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Trial record 6 of 137 for:    "Connective Tissue Disease" | "Abatacept"

Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00430677
Recruitment Status : Terminated (Terminated due to failure to meet the primary efficacy endpoint in the Short-term Period)
First Posted : February 2, 2007
Results First Posted : May 11, 2012
Last Update Posted : March 20, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: Corticosteroids (prednisone or prednisolone) Drug: Abatacept Drug: Mycophenolate mofetil (MMF) Phase 2 Phase 3

Detailed Description:

Double Blind Period: Treatment, Parallel Assignment, Double Blind (Subject, Investigator), Randomized, Active Control, Safety/Efficacy Study

Open Label Period: Prevention, Single Group Assignment, Open Label, Uncontrolled, Safety/Efficacy Study


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 423 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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)
Study Start Date : June 2007
Actual Primary Completion Date : September 2010
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus
Drug Information available for: Abatacept

Arm Intervention/treatment
Experimental: Abatacept 30 mg/kg+Corticosteroids+MMF
Short-term Period
Drug: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily

Drug: Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days
Other Names:
  • Orencia
  • BMS-188667

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

Experimental: Abatacept 10 mg/kg+Corticosteroids+MMF
Short-term Period
Drug: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily

Drug: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days
Other Names:
  • Orencia
  • BMS-188667

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

Experimental: Placebo+Corticosteroids+MMF
Short-term Period
Drug: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily

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

Experimental: Abatacept 10mg/kg
Long-term Extension Period
Drug: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days




Primary Outcome Measures :
  1. Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period [ Time Frame: Day 1 (randomization) to 12 months. ]
    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.


Secondary Outcome Measures :
  1. Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period [ Time Frame: Day 1 to 12 months ]
    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.

  2. Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period [ Time Frame: At Month 12 from Day 1 ]
    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.

  3. Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology) [ Time Frame: Day 1 (randomization) to 12 months. ]
    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.

  4. Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period [ Time Frame: At Month 12 from Day 1 ]
    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.

  5. Number of Months CRR Was Maintained During Short-term Period [ Time Frame: Day 1 (randomization) to 12 Months ]
    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.

  6. Baseline Renal Function Over Time During Short-term Period [ Time Frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 ]
    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.

  7. Change in Renal Function From Baseline Over Time During Short-term Period [ Time Frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365 ]
    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.

  8. Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period [ Time Frame: Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose) ]
    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.

  9. Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period [ Time Frame: Month 12 ]
    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.

  10. Change in SLICC/ACR Damage Index From Baseline During Short-term Period [ Time Frame: Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose) ]
    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.

  11. Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  12. Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  13. Baseline Mental Component Summary of the Short SF-36 During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  14. Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  15. Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  16. Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]

    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.


  17. Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  18. Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ]
    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.

  19. Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period [ Time Frame: 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. ]
    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.

  20. Participants With AEs of Special Interest During the Short-term Period [ Time Frame: 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. ]
    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.

  21. Participants With Marked Hematology Abnormalities During the Short-term Period [ Time Frame: 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. ]
    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.

  22. Participants With Marked Laboratory Abnormalities During the Short-term Period [ Time Frame: 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. ]
    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

  23. Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period [ Time Frame: 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. ]

    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.


  24. Participants With Marked Abnormalities Urinalysis During the Short-term Period [ Time Frame: 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. ]
    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).

  25. Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP) [ Time Frame: 0 - 12 Months ]
  26. Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP) [ Time Frame: 0 - 12 Months ]
  27. Vital Signs Summary During the Short-term Period: Heart Rate [ Time Frame: 0 - 12 Months ]
  28. Vital Signs Summary During the Short-term Period: Temperature [ Time Frame: 0 - 12 Months ]
  29. Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period [ Time Frame: Day 169, Day 365 ]
    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.

  30. Baseline Quantitative Immunoglobulins During the Short-term Period [ Time Frame: Baseline (Day 1) ]
    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.

  31. Change in Quantitative Immunoglobulin From Baseline During Short-term Period [ Time Frame: Day 365 ]

    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


  32. Number of Participants Achieving Complete Response by ACCESS Definition [ Time Frame: End of short-term period (Day 365) to termination of the long-term extension period ]
    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.

  33. 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 [ Time Frame: At Day 365 (end of Short-term Period) and Day 645 ]
    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.

  34. Mean Change From Baseline in SLICC/ACR Damage Index [ Time Frame: Day 365 to termination of the long-term extension phase ]
    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.

  35. 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 [ Time Frame: 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. ]
    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.

  36. Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period [ Time Frame: Day 365 to end of 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

  37. Number of Participants Achieving Renal Response [ Time Frame: At Day 365 (end of short-term period) and Day 645 ]
    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.

  38. Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period [ Time Frame: From start of study drug on Day 365 up to 56 days after last dose in 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.

  39. Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued) [ Time Frame: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period ]
    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.

  40. Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued) [ Time Frame: From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period ]
    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.


Other Outcome Measures:
  1. Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period [ Time Frame: Month 12 ]

    PR is either CRR, Partial Renal Response(PRR),or no Response(NR).

