A Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis

A Phase III, Randomized, Open, Parallel-controlled, Multi-center Study to Compare the Efficacy and Safety of Tacrolimus Capsules and Cyclophosphamide Injection in Treatment of Lupus Nephritis

The objective of this study is to evaluate the efficacy and safety of Tacrolimus capsules for induction remission in patients with lupus nephritis, and compare the efficacy and safety with Cyclophosphamide injections.

This is a randomized, open, 1:1 parallel controlled, multi-center, non-inferiority clinical study.

Inclusion Criteria:

• 18.5≤Body Mass Index (BMI) <27;
• Diagnosed as systemic lupus erythematosus (based on American Rheumatism Association Diagnostic Criteria 1997)
• Diagnosed as III, IV, V, III + V, IV + V lupus nephritis (according to the LN classification in International Society of Nephrology and Renal Pathology Society (ISN/RPS) 2003) within 24 weeks before enrollment with renal biopsy;
• 24-hour urine protein ≥ 1.5g, Scr<260umol/L (or 3mg/dL)

Exclusion Criteria:

• Class II or VI lupus nephritis or renal biopsy chronic index (CI) > 3 or with TMA;
• Received immunosuppressants (mycophenolate mofetil (MMF), cyclosporine, methotrexate, mechlorethamine, chlorambucil, tripterygium preparations, leflunomide etc.) treatment with a duration of more than one week within 30 days prior to enrollment;
• Received tacrolimus (except for topical use) or cyclophosphamide treatment within 30 days prior to enrollment;
• Received a course of methylprednisolone (MP) pulse therapy or gamma globulin treatment or plasma exchange within 30 days prior to enrollment;
• Patients with history of allergies to tacrolimus, cyclophosphamide or methylprednisolone;
• Pregnancy, lactation or patient unwilling to take contraceptive measures;
• Patients with estimated maintenance dialysis for more than eight weeks; or dialysis for more than two weeks prior to entering observation;
• Patients received kidney transplantation or plan to have kidney transplantation recently;
• Serum creatinine (Scr) ≥260umol/L (or 3mg/dL) or creatinine clearance rate (Ccr) < 30ml/(min.1.73m2); according to Cockcroft-Gault formula: Ccr (ml/sec) = [(140- age)× Weight (kg)] × K / [72×Scr (umol/L) ×0.6786], Female K = 0.85, Male K = 1.0;
• Patients suffering from liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times the upper limit of normal lab value) or bilirubin more than 3 times the upper limit of normal lab value;
• Patients diagnosed with diabetes;
• History of gastrointestinal bleeding or pancreatitis within 3 months;
• Uncontrollable hyperkalemia after dietary therapy or reduction of potassium treatment (exceed the upper limit of normal lab value);
• Patients suffering from lupus pneumonia or lung injury;
• Patients with anemia (hemoglobin <7g/dl) or bone marrow suppression (WBC <3.0×109/L, and/or neutrophils <1.5×109/L, and/or platelets <50×109/L) not secondary to systemic lupus erythematosus;
• With congenital heart disease, arrhythmia, heart failure or other severe cardiovascular diseases;
• With refractory hypertension (defined as blood pressure still exceeds 180/110 mmHg despite taking three different types of antihypertensive drugs [one of them is diuretic] simultaneously);
• Patients with recurrent tumors within 5 years;
• Severe infection that requires intravenous antibiotics within 2 weeks prior to enrollment;
• Patients with infection of hepatitis B virus or hepatitis C virus; patients with active tuberculosis; patients with severe immunodeficiency diseases (including active cytomegalovirus infection (positive CMV IgM antibody), or human immunodeficiency virus (HIV) infection, etc.);
• Patients with lupus encephalopathy or other life-threatening complication of systemic lupus erythematosus;
• Patients participated in other clinical trials within three months before enrollment