Please note that the ANZCTR website will be unavailable from 9am until 9.30am (AEST) on Monday 22nd July for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00430677




Registration number
NCT00430677
Ethics application status
Date submitted
1/02/2007
Date registered
2/02/2007
Date last updated
20/03/2015

Titles & IDs
Public title
Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis
Scientific title
A Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects With Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE)
Secondary ID [1] 0 0
IM101-075
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Corticosteroids (prednisone or prednisolone)
Treatment: Drugs - Abatacept
Treatment: Drugs - Abatacept
Treatment: Drugs - Mycophenolate mofetil (MMF)
Treatment: Drugs - Abatacept

Experimental: Abatacept 30 mg/kg+Corticosteroids+MMF - Short-term Period

Experimental: Abatacept 10 mg/kg+Corticosteroids+MMF - Short-term Period

Experimental: Placebo+Corticosteroids+MMF - Short-term Period

Experimental: Abatacept 10mg/kg - Long-term Extension Period


Treatment: Drugs: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily

Treatment: Drugs: Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days

Treatment: Drugs: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days

Treatment: Drugs: Mycophenolate mofetil (MMF)
tablets, oral, 1.5 to 2 g, daily

Treatment: Drugs: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period - Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
Timepoint [1] 0 0
Day 1 (randomization) to 12 months.
Secondary outcome [1] 0 0
Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period - Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
Timepoint [1] 0 0
Day 1 to 12 months
Secondary outcome [2] 0 0
Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period - Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
Timepoint [2] 0 0
At Month 12 from Day 1
Secondary outcome [3] 0 0
Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology) - RI is defined as meeting all of the following criteria. Renal function: If MDRD is abnormal at screening, within 10% of the MDRD at screening; if MDRD is 60-89 at screening, greater than or equal to 50% improvement based on the screening value or 90% or greater of MDRD at screening; if MDRD is 15-59 at screening, if MDRD is normal at screening-within 10% of the MDRD at screening. Proteinuria: improvement greater than or equal to 50% from screening. Hematuria: red blood cell (RBC)count within normal limit of central laboratory. Pyuria: white blood cell (WBC) count within normal limit of central laboratory. Cylindruria: No RBC or WBC casts.
Timepoint [3] 0 0
Day 1 (randomization) to 12 months.
Secondary outcome [4] 0 0
Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period - CRR defined as meeting all of 5 criteria. RF: (Glomerular filtration rate [GFR] calculated using MDRD equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
Timepoint [4] 0 0
At Month 12 from Day 1
Secondary outcome [5] 0 0
Number of Months CRR Was Maintained During Short-term Period - Durability of CRR, defined as the number of months (number of consecutive planned visits beyond Day 15) a participant met the definition of CRR during the double-blind treatment period. Refer to outcome 1 for description of CRR.
Timepoint [5] 0 0
Day 1 (randomization) to 12 Months
Secondary outcome [6] 0 0
Baseline Renal Function Over Time During Short-term Period - Baseline (BL) renal function, as estimated by calculation of the MDRD (Modification of Diet in Renal Disease) equation, over time. Renal MDRD is an equation (calculation) used to estimate Glomerular Filtration Rate (GFR) in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine. A negative value indicates worsening.
Timepoint [6] 0 0
Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Secondary outcome [7] 0 0
Change in Renal Function From Baseline Over Time During Short-term Period - Mean change from baseline in renal function, as estimated by calculation of the MDRD equation, over time. Renal MDRD is an equation (calculation) used to estimate Glomerular Filtration Rate (GFR) in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine. A positive value indicates improvement. Change from baseline=Post-baseline-baseline value.
Timepoint [7] 0 0
Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Secondary outcome [8] 0 0
Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period - SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as nonreversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as =1. The total maximum score is 48, and increasing score indicates increasing disease severity.
Timepoint [8] 0 0
Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)
Secondary outcome [9] 0 0
Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period - RR is defined as meeting BOTH of the following criteria:RENAL FUNCTION: Less than or equal to 25% increase from baseline;PROTEINURIA: Greater than or equal to 50% improvement in the urine protein/creatinine ratio with one of the following - urine protein/creatinine ratio (UPCR) <113 mg/mmol,, if the baseline ratio was <=339 mg/mmol OR UPCR <339 mg/mmol,if the baseline ratio > 339 mg/mmol. A participant was considered as achieving RR if response criteria at both months 11 and 12 (Days 337 and 365, respectively) were met. For 95% CI within each group, normal approximation is used if n>=5.
Timepoint [9] 0 0
Month 12
Secondary outcome [10] 0 0
Change in SLICC/ACR Damage Index From Baseline During Short-term Period - SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as =1. The total maximum score is 48, and increasing score indicates increasing disease severity. Change from baseline=Postbaseline - baseline value.
Timepoint [10] 0 0
Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)
Secondary outcome [11] 0 0
Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period - The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Timepoint [11] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [12] 0 0
Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period - The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Timepoint [12] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [13] 0 0
Baseline Mental Component Summary of the Short SF-36 During Short-term Period - The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Timepoint [13] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [14] 0 0
Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period - The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Timepoint [14] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [15] 0 0
Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period - A visual analogue scale (VAS) is a psychometric response scale for measurement of subjective characteristics or attitudes that cannot be directly measured. The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Timepoint [15] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [16] 0 0
Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period - A visual analogue scale is a psychometric response scale for measurement of subjective characteristics or attitudes that cannot be directly measured.
The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Timepoint [16] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [17] 0 0
Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period - The reduction of fatigue assessed by Fatigue Severity Scale (FSS). The FSS questionnaire is comprised of 9 statements inquiring about the examinee's sleep habits over the preceding week. Participants are asked to rate their level of agreement (toward seven) or disagreement (toward zero) with the nine statements. A score of 36 and above (out of a maximum of 63) indicates the presence of significant fatigue.
Timepoint [17] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [18] 0 0
Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period - The reduction of fatigue assessed by Fatigue Severity Scale (FSS). The FSS questionnaire is comprised of 9 statements inquiring about the examinee's sleep habits over the preceding week. Participants are asked to rate their level of agreement (toward seven) or disagreement (toward zero) with the nine statements. A score of 36 and above (out of a maximum of 63) indicates the presence of significant fatigue.
Timepoint [18] 0 0
Baseline (Day 1), Days 85, 169, 253, and 365
Secondary outcome [19] 0 0
Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period - AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=possibly, probably, or certainly related to and of unknown relationship to study drug.
Timepoint [19] 0 0
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Secondary outcome [20] 0 0
Participants With AEs of Special Interest During the Short-term Period - AEs of special interest were prospectively identified to be those that may be associated with the use of immunomodulatory agents. They are a subset of all AEs and may be either serious or non-serious.
Timepoint [20] 0 0
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Secondary outcome [21] 0 0
Participants With Marked Hematology Abnormalities During the Short-term Period - LLN=lower limit of normal; ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age. Low(?)Hemoglobin:>3g/dL decrease from PTV; ?Hematocrit:<0.75xPTV;?Erythrocyte count:<0.75xPTV; high(?)Platelet count:>1.5xULN;?Platelet count:<0.67xLLN;?Leukocyte count:<0.75X LLN;?Leukocyte count:>1.25xULN;?Absolute(AB)Neutrophils+Bands:<1.00x10^3c/uL;?AB Lymphocyte count:>7.50x10^3 c/uL; ?AB lymphocyte count:<0.750x10^3 c/uL;?AB monocyte count:>2000/mm^3;?AB basophil count:>400/mm^3;?AB eosinophil count:>0.750x10^3 c/uL.
Timepoint [21] 0 0
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Secondary outcome [22] 0 0
