Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study to Evaluate Efficacy and Safety of Treatment With CNTO 136 Administered Intravenously in Subjects With Active Lupus Nephritis
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of CNTO 136 administered intravenously in patients with active, International Society of Nephrology/Renal Pathology Society Class III and IV Lupus Nephritis (LN).


Options:
A: Inclusion Criteria:

* age 16 years of above at the time of screening
* ability and willingness to provide written informed consent (or to obtain consent from parent guardian where applicable) and to comply with the schedule of protocol requirements
* Diagnosis of SLE according to ACR criteria. At least 4 criteria must have been present for the diagnosis of SLE. The 4 criteria do not have to be present at the time of screening
* Active lupus nephritis defined as follows: Biopsy proven (within 16 weeks prior to screening) ISN Class III or IV (A or A/C) not include III(C) IV(C) and VI (\>90% chronic irreversible scarring)
* Relapse or resistant to (3 consecutive doses) IVCY
* Resistant lupus or Relapse lupus nephritis defined as follows:

  * Increase in serum creatinine \>/= 0.3 mg/dl or
  * Increase in proteinuria \> 1.5 g/day (which must have improved by ≥ 50% in the preceding 3 months)
* Life-time cumulative dose of IVCY \> 6 grams
* Female patients of childbearing potential must have a negative serum pregnancy

Exclusion Criteria:

Relates to SLE

* Diagnosis of rapid progressive glomerulonephritis (RPGN): doubling serum creatinine and/or crescentic glomeruli ≥ 30%
* Severe renal impairment as defined by calculated creatinine clearance or MDRD-GFR \< 30 ml/min(except creatinine clearance or MDRD-GFR \> 50 ml/min in the 12 weeks prior to screening)
* History of serious disease or complication in any organ system that not appropriate to treatment immunosuppressive drug groups.
* Severe extra-renal organ involvement

Related to Treatment

* Previous of any Mycophenolate groups in the 6 months prior to screening
* Treatment with any investigational drugs in the 3 months prior to screening

Related to General Health

* Pregnancy or breast feeding mothers.
* Concomitant condition which has required treatment moderate to high dose steroid in the 12 weeks prior to screening.
* Evidence of significant uncontrolled concomitant disease in any organ system not related to SLE.
* History of cancer, including solid tumors, hematological malignancies and carcinoma.
* Evidence of current abuse of drugs or alcohol.

Related to Laboratory Findings

* Neutrophile \< 1,500/mm3, Hb \< 7g/L, Platelet \< 50,000/mm3 (except active SLE)
* Positive HBsAg or anti-HCV or anti-HIV.
B: Inclusion Criteria:

1. A diagnosis of SLE according to the American College of Rheumatology (ACR) criteria
2. Age \>16 years
3. Proteinuria ≥500 mg in 24 hours/ urine routine microscopy showing active cellular casts/sediments.
4. Biopsy-proven proliferative lupus glomerulonephritis of class III, IV according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria.

Exclusion Criteria:

1. Patients ever treated previously with intravenous or oral cyclophosphamide or received steroids \>15mg/day in the last 3 months.
2. Patients with renal thrombotic microangiopathy, preexisting chronic renal failure, pregnancy, previous malignancy (except skin and cervical intraepithelial neoplasia), diabetes mellitus or coronary heart disease.
3. Patients with previously documented severe toxicity to immunosuppressive drugs.
4. Patients with acute/chronic infections.
5. Pregnancy
C: Inclusion Criteria:

1. Patients who fulfill at least 4 of the ACR criteria for SLE
2. Age \>= 18 years
3. Biopsy proven active lupus glomerulonephritis (ISN/RPS class III/IV/V)
4. Serum creatinine \< 200 umol/L at the time of randomization

Exclusion Criteria:

1. Patients who refuse to be randomized for treatment
2. Patients who prefer treatment with conventional agents such as oral or intravenous CYC for various reasons
3. Serum creatinine \>= 200 umol/L at the time of randomization
4. Patients without renal biopsy or those who have lupus nephritis ISN/RPS class I,II,VI
5. Patients who are pregnant or plan for pregnancy within 12 months after randomization
D: Inclusion Criteria:

* Diagnosis of Systemic lupus erythematosus (SLE), and biopsy-proven International Society of Nephrology/Renal Pathology Society Class III or IV lupus glomerulonephritis within approximately 14 months prior to randomization
* Persistently active nephritis defined as, proteinuria greater than 0.5g/day as determined by measurement of total urine protein less than 0.5 g/24- hours or a urine Protein/Creatinine (P/C) ratio greater than 0.5 (mg/mg) in a timed collection of 12 or more hours, for 2 months or more prior to the first administration of study medication and observed during at least 2 visits conducted 1 week apart during the screening period
* Active Class III or Class IV lupus nephritis determined by recent biopsy within approximately 6 months prior to screening or at least 1 of the following 3 criteria: hematuria (blood in urine), anti-DNA positivity, or low C3 or C4 complement levels
* Stable immunosuppression for at least 9 weeks prior to the first administration of study medication consisting of MMF 1-3 g/day (or equivalent dose of MPA) with/without corticosteroids up to prednisone equivalent of 20 mg/day, or azathioprine 1-3 mg/kg/day with/without corticosteroids up to prednisone equivalent of 20 mg/day
* Stable dose of angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) for at least 9 weeks prior to the first administration of study medication
* If using oral corticosteroids, must be on a stable dose equivalent to 20 mg/day or less of prednisone for at least 9 weeks prior to the first administration of study medication

Exclusion Criteria:

* Cyclophosphamide use within 3 months of randomization
* B-cell depletion therapy within 6 months of screening, or evidence of persistent B-cell depletion at the time of screening
* Greater than 50 percent glomerular sclerosis on renal biopsy
* Serum creatinine \> 2.5 mg/dL (SI: \> 177 µmol/L)
* White blood cell count \< 3.5 x 10\^3 cells/µL (SI: \< 3.5 x 10\^9 cells/L) or neutrophils \< 1.96 x 10\^3 cells/µL (SI: \< 1.96 x 10\^9 cells/L)
* Platelets \< 140 x 103 cells/ µL (SI: \< 140 x 10\^9 cells/L)

Answer: D