Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Controlled, Phase II Multicenter Trial of CTLA4Ig (Abatacept) Plus Cyclophosphamide vs Cyclophosphamide Alone in the Treatment of Lupus Nephritis
Brief Summary: This study is for individuals with lupus who have developed complications in their kidneys, or lupus nephritis. The study will determine whether adding the experimental medication abatacept to standard cyclophosphamide therapy is more effective in improving lupus nephritis than standard cyclophosphamide therapy by itself.


Options:
A: Inclusion Criteria:

* the diagnosis of systemic lupus erythematosus (by meeting 4 criteria of the American College of Rheumatology)
* renal biopsy documenting lupus nephritis according to the classification of the World Health Organization (WHO) or the updated International Society of Nephrology/Renal Pathology Society (ISN/RPS) as proliferative glomerulonephritis class III (focal) or IV (diffuse)
* clinical activity as defined by presence of at least two of the following:

  * abnormal proteinuria (more than 500mg of protein in in a 24-hour urine specimen)
  * abnormal microscopic hematuria, or
  * C3 hypocomplementemia (the latter two were defined according to the norms in the laboratories of the participating centers)

Exclusion Criteria:

* treatment with cyclophosphamide or cyclosporine A ever before
* treatment with other immunosuppressive drugs (such as azathioprine or mycophenolate mofetil) or high dose glucocorticoids (≥ 80mg of prednisone or methylprednisolone) within the last 3 months
* persistent elevation of serum creatinine (≥140 μmol/l)
* pregnancy or lactation
* bone marrow insufficiency with cytopenias not attributable to SLE, and 8severe coexisting conditions, such as infection, liver disease, active peptic ulcer etc.
B: Inclusion Criteria:

* Diagnosis of systemic lupus erythematosus (SLE) by American College of Rheumatology (ACR) criteria
* Active lupus nephritis (defined by: kidney biopsy documentation within the last 12 months using International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification- proliferative nephritis, active urinary sediment, urine protein-to-creatinine ratio \> 1, low complement C3)
* Positive antinuclear antibody (ANA) test result at time of study entry

Exclusion Criteria:

* End stage renal disease
* Use of cyclophosphamide in the past year
* Neutropenia, thrombocytopenia, moderately severe anemia
* Active infection, including HIV, hepatitis B or C
* History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas
* Pregnant or breastfeeding
C: Inclusion Criteria:

1. Subjects of either sex, 14-65 years of age;
2. Diagnosis of SLE according to the ACR criteria(1997);
3. Kidney biopsy within the 6 months prior to first randomization with a histologic diagnosis (ISN/RPS 2003 classification of LN) class III, IV, V;
4. Class IV LN: proteinuria \>1g/24hr or Scr\>115umol/L;
5. Class III or V LN: proteinuria \>2g/24hr or Scr\>115umol/L;
6. Provision of written informed consent by subject or guardian.

Exclusion Criteria:

1. Inability or unwillingness to provide written informed consent ;
2. Known hypersensitivity or contraindication to tacrolimus, cyclophosphamide , azathioprine, corticosteroids;
3. Usage of immunosuppression therapy (MMF, CTX, CysA, MTX ect) for more than 1 week within 1 month prior to first randomization;
4. Pregnancy, nursing or use of a non-reliable method of contraception;
5. Continuous dialysis starting more than 2 weeks before randomization into the induction phase and/or continuous dialysis with an anticipated duration of more than 8 weeks;
6. Previous kidney transplant or planted transplant;
7. Scr \> 4mg/dl (353umol/L);
8. Active hepatitis, with liver dysfunction;
9. Diagnosed DM;
10. Participation in another clinic trial and/or receipt of investigational drugs within 4 weeks prior to screening .
D: Inclusion Criteria:

* Men and women, between the ages of 18 and 70 years of age;
* Body mass index from 18 to 40 kg/m2 \[Body Weight (kg)/Height2 (m2)\] at screening;
* Diagnosis of SLE at least 6 months before randomization, including a positive antinuclear antibodies (ANA) during screening; if screening ANA is negative, documented historical ANA with a titer of at least 1:80 will be acceptable;
* Any concurrent SLE pharmacologic regimen (including mycophenolate mofetil, azathioprine, leflunomide, methotrexate, and anti-malarials) must be stable for at least 30 days before randomization;
* Prednisone ≤ 20 mg/day (or equivalent) is permitted; one increase or one decrease of ≤ 5 mg/day prednisone equivalent will be allowed within 30 days before randomization;

Additional inclusion criteria for Part B:

- Active SLE with GN with no other apparent cause, defined by the following: Renal biopsy evidence (within 18 months) of nephritis using the WHO or International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification of SLE with GN (Class III or IV); Urine protein/creatinine ratio (UP/Cr) \> 1 or 24 hour urine protein \> 1g after at least 12 weeks of treatment with mycophenolate mofetil (at least 1.5 grams/day) or azathioprine (at least 100 mg orally per day); Superimposed membranous changes are allowed for those with Class III or Class IV SLE with GN;

- Prednisone ≤ 20 mg/day (or equivalent) at the time of randomization.

Exclusion Criteria:

* Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of SLE) that would, by its progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures per the investigator's discretion;
* Creatinine clearance within the screening period of less than 50 mL/min as calculated by the Cockcroft-Gault method
* Signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization, or recent history of repeated infections;
* Underlying condition other than SLE or being on allowed immunosuppressants that predisposes one to infections
* Prior use of the following agents:
* Administration of an investigational biologic agent that primarily targets the immune system
* Administration of cyclosporine, tacrolimus, sirolimus, IV immunoglobulin, and/or plasmapheresis within 3 months of randomization;
* Administration of oral or IV cyclophosphamide (or any other alkylating agent) within 12 months (Part A) or 3 months (Part B) of randomization;
* History of ethanol or drug abuse within the last one year prior to randomization;

Additional exclusion criteria for Part B:

* Rapidly progressive GN (defined as a doubling of serum creatinine within the past 3 months);
* Evidence of significant chronicity, defined as:

\> 50% glomeruli with sclerosis or \> 50% interstitial fibrosis on renal biopsy; or International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 Class III (C), IV-S (C) or IV-G (C).

Answer: B