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

Phase 3
Completed
Conditions
Nephrotic Syndrome
Interventions
Registration Number
NCT02257697
Lead Sponsor
Asahi Kasei Pharma Corporation
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
239
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cyclophosphamide (CTX)Cyclophosphamide (CTX)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.
Mizoribine (MZR)Mizoribine (MZR)Oral administration, daily dose of 150mg (50mg/tablet, t.i.d) All study subjects will receive standard steroid therapies during the study.
Primary Outcome Measures
NameTimeMethod
Total Remission rate52 weeks
Secondary Outcome Measures
NameTimeMethod
Complete Remission rate52 weeks
Partial Remission rate52 weeks
Changes of Overall Remission rate8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Changes of Complete Remission rate8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Changes of Partial Remission rate8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Treatment failure rate52 weeks
Changes and percentage change of 24 hours urine protein and serum albumin from the baseline8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Changes of and percentage change of SCr, eGFR and BUN from the baseline8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Progression to End-Stage Renal Disease or Doubling of SCr through the study52 weeks

Trial Locations

Locations (28)

The First Affiliated Hospital of Guangxi Medical University

🇨🇳

Nanning, Guangxi, China

Wuxi People's Hospital

🇨🇳

Wuxi, Jiangsu, China

Shandong Provincial Hospital

🇨🇳

Jinan, Shandong, China

Fuzhou General Hospital of Nanjing Military Region

🇨🇳

Fuzhou, Fujian, China

The First Affiliated Hospital, Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

Zhongshan Hospital Fudan University

🇨🇳

Shanghai, Shanghai, China

The first Affiliated Hospital of Fujian Medical University

🇨🇳

Fuzhou, Fujian, China

Affiliated Hospital of Guilin Medical University

🇨🇳

Guilin, Guangxi, China

China-Japan Friendship Hospital

🇨🇳

Beijing, Beijing, China

The Third Affiliated Hospital of the Third Military Medical University (Daping Hospital)

🇨🇳

Chongqing, Chongqing, China

The First Affiliated Hospital of Nanchang University

🇨🇳

Nanchang, Jiangxi, China

The First Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

The Second Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

The First Affiliated Hospital of Dalian Medical University

🇨🇳

Dalian, Liaoning, China

The General Hospital of Jinan Military Region

🇨🇳

Jinan, Shandong, China

Renji Hospital Shanghai Jiaotong University School of Medical

🇨🇳

Shanghai, Shanghai, China

Xinhua Hospital Shanghai Jiaotong University School of Medical

🇨🇳

Shanghai, Shanghai, China

The Second Hospital of Shanxi Medical University

🇨🇳

Taiyuan, Shanxi, China

West China Hospital of Sichuan University

🇨🇳

Chengdu, Sichuan, China

The First Affiliated Hospital of Xi'an Jiaotong University

🇨🇳

Xian, Shanxi, China

Kuming General Hospital of Chengdu Military Region

🇨🇳

Kunming, Yunnan, China

Beijing Friendship Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

Beijing Tongren Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

Chinese PLA General Hospital

🇨🇳

Beijing, Beijing, China

The Third Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

The General Hospital of Shenyang Military Region

🇨🇳

Shenyang, Liaoning, China

The Affilited Hospital of Qingdao University

🇨🇳

Qingdao, Shandong, China

The First Affiliated Hospital of College of Medicine, Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

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