RING - Rituximab for Lupus Nephritis With Remission as a Goal

• Status: Unknown status
• Trial end date: 2016-11-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Frédéric A. Houssiau, MD, PhD
• Treatments: Rituximab

Criteria

Inclusion Criteria:

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 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) ;

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).

Exclusion Criteria:

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.