Participants With Marked Laboratory Abnormalities During the Short-term Period - LLN=lower limit of normal; ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age. ?Serum Sodium:>1.05x ULN;?Serum Potassium:<0.9x LLN;?Serum Potassium:>1.1x ULN;?Total Calcium:<0.8X LLN;?Total Calcium:>1.2x ULN; ?Serum Glucose(SG):<65 mg/dL;?SG:>220 mg/dL;?Fasting SG:<0.8x LLN;?Fasting SG:>1.5x ULN;?Total Protein:<0.9x LLN;?Albumin:<0.9x LLN;?Total Cholesterol:>2x PTV;?Triglycerides:>=2.5x ULN;?Fasting Triglycerides:>=2x ULN
Timepoint [22] 0 0
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Secondary outcome [23] 0 0
Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period - ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age.
Alkaline Phosphatase:>2x ULN; ?Aspartate Aminotransferase: >3x ULN; ?Alanine Aminotransferase : >3x ULN; G-Glutamyl Transferase : >2x ULN; ?Total Bilirubin : >2x ULN or if PTV > ULN then > 4x PTV; ?Blood Urea Nitrogen >2x PTV; ?Creatinine >1.5x PTV.
Timepoint [23] 0 0
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Secondary outcome [24] 0 0
Participants With Marked Abnormalities Urinalysis During the Short-term Period - PTV=pretreatment value. Criteria for marked abnormality: Protein, glucose, blood, leukocyte esterase , if missing PTV then use >=2+ (or, if value >=4, or if PTV=0 or 0.5, >=2 or if PTV=1, >=3, or if PTV=2 or 3, >=4).
Timepoint [24] 0 0
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Secondary outcome [25] 0 0
Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP)
Timepoint [25] 0 0
0 - 12 Months
Secondary outcome [26] 0 0
Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP)
Timepoint [26] 0 0
0 - 12 Months
Secondary outcome [27] 0 0
Vital Signs Summary During the Short-term Period: Heart Rate
Timepoint [27] 0 0
0 - 12 Months
Secondary outcome [28] 0 0
Vital Signs Summary During the Short-term Period: Temperature
Timepoint [28] 0 0
0 - 12 Months
Secondary outcome [29] 0 0
Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period - A validated, sensitive electrochemiluminescence (ECL) immunoassay based on Meso-Scale Discovery instrumentation was used to evaluate immunogenicity. The ECL assay differentiated between two antibody specificities: (1) the 'Ig and/or Junction (Jn) Region' and (2) 'CLTA4 and possibly Ig'. A sample was considered positive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept with or without CTLA4-T.
Timepoint [29] 0 0
Day 169, Day 365
Secondary outcome [30] 0 0
Baseline Quantitative Immunoglobulins During the Short-term Period - A quantitative immunoglobulins (Igs) test is used to detect abnormal levels of the three major classes of Igs (IgG, IgA, and IgM). Abnormal test results typically indicate that there is something affecting the immune system which requires further testing.
Timepoint [30] 0 0
Baseline (Day 1)
Secondary outcome [31] 0 0
Change in Quantitative Immunoglobulin From Baseline During Short-term Period - A quantitative immunoglobulin (Ig) test is used to detect abnormal levels of the 3 major classes of Ig (IgG, IgA, and IgM). Abnormal test results typically indicate that something is affecting the immune system and further testing is required.
Please refer to Outcome 31 for the respective baseline values
Timepoint [31] 0 0
Day 365
Secondary outcome [32] 0 0
Number of Participants Achieving Complete Response by ACCESS Definition - The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) defines complete response as a response meeting all of the following criteria: serum creatinine =upper limit of normal as defined by the central laboratory or =125% of the higher value at either screening or baseline; urine protein/creatinine ratio <50 mg/mmoL; and prednisone or prednisone-equivalent dose tapered to 10 mg per day.
Timepoint [32] 0 0
End of short-term period (Day 365) to termination of the long-term extension period
Secondary outcome [33] 0 0
Number of Participants Achieving Patient Response of Complete or Partial Response, Based on the June 2010 Food and Drug Administration Guidance Document for Lupus Nephritis - Patient response=complete, partial, or no response. Complete response=serum creatinine (SCr) normal, inactive urinary sediment, no cellular casts, urinary protein/creatinine (UPCR) ratio<56.5 mg/mmol. Partial response=SCr normal or =25% above baseline value, RBCs at reference range, UPCR <56.5 mg/mmoL OR =50% improvement in UPCR with one of the following: UPCR <113 or <339 mg/mmoL, based on the baseline ratio. No response=Not achieving complete or partial response criteria.
Timepoint [33] 0 0
At Day 365 (end of Short-term Period) and Day 645
Secondary outcome [34] 0 0
