A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Lupus Nephritis

Study Overview
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Brief Summary
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To demonstrate that the treatment effect in lupus nephritis of MZR is non-inferior to that of standard therapy CTX through analyzing overall remission rate after treatment.

Official Title
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A Multi-center, Randomized, Controlled, Open-label Clinical Study to Evaluate the Efficacy and Safety of Mizoribine in Comparison With Cyclophosphamide in the Treatment of Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Mizoribine (MZR)
* Drug: Cyclophosphamide (CTX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has been diagnosed with SLE according to American College of Rheumatology (ACR) criteria in 1997; Patient who has had a kidney biopsy within 365 days prior to screening which was confirmed as class III, III+V, IV, IV+V, or V according to the pathologic classification of International Society of Nephrology/Renal Pathology Society (ISN/RPS) in 2003; Patient with 24hr-urine protein ≥ 1.0g; SLE-DAI > 8 ; Male or female patient between 18 and 70 years (inclusive) at informed consent obtained date; Patient with body weight between 40kg and 80kg (inclusive) at screening; Patients who sign the informed consent form; Exclusion Criteria: Patient who had history of allergy to any investigational product (MZR, CTX) or hormone; Patient who had received accumulated dosage of CTX >3g within one year prior to screening. Patient who had received immunosuppressant or Chinese traditional medicine with immunosuppressive effect within 30 days prior to screening; Patient who had received prednisone>1.0mg/kg/day or equivalent dose of other oral glucocorticoid therapies within 30 days prior to screening; Patient who received other investigational drugs within 30 days prior to screening; Patient who have received plasma exchange therapy or immunoadsorption therapy within 30 days prior to screening; Patient who require pentostatin or live vaccine (not including flu vaccine); Patient who is undergoing renal replacement therapy; Patient who received kidney transplantation; Patient with malignancy; Patient with severe hypertension (SBP > 160mmHg or DBP > 100mmHg) which has not been effectively controlled; Patient with white blood cell count <3×109/L /L(=3.0 GI/L); Patient with SCr > 176.8μmol/L; Patient who has a value that is > 3 times of the upper limit of normal range for AST or ALT; Patient with hepatitis B, hepatitis C or HIV infection; Patient with other serious infections; Patient who is unsuitable for participating in this study in the opinion of investigators ( e.g. uncontrolled diabetes, central nervous system lupus , lupus encephalopathy, active psychosis,osteonecrosis of the femoral head, fulminant hepatitis, peptic ulcer, etc.); Female patient who is pregnant, currently breast feeding or willing to become pregnant; Patient with any other diseases that would affect the evaluation of efficacy or safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mizoribine (MZR)<br>Oral administration, daily dose of 150mg (50mg/tablet, t.i.d) All study subjects will receive standard steroid therapies during the study. | Drug: Mizoribine (MZR)<br> <br> * Other names: HE-69;|
| Active Comparator: Cyclophosphamide (CTX)<br>Intravenous injection with between 0.5 to 1.0 g/m2 body surface area each time (the maximum dose is 1.0 g/day each time). All study subjects will receive standard steroid therapies during the study. | Drug: Cyclophosphamide (CTX)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Remission rate |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission rate |  | 52 weeks | 
| Partial Remission rate |  | 52 weeks | 
| Changes of Overall Remission rate |  | 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks | 
| Changes of Complete Remission rate |  | 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks | 
| Changes of partial remission rate |  | 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks | 
| Treatment failure rate |  | 52 weeks | 
| Changes and percentage change of 24 hours urine protein and serum albumin from the baseline |  | 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks | 
| Changes of and percentage change of SCr, eGFR and BUN from the baseline |  | 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks | 
| Changes of immunological test (C3, Anti-DNA antibody, ANA, Anti-Sm antibody and Anti-phospholipid antibody) from baseline |  | 20 weeks and 52 weeks | 
| Changes of SLE-DAI score from baseline |  | 20 weeks and 52 weeks | 
| Progression to End-Stage Renal Disease or Doubling of SCr through the study. |  | 52 weeks |