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

Nephrotic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02257697
• Other study ID #: HE-69-C-Ne-302
• Status: Completed
• Phase: Phase 3
• Start date: November 2014
• Est. completion date: November 2018

Study information

• Verified date: January 2019
• Source: Asahi Kasei Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 239
• Est. completion date: November 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Mizoribine (MZR)

• Cyclophosphamide (CTX)

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tongren Hospital, Capital Medical University	Beijing	Beijing
China	China-Japan Friendship Hospital	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	The Second Hospital of Jilin University	Changchun	Jilin
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	The Third Affiliated Hospital of the Third Military Medical University (Daping Hospital)	Chongqing	Chongqing
China	The First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Fuzhou General Hospital of Nanjing Military Region	Fuzhou	Fujian
China	The first Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Affiliated Hospital of Guilin Medical University	Guilin	Guangxi
China	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Shandong Provincial Hospital	Jinan	Shandong
China	The General Hospital of Jinan Military Region	Jinan	Shandong
China	Kuming General Hospital of Chengdu Military Region	Kunming	Yunnan
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The Affilited Hospital of Qingdao University	Qingdao	Shandong
China	Renji Hospital Shanghai Jiaotong University School of Medical	Shanghai	Shanghai
China	Xinhua Hospital Shanghai Jiaotong University School of Medical	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	The General Hospital of Shenyang Military Region	Shenyang	Liaoning
China	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xian	Shanxi

Sponsors (1)

Lead Sponsor	Collaborator
Asahi Kasei Pharma Corporation

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Remission rate		52 weeks
Secondary	Complete Remission rate		52 weeks
Secondary	Partial Remission rate		52 weeks
Secondary	Changes of Overall Remission rate		8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Secondary	Changes of Complete Remission rate		8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Secondary	Changes of Partial Remission rate		8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Secondary	Treatment failure rate		52 weeks
Secondary	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
Secondary	Changes of and percentage change of SCr, eGFR and BUN from the baseline		8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
Secondary	Progression to End-Stage Renal Disease or Doubling of SCr through the study		52 weeks