Lupus Nephritis MedDRA version: 18.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
Cliniques Universitaires Saint Luc, Université catholique de Louvain
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria (at screening) All the following inclusion criteria are to be met : 1. SLE, according to ACR and/or SLICC (Arthritis Rheum 2012; May 2; doi: 10.1002/art.34473) criteria ; 2. Age =15y (except if local ethics committee imposes =18y) ; 3. 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 ; 4. 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; iv): AZA for at least 6 months All patients should be on AZA or MMF at screening. In all regimens, MMF can be replaced by enteric-coated mycophenolic acid (eMPA) ; 5. If on GC, being on maximum 10 mg equivalent prednisolone/d at screening (for at least 2 weeks) ; 6. uP/C ratio =1 (expressed in mg/mg) measured in a 24-h urine collection, confirmed at randomization (w-2) ; 7. Contraception (any type ; sexual abstinence is an alternative to contraception in paediatric patients) ; 8. Signed informed consent (drafted according to local practice and approved by the local ethics committee). Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 179 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Exclusion criteria (at screening, except exclusion criteria 1 at randomization). Any of the following : 1. 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 ; 2. 24-h proteinuria decline >50% over previous 6 months ; 3. Treatment with =10 mg equivalent prednisolone/d in the last 2 weeks before screening ; 4. Pregnancy or breast-feeding ; 5. Anticipated non-compliance with the protocol ; 6. History of malignancy (except non-melanoma skin and cervical intraepithelial cancer) ; 7. Previous treatment with RTX (whenever) and previous treatment with another biologic agent within the last 6 months ; 8. HIV infection ; 9. Active HBV/HCV/TB infection ; 10. Severe liver, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, haematologic or psychiatric disturbances, that would contraindicate inclusion in the protocol, as judged by the clinician.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: OBJECTIVE: To test whether RTX is efficacious to achieve complete renal response (CR) in LN patients with persistent proteinuria (=1g/d) despite at least 6 months of standard of care (SOC). ;Secondary Objective: 1.Number of deaths ;2.Number of side-effects ;3.Number of SAEs ;4.Number of infections requiring antibiotics ;5.Number of discontinuations for toxicity ;6.Number of patients reaching ESRD ;7.Number of patients with sustained doubling of serum creatinine or sustained fall >25% in eGFR ;8.Number of renal flares, nephritic or proteinuric according to Moroni et al. (Kidney Int 1996; 50 : 2047) ;9.Time to CR ;10.Time to CR for patients achieving CR at w104 ;11.Number of patients achieving a proteinuria = 60ml/min or, if 20% compared to screening; and - no increase of GC throughout the study (except for two limited courses as per protocol; vide infra); and - no introduction of another immunosuppressant.;Timepoint(s) of evaluation of this end point: Week104 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints (evaluated at w104) are: 1. Number of deaths ; 2. Number of side-effects ; 3. Number of SAEs ; 4. Number of infections requiring antibiotics ; 5. Number of drops for toxicity ; 6. Number of patients reaching ESRD ; 7. Number of patients with sustained doubling of serum creatinine or sustained fall >25% in eGFR ; 8. Number of renal flares, nephritic or proteinuric according to Moroni et al. (Kidney Int 1996; 50 : 2047) ; 9. Time to CR ; 10. Time to CR for patients achieving CR at w104 ; 11. Number of patients achieving a proteinuria <0.2g/d ; 12. Number of patients achieving the ACR response criteria for renal disease in SLE (Arthritis Rheum 2006; 54 : 421) ; 13. Number of mild/moderate and severe flares according the to SELENASLEDAI flare index ; 14. Number of patients with normalized serum complement levels (centrally measured on stored samples); 15. Number of patients with decrease in serum anti-DNA Ab titers by 2 compared to baseline (centrally measured on stored samples); 16. Grams equivalent prednisolone exposure. Analyses will be performed on the Intent-To-Treat (ITT) population and the;Timepoint(s) of evaluation of this end point: Week104 | — |
Countries
Argentina, Belgium, Brazil, Colombia, Czech Republic, European Union, Morocco, Russian Federation, Spain, Sweden, Switzerland, Turkey
Contacts
Public ContactPôle de pathologies rhumatismales
Cliniques Universitaires Saint Luc, Université catholique de Louvain
Outcome results
None listed