RING - Rituximab for Lupus Nephritis With Remission as a Goal, an Investigator-initiated Randomized International Open Multicentric Study
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 194
- 试验地点
- 1
- 主要终点
- The primary endpoint is the percentage of patients achieving renal complete response (CR) at w104.
研究概览
简要总结
OBJECTIVE To test whether Rituximab (RTX) is efficacious to achieve complete renal response (CR) in Lupus Nephritis (LN) patients with persistent proteinuria (≥1g/d) despite at least 6 months of standard of care (SOC).
STUDY DESIGN Investigator-initiated randomized international open multicentric 104-week study.
详细描述
After screening (week -8), patients enter in a run-in period of 6 weeks during which treatment is unchanged. At week -2, if persistent proteinuria is confirmed (uP/C ratio ≥1 expressed in mg/mg), patients will be randomized in a 1/1 ratio to 1 of 2 treatment groups as follows :
RTX group Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.Control group Subjects will not receive RTX infusions. In both arms, azathioprine (AZA) or mycophenolate mofetil (MMF) will be continued. If prescribed, prednisolone dose should not be > 10 mg/day.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All the following inclusion criteria are to be met :
- •SLE, according to ACR and/or SLICC (Arthritis Rheum 2012; May 2; doi: 10.1002/art.34473) criteria ;
- •Age ≥15y (except if local ethics committee imposes ≥18y) ;
- •ISN/RPS 2003 Class III (A or A/C), IV (A or A/C ; S or G) or V lupus GN confirmed on renal biopsy performed within 24 months before screening ;
- •Having received one out of four following immunosuppressive regimens:
- •i): Euro-Lupus (EL) intravenous (IV) cyclophosphamide (CY) (6x 500 mg q2w) followed by AZA/MMF for 3 months ; ii): NIH IVCY for 6M (6 monthly pulses) followed by AZA/MMF for 3 months ; iii): MMF for at least 6 months at a dose of 2g/day (or the maximal tolerated dose; iv): AZA for at least 6 months at a dose of 2 mg/kg/day (or the maximal toerated dose).
- •All patients should be on AZA or MMF at screening. In all regimens, MMF can be replaced by enteric-coated mycophenolic acid (eMPA) ;
- •If on GC, being on maximum 10 mg equivalent prednisolone/d at screening (for at least 2 weeks) ;
- •uP/C ratio ≥1 (expressed in mg/mg) measured in a 24-h urine collection, confirmed at randomization (w-2) ;
- •Contraception (any type ; sexual abstinence is an alternative to contraception in paediatric patients) ;
- •Signed informed consent (drafted according to local practice and approved by the local ethics committee).
排除标准
- •Any of the following :
- •Recent or ongoing renal flare defined as either i) : fall in estimated glomerular filtration rate (eGFR ; MDRD) ≥25% within 3 month prior to screening or between screening and randomization ; or ii) : increase in urine protein by ≥100% to >3.5g/d compared to previous assessment ;
- •24-h proteinuria decline >50% over previous 6 months ;
- •Treatment with ≥10 mg equivalent prednisolone/d in the last 2 weeks before screening ;
- •Pregnancy or breast-feeding ;
- •Anticipated non-compliance with the protocol ;
- •History of malignancy (except non-melanoma skin and cervical intraepithelial cancer) ;
- •Previous treatment with RTX (whenever) and previous treatment with another biologic agent within the last 6 months ;
- •HIV infection ;
- •Active HBV/HCV/TB infection ;
- •Severe liver, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, haematologic or psychiatric disturbances, that would contraindicate inclusion in the protocol, as judged by the clinician.
研究组 & 干预措施
RTX group
Subjects will receive a RTX infusion (1g) at w0, w2, w24, w48 and w72.
干预措施: RTX infusions (Drug)
Control group
Subjects will not receive RTX infusions and will be followed in standard of care
干预措施: Standard of Care (Other)
结局指标
主要结局
The primary endpoint is the percentage of patients achieving renal complete response (CR) at w104.
时间窗: 104 weeks
CR is defined as : * uP/C ratio ≤0.5 (expressed in mg/mg) measured in a 24-h urine collection; and * eGFR \>=60ml/min or, if \<60ml/min at screening, not fallen by \>20% compared to screening; and * no increase of glucocorticoïds (GC) throughout the study (except for two limited courses as per protocol; vide infra); and * no introduction of another immunosuppressant.
次要结局
未报告次要终点
研究者
Frédéric A. Houssiau, MD, PhD
Professeur Ordinaire, Chef de Service Clinique
Université Catholique de Louvain