Idiopathic Membranous Nephropathy
Conditions
Keywords
Rituximab, cyclosporine, idiopathic membranous nephropathy
Brief summary
The primary objective of this study is to determine whether or not cyclosporine (CsA) combined with RTX is more effective than RTX alone in the treatment of idiopathic membranous nephropathy (iMN).
Detailed description
To date, the first-line immunosuppressive therapy of iMN includes corticosteroids combined with cyclophosphamide or Rituximab (RTX) which has been used more and more widely due to superior safety profiles. But the long term remission rate of RTX monotherapy is only 60% and it takes effect relatively slowly. 2 pilot studies reported that the combination therapy of cyclosporine (CsA) and RTX had better efficacy for inducing remission for iMN, with the long term remission rate up to 85%. CsA and RTX may have synergistic effect in the treatment of iMN because they have different time of action and different effects on the immune system and podocytes. Based on the previous rationale, the investigators designed this trial to determine whether combination of CsA and RTX is more effective than RTX alone in the treatment of iMN.
Interventions
DRUGRituximab
Rituximab 1000mg, I.V. on Days 1 and 181, and will be retreated or not at Days 15 and 195 according to the CD19+ B cell count.
DRUGcyclosporine
cyclosporine (CsA) will be started at a dose of 3mg/kg/d and adjusted according to the blood levels of the CsA. CsA will be tapered after 6 months and discontinued over a three month period.
Sponsors
Beijing Tongren Hospital
Chinese Academy of Medical Sciences, Fuwai Hospital
The Luhe Teaching Hospital of the Capital Medical University
The Seventh Affiliated Hospital of Sun Yat-sen University
First Affiliated Hospital of Xinjiang Medical University
Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* idiopathic MN with or without diagnostic biopsy * Female, must be post-menopausal, sterile or have effective method of contraception * must be off steroid or mycophenolate mofetil for \>1 month and alkylating agents for \> 6 months * Angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for ≥3 months prior to randomization with controlled blood pressure or if patients is intolerant to ACEI/ARB * proteinuria ≥4g/24h using the average from two 24-hour urine samples collected within 2 weeks of each other, and decreased ≤50% from baseline. * estimated glomerular filtration rate (eGFR) ≥40ml/min/1.73m2
Exclusion criteria
* presence of active infection or a secondary cause of MN * diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. * pregnancy or breast feeding * history of resistance to CsA or other calcineurin inhibitors(CNI), RTX or alkylating agents. * Patients who previously achieved remission after treatment of CNI, RTX or alkylating agents but relapsed off CNI after 3 months, or relapsed off RTX or alkylating agents after 6 months, are eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| complete remission (CR) or partial remission (PR) at 24 month | 24 months after randomization | complete or partial remission at 24 month. complete remission is defined as urine protein≤0.5g/24h and serum albumin≥3.5g/dl. Partial remission is defined as reduction in baseline urine protein ≥50% plus urine protein≤3.5g/24h but \>0.5g/24h |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| complete remission (CR) on 6, 12, 18, 24 month | 6, 12, 18, 24 months after randomization | complete remission on month 6, 12, 18 and 24 |
| Time to complete remission (CR) or partial remission (PR) | from date of randomization until the date of first remission, assessed up to 24 months | Time to complete or partial remission |
| Change of estimated glomerular filtration rate (eGFR) | 24 months | Change of eGFR from baseline to 24 months |
| Serum creatinine increase≥50 percent from baseline | 24 months | proportion of patients with increase of serum creatinine ≥50 percent from baseline |
| complete remission (CR) or partial remission (PR) on 6 month, 12 month, 18 month | 6, 12, 18 months after randomization | complete or partial remission on month 6, 12 and 18 |
| Anti-PLA2R titer | baseline and 3, 6, 9, 12, 18, 24 months | Auto-antibodies to the M-type phospholipase A2 receptor(PLA2R) |
| The number of CD19+B cells | baseline and 3, 6, 9, 12, 18, 24 months | CD19+ B cells |
| Quality of life measured by kidney disease and quality of life (KDQOL-36) | baseline, 12 and 24 month | KDQOL-36 includes 36 questions which are scored positively (higher score indicating better quality of life) on a 0-100 scale using developer-recommended scoring. |
| Adverse events | through study completion until 24 months | adverse events |
| Proportion of patients with relapse | 12，18，24 months | Rate of relapse. Relapse is defined as development of nephrotic range proportion of patients with relapse. Relapse is defined as development of proteinuria\>3.5g/24h following CR or PR. |
Countries
China
Outcome results
None listed