Trial of Rituximab and Mycophenolate Mofetil Without Oral Steroids for Lupus Nephritis

TRIAL SUMMARY TITLE RITUXILUP - An open label randomised multicentre controlled trial of RITUXImab and mycophenolate mofetil (MMF) without oral steroids for the treatment of LUPus nephritis OBJECTIVES 1. Is the combination of Rituximab, Methyl prednisolone and MMF as effective in treating lupus nephritis as Methyl prednisolone, oral steroids and MMF? 2. Does the omission of oral steroids increase the safety of the treatment regimen? DESIGN This is a 1:1 randomised, international open label, controlled phase III multicentre trial SAMPLE SIZE A total of 252 patients: 126 patients in each arm (As of April 2017 decided 25 patients will be maximum recruited following decision to close the study early) ELIGIBILITY Children (12 years and above) and adults with lupus nephritis ISN/RPS Class III A or A/C, Class IV-G A or A/C, Class IV-S A or A/C, and/or Class V with a urine protein/creatinine ratio (PCR) ≥ 100mg/mmol. TREATMENT 1. Experimental group - Rituximab, IV methyl prednisolone and mycophenolate mofetil 2. Control group - oral prednisolone, IV methyl prednisolone and mycophenolate mofetil. PRIMARY OUTCOME The primary outcome is to demonstrate non-inferiority of the Rituximab arm in comparison to the control arm in the proportion of patients achieving complete renal response (CR) at week 52 without the need for steroid prescription. SECONDARY OUTCOMES Safety outcomes: * Serious Infectious Episodes * Serious Adverse Events * Evidence of metabolic abnormalities particularly new onset diabetes Disease control over time: * Proportion of patients achieving Partial Response (PR) * Time to stable CR * Time to PR * Proportion of patients in PR who achieve histological remission in those who have a repeat biopsy as part of local standard of care * Proportion of patients with renal or extra flare * Cumulative steroid exposure * Deviation from the steroid taper in the steroid arm and/or introduction of steroids in the steroid-free arm * Proportion of patients achieving a response as defined by the SLE Responder Index (SRI) at week 52 and annually thereafter as defined by: * a \>4 point reduction in SELENA-SLEDAI score; * no new BILAG A organ domain score; * no more than I new BILAG B score; * no worsening in physician's global assessment (PGA) by \>10%; * must not have received non-protocol treatment. * Proportion of patients achieving a response as defined by the BILAG-based Composite Lupus Assessment (BICLA) at week 52 and annually thereafter as defined by: BILAG-2004 improvement (BILAG A to B/C/D, BILAG B to C/D and no BILAG worsening, no deterioration in SLEDAI total score, no worsening in physician's global assessment (PGA) by \>10% and must not have received non-protocol treatment.