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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01714817
Other study ID # IM101-291
Secondary ID 2012-000714-11
Status Terminated
Phase Phase 3
First received
Last updated
Start date January 22, 2013
Est. completion date May 30, 2018

Study information

Verified date February 2021
Source Bristol-Myers Squibb
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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)


Recruitment information / eligibility

Status Terminated
Enrollment 695
Est. completion date May 30, 2018
Est. primary completion date November 21, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility For additional information please contact the BMS Lupus Nephritis Clinical Trial Matching Service at 855-56-LUPUS. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Note: Subjects > 16 are eligible for enrollment at selected centers 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


Related Conditions & MeSH terms


Intervention

Biological:
BMS-188667

Drug:
Mycophenolate mofetil

Prednisone

Biological:
Placebo matching with BMS-188667


Locations

Country Name City State
Argentina Local Institution Buenos Aires
Argentina Local Institution Capital Federal Buenos Aires
Argentina Organizacion Medica De Investigacion S.A. (Omi) Capital Federal Buenos Aires
Argentina Hospital Privado-Centro Medico De Cordoba S.A. Cordoba
Australia Local Institution Adelaide South Australia
Australia Local Institution Parkville Victoria
Australia Local Institution Perth Western Australia
Brazil Local Institution Belo Horizonte Minas Gerais
Brazil Local Institution Goiania Goias
Brazil Local Institution Juiz De Fora Minas Gerais
Brazil Local Institution Porto Alegre Rio Grande Do Sul
Brazil Local Institution Sao Paulo
Brazil Local Institution Savaldor Bahia
Brazil Local Institution Uberlandia Minas Gerais
Canada Local Institution Mississauga Ontario
Canada Local Institution Toronto Ontario
Chile Local Institution Independencia Santiago
Chile Local Institution Santiago Metropolitana
Chile Local Institution Santiago De Chile Metropolitana
Chile Local Institution Vina Del Mar Valparaiso
China Local Institution Beijing Beijing
China Local Institution Beijing Beijing
China Local Institution Beijing
China Local Institution Chengdu Sichuan
China Local Institution Chong Qing
China Local Institution Guangzhou
China Local Institution Guangzhou Guangdong
China Local Institution Haikou Hainan
China Local Institution Hangzhou Zhejiang
China Local Institution Harbin Heilongjiang
China Local Institution Nanchang Jiangxi
China Local Institution Nanchang
China Local Institution Nanning
China Local Institution Shanghai
China Local Institution Shanghai
China Local Institution Shanghai
China Local Institution Shanghai Shanghai
China Local Institution Wuhan Hebei
China Local Institution Wuxi Jiangsu
China Local Institution Xi'An
China Local Institution Xian Shan1xi
China Local Institution Zhengzhou Henan
Colombia Circaribe S.A.S Barranquilla
Colombia Clinica De La Costa Barranquilla
Colombia Hospital Universitario San Ignacio Bogota
Colombia Riesgo De Fractura S.A. Cayre Ips Bogota Cundinamarca
Colombia Servimed E.U Bucaramanga Santander
Colombia Hospital Pablo Tobon Uribe Medellin
Czechia Local Institution Praha 2
Hong Kong Local Institution Hong Kong
India Local Institution Ahmedabad Gujrat
India Local Institution Gurgaon
India Local Institution Hyderabad
India Local Institution Lucknow-
India Local Institution New Delhi
India Local Institution Secunderabad Andhra Pradesh
Israel Local Institution Haifa
Israel Local Institution Haifa
Israel Local Institution Ramat-gan
Israel Local Institution Tel Aviv
Italy Local Institution Brescia
Italy Local Institution Milano
Italy Local Institution Padova
Italy Local Institution Reggio Emilia
Italy Local Institution Torino
Japan Local Institution Bunkyo-ku Tokyo
Japan Local Institution Bunkyo-ku Tokyo
Japan Local Institution Chiba-shi Chiba
Japan Local Institution Chuo-ku Tokyo
Japan Local Institution Fuchu Tokyo
