A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome

Study Overview
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Brief Summary
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To demonstrate that the treatment effect in refractory nephrotic syndrome 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 Refractory Nephrotic Syndrome

Conditions
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Nephrotic Syndrome

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: Patients who have medical history with clear documentation of diagnosis of nephrotic syndrome Patient who received renal biopsy within 1 year prior to screening and confirmed the pathologic classification: Minimal Change Disease (MCD), IgA nephropathy, Mesangioproliferative Glomerulonephritis (MsPGN), Membranous Nephropathy (MN), Focal Segmental Glomerulosclerosis (FSGS) Patient with the above different pathologic classification who received adequate hormone therapy more than 8 weeks (including FSGS more than 12 weeks)prior to screening and have 24hr-urine protein≥2.0g/day at screening Adequate hormone dose is defined as prednisone (prednisolone) equivalent dose of 0.8 to 1.0 mg/kg/day (inclusive) 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: Other primary nephrotic syndrome, e.g. membrano-proliferative glomerulonephritis (MPGN) Secondary nephrotic syndrome (e.g. diabetic nephropathy, anaphylactic purpura nephritis, lupus nephritis, type B hepatitis-related nephritis, renal amyloidosis) 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 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 | 
| Progression to End-Stage Renal Disease or Doubling of SCr through the study |  | 52 weeks |