Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

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• Lupus Erythematosus, Systemic 1,202

Lupus Erythematosus, Systemic

1,202 studies on the registry are indexed under Lupus Erythematosus, Systemic; 399 are open to participants now.

This study's enrollment of 423 is above the median of 50 across 867 interventional studies indexed under Lupus Erythematosus, Systemic.

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.

Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.

Study arms

• Experimental
  Abatacept 30 mg/kg+Corticosteroids+MMF

  Short-term Period

  Drug: Corticosteroids (prednisone or prednisolone) · Drug: Abatacept · Drug: Mycophenolate mofetil (MMF)

• Experimental
  Abatacept 10 mg/kg+Corticosteroids+MMF

  Short-term Period

  Drug: Corticosteroids (prednisone or prednisolone) · Drug: Abatacept · Drug: Mycophenolate mofetil (MMF)

• Experimental
  Placebo+Corticosteroids+MMF

  Short-term Period

  Drug: Corticosteroids (prednisone or prednisolone) · Drug: Mycophenolate mofetil (MMF)

• Experimental
  Abatacept 10mg/kg

  Long-term Extension Period

  Drug: Abatacept

Interventions

• DrugCorticosteroids (prednisone or prednisolone)

  tablets, oral, 0.5-0.8 mg/kg, daily

• DrugAbatacept

  intravenous solution, injectable, 30 mg/kg, every 28 days

  Also known as: Orencia, BMS-188667

• DrugAbatacept

  intravenous solution, injectable, 10 mg/kg, every 28 days

  Also known as: Orencia, BMS-188667

• DrugMycophenolate mofetil (MMF)

  tablets, oral, 1.5 to 2 g, daily

• DrugAbatacept

  intravenous solution, injectable, 10 mg/kg, every 28 days

Primary outcomes

1. 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.

   Time frame: Day 1 (randomization) to 12 months.

Secondary outcomes

1. 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.

   Time frame: Day 1 to 12 months

2. 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.

   Time frame: At Month 12 from Day 1

3. 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.

   Time frame: Day 1 (randomization) to 12 months.

4. 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.

   Time frame: At Month 12 from Day 1

5. 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.

   Time frame: Day 1 (randomization) to 12 Months

6. 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.

   Time frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365

7. 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.

   Time frame: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365

8. 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.

   Time frame: Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)

9. 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.

   Time frame: Month 12

10. 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.

    Time frame: Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)

11. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

12. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

13. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

14. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

15. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

16. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

17. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

18. 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.

    Time frame: Baseline (Day 1), Days 85, 169, 253, and 365

19. 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.

    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.

20. 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.

    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.

21. 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.

    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.

22. 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

    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.

23. 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.

    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.

24. 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).

    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.

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

    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.

    Time frame: Day 169, Day 365

30. 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.

    Time frame: Baseline (Day 1)

31. 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

    Time frame: Day 365

32. 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.

    Time frame: End of short-term period (Day 365) to termination of the long-term extension period

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

    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.

    Time frame: At Day 365 (end of Short-term Period) and Day 645

34. 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.

    Time frame: Day 365 to termination of the long-term extension phase

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

    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.

    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.

36. 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

    Time frame: Day 365 to end of long-term extension period

37. 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.

    Time frame: At Day 365 (end of short-term period) and Day 645

38. 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.

    Time frame: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period

39. 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.

    Time frame: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period

40. 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.

    Time frame: From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period

Other outcomes

1. Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period

   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.

   Time frame: Month 12

Baseline characteristics

Publications

• Wolf BJ, Spainhour JC, Arthur JM, Janech MG, Petri M, Oates JC. Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. Arthritis Rheumatol. 2016 Aug;68(8):1955-63. doi: 10.1002/art.39623. PubMed 26867033 ↗
• Furie R, Nicholls K, Cheng TT, Houssiau F, Burgos-Vargas R, Chen SL, Hillson JL, Meadows-Shropshire S, Kinaszczuk M, Merrill JT. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol. 2014 Feb;66(2):379-89. doi: 10.1002/art.38260. PubMed 24504810 ↗
• Wofsy D, Hillson JL, Diamond B. Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials. Arthritis Rheum. 2013 Jun;65(6):1586-91. doi: 10.1002/art.37940. PubMed 23529285 ↗
• Wofsy D, Hillson JL, Diamond B. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum. 2012 Nov;64(11):3660-5. doi: 10.1002/art.34624. PubMed 22806274 ↗

Related links

• Investigator Inquiry form ↗