Japan Local Institution Fukuoka-shi Fukuoka
Japan Local Institution Iruma-gun Saitama
Japan Local Institution Kanazawa-shi Ishikawa
Japan Local Institution Kita-gun
Japan Local Institution Kitakyushu-shi Fukuoka
Japan Local Institution Maebashi-shi Gunma
Japan Local Institution Nagakute-shi Aichi
Japan Local Institution Nagasaki-shi Nagasaki
Japan Local Institution Nagoya-shi Aichi
Japan Local Institution Niigata-shi Niigata
Japan Local Institution Okayama-shi Okayama
Japan Local Institution Osaka
Japan Local Institution Ota-ku Tokyo
Japan Local Institution Sapporo-shi Hokkaido
Japan Local Institution Sapporo-shi Hokkaido
Japan Local Institution Sendai-shi Miyagi
Japan Local Institution Shimotsuke-shi Tochigi
Japan Local Institution Shinjuku-Ku Tokyo
Japan Local Institution Yokohama-shi Kanagawa
Korea, Republic of Local Institution Daegu
Korea, Republic of Local Institution Seoul
Korea, Republic of Local Institution Seoul
Mexico Instituto Nacional De Ciencias Medicas Y Nutricion S.Z. Distrito Federal
Mexico Centro De Est D Inv. Basica Y Clinica Guadalajara Jalisco
Mexico Local Institution Guadalajara, Jalisco Jalisco
Mexico Centro Medico De Las Americas Merida Yucatan
Mexico Hospital De Jesus Mexico City Distrito Federal
Mexico Hospital General De Mexico O.D. Mexico City Distrito Federal
Mexico Local Institution Mexico City Distrito Fededral
Mexico Centro Potosino de Inv Clinica San Luis Potosi
Mexico Hosp Central I.Morones Prieto San Luis Potosi
Peru Hospital Nacional Cayetano Heredia Lima
Peru Hospital Nacional Guillermo Almenara Irigoyen Lima
Peru Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac Lima
Puerto Rico Local Institution San Juan
Romania Local Institution Bucharest
Romania Local Institution Bucuresti
Romania Local Institution Bucuresti
Romania Local Institution Cluj-napoca
Romania Local Institution Iasi
Russian Federation Local Institution Moscow
Russian Federation Local Institution St. Petersburg
Russian Federation Local Institution Ufa
Spain Local Institution Madrid
Spain Local Institution Madrid
Taiwan Local Institution Kaohsiung
Taiwan Local Institution Kaohsiung
Taiwan Local Institution Taichung
Taiwan Local Institution Taichung
Taiwan Local Institution Taipei
Taiwan Local Institution Taoyuan
Turkey Local Institution Antalya
Turkey Local Institution Edirne
United States Emory University. Atlanta Georgia
United States Ochsner Clinic Foundation Baton Rouge Louisiana
United States University Of Alabama At Birmingham (Uab) Birmingham Alabama
United States Boston University Medical Center Boston Massachusetts
United States Brigham & Women'S Hospital Boston Massachusetts
United States Suny Downstate Medical Center Brooklyn New York
United States Local Institution Camden New Jersey
United States University Of North Carolina At Chapel Hill Chapel Hill North Carolina
United States Local Institution Charlottesville Virginia
United States Rush University Medical Center Chicago Illinois
United States MetroHealth Medical Center Cleveland Ohio
United States UT Southwestern Medical Center Dallas Texas
United States University Of Connecticut Health Center Farmington Connecticut
United States Northshore Lij Health System Great Neck New York
United States Rheumatology Consultants Pllc Knoxville Tennessee
United States Valerius Med Group & Res Ctr Of Greater Long Beach, Inc. Long Beach California
United States The Feinstein Institute For Medical Research Manhasset New York
United States University Of Miami Miller School Of Medicine Miami Florida
United States Paramount Medical Research & Consulting, Llc Middleburg Heights Ohio
United States Tulane University School Of Medicine New Orleans Louisiana
United States Hospital For Special Surgery New York New York
United States Local Institution New York New York
United States Integral Rheumatology & Immunology Specialists Plantation Florida
United States Shanahan Rheum & Immunotherapy, PLLC Raleigh North Carolina
United States University Of Utah Hospital Salt Lake City Utah
United States East Bay Rheumatology Medical Group, Inc. San Leandro California