    CRR= Serum creatinine(SC)is normal, Inactive urinary sediment, No cellular casts, Urinary protein/creatinine (UPCR) ratio <56.5 mg/mmoL; PRR= SC is normal OR SC not >25% above BL, 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 BL ratio; NR= Not achieving either a CRR or a PRR. Participants achieved response if criteria at both months 11 and 12 (Days 337 and 365) were met. Participants who Early discontinuations were categorized as NR.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00430677


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Locations
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United States, Alabama
University Of Alabama At Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Arizona Arthritis Center
Tucson, Arizona, United States, 85724
United States, California
Wallace Rheumatic Study Center
Los Angeles, California, United States, 90048
United States, Kansas
University Of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston University School Of Medicine
Boston, Massachusetts, United States, 02118
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
United States, New York
Suny Downstate Medical Center
Brooklyn, New York, United States, 11203
Northshore Lij Health System
Lake Success, New York, United States, 11042
The Feinstein Institute For Medical Research
Manhasset, New York, United States, 11030
Suny Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
University Of North Carolina At Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Oklahoma
Ok Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Rheumatology Consultants Pllc
Knoxville, Tennessee, United States, 37909
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Argentina
Local Institution
Capital Federal, Buenos Aires, Argentina, 1015
Local Institution
Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1055
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Cordoba, Argentina, 5016
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Tucuman, Argentina, 4000
Australia, New South Wales
Local Institution
Liverpool, New South Wales, Australia, 2170
Australia, Victoria
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Clayton, Victoria, Australia, 3168
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Heidelberg, Victoria, Australia, 3084
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Parkville, Victoria, Australia, 3050
Belgium
Local Institution
Bruxelles, Belgium, 1200
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Leuven, Belgium, 3000
Brazil
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Goiania, Goias, Brazil, 74110
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Curitiba, Parana, Brazil, 80060
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Porto Alegre, Rio Grande Do Sul, Brazil, 91610
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Rio De Janeiro, Brazil, 20551
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Sao Paulo, Brazil, 04026
Canada, Alberta
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Edmonton, Alberta, Canada, T6G 2S2
Canada, Manitoba
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Winnipeg, Manitoba, Canada, R3A 1M4
Canada, Ontario
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Toronto, Ontario, Canada, M5T 2S8
Canada
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Quebec, Canada, G1R 2J6
China, Beijing
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Beijing, Beijing, China, 100034
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Beijing, Beijing, China, 100044
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Beijing, Beijing, China, 100730
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Beijing, Beijing, China, 100853
China, Guangdong
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Guangzhou, Guangdong, China, 510080
China, Shanghai
Local Institution
Shanghai, Shanghai, China, 200001
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Shanghai, Shanghai, China, 200025
China, Shanxi
Local Institution
Xi'an, Shanxi, China, 710032
France
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Creteil Cedex, France, 94010
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Paris Cedex 13, France, 75651
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Strasbourg Cedex, France, 67098
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Toulouse Cedex 4, France, 31403
Hong Kong
Local Institution
Hong Kong, Hong Kong
India
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Gujarat, Ahmedabad, India, 380016
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Secunderabad, Andhra Pradesh, India, 500003
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Ahmedabad, Gujarat, India, 380 007
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Nadiad, Gujarat, India, 387001
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Bangalore, Karnataka, India, 560 017
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Bangalore, Karnataka, India, 560 034
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Kochi, Kerala, India, 682026
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Mumbai, Maharajhsra, India, 400064
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Hyderabad, India, 500082
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Visakhapatnam, India, 530002
Korea, Republic of
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Seoul, Sungdong-Gu, Korea, Republic of, 133-792
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Seoul, Korea, Republic of, 110-744
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Seoul, Korea, Republic of, 137-040
Mexico
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Mexico City, Distrito Federal, Mexico, 06726
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Metepec, Estado De Mexico, Mexico, 52140
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Guadalajara, Jalisco, Mexico, 44100
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Guadalajara, Jalisco, Mexico, 44690
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Monterrey, Nuevo Leon, Mexico, 64020
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Merida, Yucatan, Mexico, 97000
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Aguascalientes, Mexico, 20000
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San Luis Potosi, Mexico, 78240
Poland
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Bydgoszcz, Poland, 85-094
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Gdansk, Poland, 80-952
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Wroclaw, Poland, 50-417
Russian Federation
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Ekaterinburg, Russian Federation, 620102
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Moscow, Russian Federation, 115522
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Yaroslaval, Russian Federation, 150062
South Africa
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Johannesburg, Gauteng, South Africa, 2013
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Observatory, Western Cape, South Africa, 7925
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Panorama, Western Cape, South Africa, 7500
Taiwan
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Kaohsiung, Taiwan, 833
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Taichung, Taiwan, 402
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Taichung, Taiwan, 407
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Taipei, Taiwan, 11217
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Taoyuan, Taiwan, 333
Turkey
Local Institution
Gaziantep, Turkey, 27310
United Kingdom
Local Institution
Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
Local Institution
London, Greater London, United Kingdom, SE1 7EX
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00430677     History of Changes
Other Study ID Numbers: IM101-075
First Posted: February 2, 2007    Key Record Dates
Results First Posted: May 11, 2012
Last Update Posted: March 20, 2015
Last Verified: March 2015

Additional relevant MeSH terms:
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Connective Tissue Diseases
Abatacept
Lupus Erythematosus, Systemic
Autoimmune Diseases
Immune System Diseases
Prednisone
Prednisolone
Mycophenolic Acid
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents