Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis
Brief Summary: This was a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab in combination with mycophenolate mofetil (MMF) compared with placebo in combination with MMF in subjects diagnosed with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis.


Options:
A: Inclusion Criteria:

1. Female patients with a diagnosis of systemic lupus erythematosus (SLE) according to the criteria of American Rheumatic Association, 1982, aged between 12-50 years, with score of SLE-DAI (Disease Active Index) of more than 12 (not including class V LN).
2. Patients diagnosed according to ISN/RPS 2003 classification criteria: class Ⅲ, Ⅳ, Ⅳ + Ⅴ, Ⅲ + Ⅴ LN by renal biopsy within 3 months, CI\< 4，Scr\< 3 mg/dl.
3. Patients with a proteinuria ≥ 1.5 g/24h, or active urine sediment.
4. Patients who signed written informed consent forms (patients less than 18 years old with their parents/legal representative' signatures), and have given their consent to follow all study procedures and follow-ups.

Exclusion Criteria:

1. Patients who have received treatment of cytotoxic drugs such as cyclophosphamide (CTX), cyclosporine A for more than 1 week within three months.
2. Patients with serum creatinine ≥ 3 mg/dl（265 μmol/L).
3. Patients with severe infection or central nervous system symptoms.
4. Patients who have impaired liver function, with ALT/GPT or AST/GOT twice more than the normal upper limit or who have active hepatitis.
5. Patients who have abnormal blood glucose, with a fasting blood glucose \> 6.2 mmol/L or post meal blood glucose \> 11.2 mmol/L.
6. Patients who are pregnant or lactating.
7. Patients who are known to be allergic to a macrolide.
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:

* Diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria.
* Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis (LN), with either active or active/chronic disease.
* Proteinuria.
* 16-75 years of age.

Exclusion Criteria:

* Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE.
* Unstable subjects with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions.
* Lack of peripheral venous access.
* Pregnancy or lactation.
* History of severe allergic or anaphylactic reactions to monoclonal antibodies.
* Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude subject participation.
* Concomitant chronic conditions, excluding SLE (eg, asthma, Crohn's disease) that require oral or systemic corticosteroid use in the 52 weeks prior to screening.
* History of renal transplant.
* Known human immunodeficiency virus (HIV) infection.
* Known active infection of any kind (but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with intravenous anti-infectives within 4 weeks of randomization or oral anti-infectives within 2 weeks of randomization.
* History of deep space infection within 1 year of screening.
* History of serious recurrent or chronic infection.
* History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinomas of the skin that have been treated or excised and have resolved).
* Currently active alcohol or drug abuse or history of alcohol or drug abuse within 52 weeks prior to screening.
* Major surgery requiring hospitalization within 4 weeks of screening (excluding diagnostic surgery).
* Treatment with cyclophosphamide or calcineurin inhibitors within the 90 days prior to screening.
* Use of mycophenolate mofetil (MMF) at a dose of \> 2 grams daily for longer than the 90 days prior to screening.
* Intolerance or history of allergic reaction to MMF.
* Intolerance or history of allergic reaction to both angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers.
* Use of oral prednisone (or corticosteroid equivalent) at a dose of \> 20 mg/day for longer than the 14 days prior to screening.
* Previous treatment with CAMPATH-1H (alemtuzumab).
* Previous treatment with a B-cell targeted therapy.
* Treatment with any investigational agent (including biologic agents approved for other indications) within 28 days of the start of the screening period or 5 half-lives of the investigational drug (whichever is longer).
* Receipt of a live vaccine within the 28 days prior to screening.
* Intolerance or contraindication to oral or IV corticosteroids.
* Current therapy with a nonsteroidal anti-inflammatory agent.
* Positive hepatitis B sAg or hepatitis C serology.
D: 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.

Answer: C