Mean Change From Baseline in SLICC/ACR Damage Index - SLICC=Systemic Lupus International Collaborating Clinics; ACR=American College of Rheumatology. The SLICC/ACR Damage Index measures organ damage (nonreversible change, unrelated to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months unless otherwise stated. The index assesses 47 items in 12 systems: Ocular, Neuropsychiatric, Renal, Pulmonary, Cardiovascular, Gastrointestinal, Peripheral Vascular, Musculoskeletal, Skin, Premature Gonadal Failure, Diabetes, Malignancy. Scores range from 0 to 2, and the same lesion cannot be scored twice. If damage is noted for a particular item, it is scored 1. No damage is scored 0. Some items may score 2 points if they occur more than once, so that the maximum possible score is 47. Scores can only increase with time, but scores rarely reach over 12. It is usually completed (or updated) yearly.
Timepoint [34] 0 0
Day 365 to termination of the long-term extension phase
Secondary outcome [35] 0 0
Number of Participants With Death, Serious Adverse Events (SAE), Treatment-related Adverse Events SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs During Long-term Extension Period - AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=possibly, probably, or certainly related to and of unknown relationship to study drug.
Timepoint [35] 0 0
From start of study drug in long-term period (Day 365) to up to 56 days after the last dose of the long-term extension (LTE). Deaths in LTE reported to >56 days post last dose.
Secondary outcome [36] 0 0
Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period - Collected in at least 1 sample. Assessment includes immunogenicity (detection of serum antibodies which bind to CTLA4-Ig in the in vitro assays) and exposure to corticosteroids
Timepoint [36] 0 0
Day 365 to end of long-term extension period
Secondary outcome [37] 0 0
Number of Participants Achieving Renal Response - Renal response=serum creatinine level =25% above baseline value and greater than or equal to 50% improvement in the urine protein/creatinine ratio with 1 of the following: urine protein/creatinine ratio (UPCR) <113 mg/mmol, if the baseline ratio was <= 339 mg/mmol OR UPCR <339 mg/mmol,if the baseline ratio >339 mg/mmol.
Timepoint [37] 0 0
At Day 365 (end of short-term period) and Day 645
Secondary outcome [38] 0 0
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period - preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Hemoglobin (g/dL): >3g/dL decrease from preRX value. Hematocrit(%): <0.75*preRX. Erythrocytes (*10^6 c/uL): <0.75*preRX. Platelet count (*10^9 c/L): <0.67*LLN, or >1.5*ULN, or if preRX <LLN, use <0.5*preRX and <100,000/mm^3. Leukocytes (*10^3 c/uL): <0.75*LLN or >1.25*ULN, or if preRX <LLN, use <0.8* preRX or >ULN; if preRX>ULN, use >1.2*preRX or <LLN. Neutrophils + Bands (absolute) (*10^3 c/uL): If value <1.0*10^3 or if value >7.50*10^3 c/uL. Monocytes (absolute) (*10^3 c/uL): If value >2000/mm^3. Basophils (absolute)(*10^3 c/uL): If value >.750*10^3 c/uL. Eosinophils (absolute) (*10^3 c/uL): If value >.750*10^3 c/uL. ALP (U/L): >2*ULN, or if preRX>ULN, use >3* preRX. AST (U/L): >3*ULN, or if preRX>ULN, use >4*preRX. ALT (U/L): >3*ULN, or if preRX>ULN, use >4*preRX. GGT (U/L):>2*ULN, or if preRX >ULN, use >3*preRX. Bilirubin, total (mg/dL): >2*ULN, or if preRX>ULN, use >4*preRX. BUN (mg/dL): >1.5*preRX.
Timepoint [38] 0 0
From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
Secondary outcome [39] 0 0
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued) - LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Sodium, serum (mEq/L): <0.95*LLN or >1.05*ULN, or if preRX<LLN, use <0.95*preRX or >ULN if preRX>ULN, use >1.05*preRX or <LLN. Potassium, serum (mEq/L): <0.9* LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN. Chloride, serum (mEq/L): <0.9*LLN or >1.1*ULN, or if preRX<LLN, use <0.9*preRX or >ULN. Calcium, total (mg/dL): <0.8*LLN or >1.2*ULN, or if preRX<LLN, use <0.75*preRX or >ULN if preRX>ULN, use >1.25*preRX or <LLN. Glucose, serum (mg/dL): <65 mg/dL, or >220 mg/dL. Glucose, fasting serum (mg/dL): <0.8*LLN or >1.5*ULN, or if preRX <LLN, use <0.8*preRX or >ULN if preRX>ULN, use >2.0*preRX or <LLN. Albumin (g/dL): <0.9*LLN, or if preRX <LLN, use <0.75*preRX. Cholesterol, total (mg/dL): >2*preRX. Triglycerides (mg/dL): >=2.5*ULN, or if preRX>ULN, use >=2.5*preRX. Triglycerides, fasting (mg/dL): >=2*ULN, or if preRX>ULN, use >2.0*preRX.
Timepoint [39] 0 0
From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
Secondary outcome [40] 0 0
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued) - preRX=pretreatment. Protein, urine: If missing preRX, use >=2, or if value >=4, or if preRX =0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 OR 3 then use >=4. Glucose, urine: If missing preRX, use >=2, or if value >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4. Blood, urine: If missing preRX, use >=2, or if value >=4, or if preRX =0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4. Leukocyte esterase, urine: If missing preRX, use >=2, or if value >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4.
Timepoint [40] 0 0
From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period

