Clinical trial NCT02256150: A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Lupus Nephritis
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 Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lupus Nephritis
Lead sponsor: Asahi Kasei Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2014-10-03
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Total Remission rate
timeFrame: 52 weeks
Secondary outcomes:
measure: Complete Remission rate
timeFrame: 52 weeks
measure: Partial Remission rate
timeFrame: 52 weeks
measure: Changes of Overall Remission rate
timeFrame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of Complete Remission rate
timeFrame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of partial remission rate
timeFrame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Treatment failure rate
timeFrame: 52 weeks
measure: Changes and percentage change of 24 hours urine protein and serum albumin from the baseline
timeFrame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of and percentage change of SCr, eGFR and BUN from the baseline
timeFrame: 8 weeks, 20 weeks, 32 weeks, 44 weeks and 52 weeks
measure: Changes of immunological test (C3, Anti-DNA antibody, ANA, Anti-Sm antibody and Anti-phospholipid antibody) from baseline
timeFrame: 20 weeks and 52 weeks
measure: Changes of SLE-DAI score from baseline
timeFrame: 20 weeks and 52 weeks
measure: Progression to End-Stage Renal Disease or Doubling of SCr through the study.
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The Third Affiliated Hospital of the Third Military Medical University (Daping Hospital)
state: Chongqing
city: Fuzhou
country: China
facility: The first Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military Region
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jinan
country: China
facility: The General Hospital of Jinan Military Region
state: Shandong
city: Qingdao
country: China
facility: The Affilited Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medical
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Xian
country: China
facility: The First Affiliated Hospital of the Fourth Military Medical University (Xijing Hospital)
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: Kuming General Hospital of Chengdu Military Region
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Asahi Kasei Pharma Corporation
name: Asahi Kasei Pharma Corporation
role: STUDY_CHAIR
References: