Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

This study has been terminated.
(Terminated due to failure to meet the primary efficacy endpoint in the Short-term Period)
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00430677
First received: February 1, 2007
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period [ Time Frame: Day 1 (randomization) to 12 months. ] [ Designated as safety issue: No ]
    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:
  • Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period [ Time Frame: Day 1 to 12 months ] [ Designated as safety issue: No ]
    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.

  • Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period [ Time Frame: At Month 12 from Day 1 ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]
    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.

  • Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period [ Time Frame: At Month 12 from Day 1 ] [ Designated as safety issue: No ]
    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.

  • Number of Months CRR Was Maintained During Short-term Period [ Time Frame: Day 1 (randomization) to 12 Months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Baseline Mental Component Summary of the Short SF-36 During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]

    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.


  • Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period [ Time Frame: Baseline (Day 1), Days 85, 169, 253, and 365 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: Yes ]
    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.

  • 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. ] [ Designated as safety issue: Yes ]
    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.

  • 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. ] [ Designated as safety issue: Yes ]
    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.

  • 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. ] [ Designated as safety issue: Yes ]
    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

  • 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. ] [ Designated as safety issue: Yes ]

    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.


  • 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. ] [ Designated as safety issue: Yes ]
    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).

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

  • Baseline Quantitative Immunoglobulins During the Short-term Period [ Time Frame: Baseline (Day 1) ] [ Designated as safety issue: Yes ]
    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.

  • Change in Quantitative Immunoglobulin From Baseline During Short-term Period [ Time Frame: Day 365 ] [ Designated as safety issue: Yes ]

    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


  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in SLICC/ACR Damage Index [ Time Frame: Day 365 to termination of the long-term extension phase ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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

  • Number of Participants Achieving Renal Response [ Time Frame: At Day 365 (end of short-term period) and Day 645 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period [ Time Frame: Month 12 ] [ Designated as safety issue: No ]

    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.



Enrollment: 423
Study Start Date: June 2007
Study Completion Date: August 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430677

  Show 84 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00430677     History of Changes
Other Study ID Numbers: IM101-075
Study First Received: February 1, 2007
Results First Received: February 13, 2012
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glomerulonephritis
Lupus Erythematosus, Systemic
Lupus Nephritis
Nephritis
Kidney Diseases
Urologic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Mycophenolate mofetil
Abatacept
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics

ClinicalTrials.gov processed this record on July 22, 2014