Sponsors (1)

Lead Sponsor Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Taiwan,  Turkey, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period 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. Day 365
Secondary Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period 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. Day 365
Secondary Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (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 nephrotic participants Baseline and Day 365
Secondary Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population Adjusted Mean Change from Baseline in Urine protein/creatinine ratio (UPCR) at Day 365 of the double-blind period in the overall population Day 1 and Day 365
Secondary Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period 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. Day 1 to Day 365
Secondary Number of Participants With Any Adverse Events (AEs) During 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. From Day 1 up to 56 days post last dose in Year 1 of the double-blind period
Secondary Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period 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 Day 365, Day 729
Secondary Median Time to Complete Renal Response During the Double-blind Period in All Participants 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. Day 365, Day 729
Secondary Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants 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. Day 365, Day 729
Secondary Median Time to Partial Renal Response During the Double-blind Period in All Participants 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 Day 365, Day 729
Secondary Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants 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 Day 365, Day 729
Secondary Adjusted Mean Change From Baseline in UPCR Over Time 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. Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended
Secondary Median Percent Change From Baseline in UPCR Over Time 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
Day 365, Day 729
Secondary Adjusted Mean Change From Baseline in eGFR Over Time 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)a 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, a 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. Day 365, Day 729
Secondary Median Time to First Sustained Change to No Response During the Double-blind Period 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
Day 365, Day 729
Secondary Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period 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. Day 365, Day 729
Secondary Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period 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. Day 1 to Day 729; Day 365 to Day 729
Secondary Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion Trough level serum concentration of abatacept prior to the administration of the IV infusion on Days 1 to 365 Days 1 to 365
Secondary Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV 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
Secondary AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval AUC (TAU): Area under the serum concentration time curve over a dosing interval between Days 337 to 365. Days 337 to 365
Secondary Summary Statistics for Systolic Blood Pressure Summary statistics for systolic blood pressure Day 1 to Day 729
Secondary Summary Statistics for Diastolic Blood Pressure Summary statistics for diastolic blood pressure Day 1 to Day 729
Secondary Summary Statistics for Heart Rate Summary statistics for Heart Rate Day 1 to Day 729
Secondary Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L) 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.
Day 729
Secondary Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L) 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.
Day 729
Secondary Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood) 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.
Day 729
Secondary Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L) 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.
Day 729
Secondary Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L) 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.
Day 729
Secondary Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L) 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.
Day 729
Secondary Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period 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 RXN = the number of participants with at least 1 on treatment lab result for each analyte 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
Secondary Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period 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
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
Secondary Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period 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 RXN = the number of participants with at least 1 on treatment lab result for each analyte 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
Secondary Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period 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 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
Secondary Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period 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 RXN = the number of participants with at least 1 on treatment lab result for each analyte 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
Secondary Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension 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. From the first dose in Year 2 of the double-blind period up to 56 days post last dose
Secondary Percentage of Participants in Treatment Failure Over Time During the Double-blind Period 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.
Day 365, Day 729
Secondary Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period 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
Day 365, Day 729
Secondary Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period 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. Day 729
Secondary Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period 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. Day 729
Secondary Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period 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 RXN = the number of participants with at least 1 on treatment lab result for each analyte Day 1 to Day 729
Secondary Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period 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
Day 1 to Day 729
Secondary Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period 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 RXN = the number of participants with at least 1 on treatment lab result for each analyte Day 1 to Day 729
Secondary Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period 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 Day 1 to Day 729
Secondary Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period 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 RXN = the number of participants with at least 1 on treatment lab result for each analyte Day 1 to Day 729
Secondary Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period Participants who experienced a positive antibody response relative to baseline (ECL Assay) Day 365, Day 729
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