Eligibility
Key inclusion criteria
- Systemic Lupus Erythematosus (SLE) as defined by meeting at least 4 of the 11
classification criteria of the American College of Rheumatology for the classification
of Systemic Lupus Erythematosus, either sequentially or coincident. The 4 criteria
need not be present at study entry

- Renal biopsy within 12 months prior to screening visit indicating active proliferative
lupus glomerulonephritis (met ISN/RPS Class III or IV classification criteria [2003],
excluding Class III [C], IV-S [C] and IV-G [C], or the World Health Organization Class
III or IV classification criteria [1982], excluding Class IIIc, IVd). If the renal
biopsy was performed >3 months but =12 months prior to screening visit, at least 1 of
the following 3 serologies (performed locally) must have been abnormal prior to
screening visit: complement (C3 or C4) level below normal range OR anti-dsDNA >upper
limit of normal range.

- A stable serum creatinine =3 mg/dL
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects with a rise in serum creatinine of =1 mg/dL within 1 month prior to the
screening visit

- Subjects with drug-induced SLE, as opposed to idiopathic SLE

- Subjects with severe, unstable and/or progressive Central nervous system (CNS) lupus

- Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.;
Rheumatoid arthritis (RA), Multiple Sclerosis [MS])

- Subjects who have received treatment with cyclophosphamide within 3 months of
randomization (Day 1).

- Subjects who have received treatment with rituximab < 6 months prior to the screening
visit

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Local Institution - Liverpool
Recruitment hospital [2] 0 0
Local Institution - Clayton
Recruitment hospital [3] 0 0
Local Institution - Heidelberg
Recruitment hospital [4] 0 0
Local Institution - Parkville
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
Cordoba
Country [14] 0 0
Argentina
State/province [14] 0 0
Tucuman
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Brazil
State/province [17] 0 0
Goias
Country [18] 0 0
Brazil
State/province [18] 0 0
Parana
Country [19] 0 0
Brazil
State/province [19] 0 0
Rio Grande Do Sul
Country [20] 0 0
Brazil
State/province [20] 0 0
Rio De Janeiro
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
Manitoba
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Guangdong
Country [28] 0 0
China
State/province [28] 0 0
Shanghai
Country [29] 0 0
China
State/province [29] 0 0
Shanxi
Country [30] 0 0
France
State/province [30] 0 0
Creteil Cedex
Country [31] 0 0
France
State/province [31] 0 0
Paris Cedex 13
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg Cedex
Country [33] 0 0
France
State/province [33] 0 0
Toulouse Cedex 4
Country [34] 0 0
Hong Kong
State/province [34] 0 0
Hong Kong
Country [35] 0 0
India
State/province [35] 0 0
Ahmedabad
Country [36] 0 0
India
State/province [36] 0 0
Andhra Pradesh
Country [37] 0 0
India
State/province [37] 0 0
Gujarat
Country [38] 0 0
India
State/province [38] 0 0
Karnataka
Country [39] 0 0
India
State/province [39] 0 0
Kerala
Country [40] 0 0
India
State/province [40] 0 0
Maharajhsra
Country [41] 0 0
India
State/province [41] 0 0
Hyderabad
Country [42] 0 0
India
State/province [42] 0 0
Visakhapatnam
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Sungdong-Gu
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seoul
Country [45] 0 0
Mexico
State/province [45] 0 0
Distrito Federal
Country [46] 0 0
Mexico
State/province [46] 0 0
Estado De Mexico
Country [47] 0 0
Mexico
State/province [47] 0 0
Jalisco
Country [48] 0 0
Mexico
State/province [48] 0 0
Nuevo Leon
Country [49] 0 0
Mexico
State/province [49] 0 0
Yucatan
Country [50] 0 0
Mexico
State/province [50] 0 0
Aguascalientes
Country [51] 0 0
Mexico
State/province [51] 0 0
San Luis Potosi
Country [52] 0 0
Poland
State/province [52] 0 0
Bydgoszcz
Country [53] 0 0
Poland
State/province [53] 0 0
Gdansk
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Ekaterinburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Moscow
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Yaroslaval
Country [58] 0 0
South Africa
State/province [58] 0 0
Gauteng
Country [59] 0 0
South Africa
State/province [59] 0 0
Western Cape
Country [60] 0 0
Taiwan
State/province [60] 0 0
Kaohsiung
Country [61] 0 0
Taiwan
State/province [61] 0 0
Taichung
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taipei
Country [63] 0 0
Taiwan
State/province [63] 0 0
Taoyuan
Country [64] 0 0
Turkey
State/province [64] 0 0
Gaziantep
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Cambridgeshire
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this clinical research study is to learn if addition of abatacept is safe and
improves the effectiveness of treatment of patients with active lupus nephritis who are also
taking mycophenolate mofetil (MMF) and corticosteroids.
Trial website
https://clinicaltrials.gov/show/NCT00430677
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00430677