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period	Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value CALCIUM, TOTAL mmol/L 5.2 CA \<0.8X LLN OR \>1.2X ULN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.25X PRE RX OR \<LLN PHOSPHORUS, INORGANIC mmol/L 5.2 PHOS \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.67X PRE RX OR \>ULN GLUCOSE, SERUM mmol/L 4.1 GLUC \<65 mg/dL, OR \>220 mg/dL PROTEIN, TOTAL g/L 5.0 TPRO \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE 0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE 1.1X PRE RX OR \<LLN ALBUMIN g/L 3.0 ALB \<0.9X LLN, OR IF PRE RX\<LLN THEN USE \<0.75X PRE RX CHOLESTEROL, TOTAL (TC) mmol/L 5.2 CHOL \>2X PRE R N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension	From the first dose in Year 2 of the double-blind period up to 56 days post last dose	All AEs were coded and grouped into preferred terms (PT) by system organ class (SOC), using the Medical Dictionary for Regulatory Activities (MedDRA, version 21.0). Investigators determined the intensity of each AE as mild, moderate, severe, or very severe and assessed the relationship to study drug.
Percentage of Participants in Treatment Failure Over Time During the Double-blind Period	Day 365, Day 729	Lupus treatment failure is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor.
Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period	Day 365, Day 729	First treatment failure (or Lupus treatment failure) is defined as any of the following: Death, unless due to physical trauma or violence; Renal Flare; sustained doubling of creatinine from baseline (greater of Screening or Study Day 1 value); initiation of rescue therapy for treatment of active lupus nephritis after Study Week 20. Overall treatment failure is defined as lupus treatment failure plus discontinuation of study drug for any reason except death due to physical trauma or violence, pregnancy or administrative decision by Sponsor. The hazard ratio is estimated using the Cox proportional hazards model which includes treatment group, stratification variables (baseline ACEis/ARBs use, RACE) and baseline UPCR. The estimate of median time is based on Kaplan-Meier analysis
Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period	Day 729	Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.
Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period	Day 1 to Day 729	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value ALKALINE PHOSPHATASE (ALP) U/L 5.0 ALP \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX ASPARTATE AMINOTRANSFERASE (AST) U/L 5.0 AST \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX ALANINE AMINOTRANSFERASE (ALT) U/L 5.0 ALT \>3X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX G-GLUTAMYL TRANSFERASE (GGT) U/L 5.0 GGT \>2X ULN, OR IF PRE RX\>ULN THEN USE \>3X PRE RX BILIRUBIN, TOTAL umol/L 5.1 TBILI \>2X ULN, OR IF PRE RX\>ULN THEN USE \>4X PRE RX BILIRUBIN, DIRECT umol/L 5.1 DBILI \>1.5X ULN, OR IF PRE RX\>ULN THEN USE \>2X PRE RX BLOOD UREA NITROGEN mmol/L 5.1 BUN \>2X PRE RX CREATININE umol/L 5.0 CREAT \>1.5X PRE RX N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period	Day 1 to Day 729	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value SODIUM, SERUM mmol/L 4.0 NA \<0.95X LLN OR \>1.05X ULN, OR IF PRE RX\<LLN THEN USE \<0.95X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.05X PRE RX OR \<LLN POTASSIUM, SERUM mmol/L 4.1 K \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN CHLORIDE, SERUM mmol/L 5.0 CL \<0.9X LLN OR \>1.1X ULN, OR IF PRE RX\<LLN THEN USE \<0.9X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.1X PRE RX OR \<LLN N = the number of participants with at least 1 on treatment lab result for each analyte
Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period	Day 1 to Day 729	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value PROTEIN, URINE Unknown UPRO IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 GLUCOSE, URINE N/A UGLU IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 BLOOD, URINE N/A UBLD IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 RBC, URINE hpf 5.0 URBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4 WBC, URINE hpf 5.0 UWBC IF MISSING PRE THEN USE \>=2, OR IF VALUE \>=4, OR IF PRE RX =0 OR 0.5 THEN USE \>=2, OR IF PRE RX =1 THEN USE \>=3, OR IF PRE RX =2 OR 3 THEN USE \>=4
Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period	Day 729	Number of participants achieving CR was divided by total participants in that arm, expressed as a percentage. CR is defined the following criteria: eGFR is normal or no \<85% of the baseline value; eGFR is based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equivalent for at least 28 days prior. Subjects with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use, race and baseline UPCR as a continuous variable.
Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period	Day 1 to Day 729	LLN= Lower limit of normals ULN= Upper limit of normals Pre RX = Baseline value HEMOGLOBIN g/L 4.0 HB \>3 G/DL DECREASE FROM PRE RX HEMATOCRIT vol 6.3 HCT \<0.75X PRE RX ERYTHROCYTES x10\12 c/L 5.2 RBC \<0.75X PRE RX PLATELET COUNT x10\9 c/L 5.0 PLAT \<0.67X LLN OR \>1.5X ULN, OR IF PRE RX\<LLN THEN USE 0.5X PRE RX AND \<100,000/MM3 LEUKOCYTES x10\9 c/L 6.2 WBC \<0.75X LLN OR \>1.25X ULN, OR IF PRE RX\<LLN THEN USE \<0.8X PRE RX OR \>ULN, OR IF PRE RX\>ULN THEN USE \>1.2X PRE RX OR \<LLN EOSINOPHILS (ABSOLUTE) x10\9 c/L 8.3 EOSA IF VALUE \> .750 X10\3 c/uL BASOPHILS (ABSOLUTE) x10\9 c/L 8.3 BASOA IF VALUE \> 400/MM3 MONOCYTES (ABSOLUTE) x10\9 c/L 8.3 MONOA IF VALUE \> 2000/MM3 LYMPHOCYTES (ABSOLUTE) x10\9 c/L 8.3 LYMPA IF VALUE \< .750 X10\3 c/uL OR IF VALUE \> 7.50 X10\3 c/uL N = the number of participants with at least 1 on treatment lab result for each analyte

Trial Locations

Locations (42): Riesgo De Fractura S.A. Cayre Ips
🇨🇴
Bogota, Cundinamarca, Colombia
Circaribe S.A.S
🇨🇴
Barranquilla, Colombia
Servimed E.U
🇨🇴
Bucaramanga, Santander, Colombia
Hospital Universitario San Ignacio
🇨🇴
Bogota, Colombia
Emory University.
🇺🇸
Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Brigham & Women'S Hospital
🇺🇸
Boston, Massachusetts, United States
Boston University Medical Center
🇺🇸
Boston, Massachusetts, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
University Of Alabama At Birmingham (Uab)
🇺🇸
Birmingham, Alabama, United States
University Of Utah Hospital
🇺🇸
Salt Lake City, Utah, United States
University Of Connecticut Health Center
🇺🇸
Farmington, Connecticut, United States
Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
🇺🇸
Long Beach, California, United States
East Bay Rheumatology Medical Group, Inc.
🇺🇸
San Leandro, California, United States
Suny Downstate Medical Center
🇺🇸
Brooklyn, New York, United States
Northshore Lij Health System
🇺🇸
Great Neck, New York, United States
Paramount Medical Research & Consulting, Llc
🇺🇸
Middleburg Heights, Ohio, United States
Centro De Est D Inv. Basica Y Clinica
🇲🇽
Guadalajara, Jalisco, Mexico
Hospital Privado-Centro Medico De Cordoba S.A.
🇦🇷
Cordoba, Argentina
Shanahan Rheum & Immunotherapy, PLLC
🇺🇸
Raleigh, North Carolina, United States
Rheumatology Consultants Pllc
🇺🇸
Knoxville, Tennessee, United States
Organizacion Medica De Investigacion S.A. (Omi)
🇦🇷
Capital Federal, Buenos Aires, Argentina
Tulane University School Of Medicine
🇺🇸
New Orleans, Louisiana, United States
Integral Rheumatology & Immunology Specialists
🇺🇸
Plantation, Florida, United States
University Of Miami Miller School Of Medicine
🇺🇸
Miami, Florida, United States
Ochsner Clinic Foundation
🇺🇸
Baton Rouge, Louisiana, United States
Local Institution
🇹🇷
Edirne, Turkey
The Feinstein Institute For Medical Research
🇺🇸
Manhasset, New York, United States
Hospital For Special Surgery
🇺🇸
New York, New York, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Clinica De La Costa
🇨🇴
Barranquilla, Colombia
Hospital De Jesus
🇲🇽
Mexico City, Distrito Federal, Mexico
Hospital Pablo Tobon Uribe
🇨🇴
Medellin, Colombia
Hospital General De Mexico O.D.
🇲🇽
Mexico City, Distrito Federal, Mexico
Centro Potosino de Inv Clinica
🇲🇽
San Luis Potosi, Mexico
Hospital Nacional Guillermo Almenara Irigoyen
🇵🇪
Lima, Peru
Hosp Central I.Morones Prieto
🇲🇽
San Luis Potosi, Mexico
Hospital Nacional Cayetano Heredia
🇵🇪
Lima, Peru
Centro Medico De Las Americas
🇲🇽
Merida, Yucatan, Mexico
Instituto Nacional De Ciencias Medicas Y Nutricion S.Z.
🇲🇽
Distrito Federal, Mexico
Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac
🇵🇪
Lima, Peru
University Of North Carolina At Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States