NCT01773616

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

Phase 3 Open Label Randomised Multicentre Controlled Trial of Rituxmab and Mycophenolate Mofetil Without Oral Steroids for the Treatment of Lupus Nephritis

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 12 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The treatment of the multisystem autoimmune disease systemic lupus erythematosus (SLE) remains a challenge, particularly when there is renal involvement (lupus nephritis). For the last 60 years corticosteroids have been the backbone of the treatment of lupus nephritis but they are associated with significant toxicity. Although randomized placebo controlled trials of Rituximab in non-renal lupus and lupus nephritis did not meet their primary end-points, there is accumulating data that suggests that B cell depletion with Rituximab may be efficacious in lupus disease refractory to conventional therapy. Furthermore, our pilot data suggests that the addition of Rituximab to mycophenolate mofetil (MMF) without oral steroids is at least as effective at inducing a renal response as the standard of care therapy comprising MMF and high dose oral corticosteroids. RITUXILUP is a proof of concept, open labeled, randomized, controlled, multicentre trial that aims to demonstrate whether the addition of Rituximab to MMF therapy is useful in treating a new flare of lupus nephritis and whether it has a long lasting steroid-sparing, beneficial effect with equal efficacy and greater safety than a conventional regimen of MMF and oral prednisolone. If successful, this trial has the potential to dramatically change the management of lupus nephritis.

Detailed description

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.

Conditions

• Systemic Lupus Erythematosus, Lupus Nephritis

Interventions

Type	Name	Description
DRUG	Oral prednisolone
DRUG	Rituximab
DRUG	Mycophenolate mofetil
DRUG	Methyl prednisolone

Timeline

• Start date: 2015-04-01
• Primary completion: 2017-12-01
• Completion: 2017-12-01
• First posted: 2013-01-23
• Last updated: 2018-02-01

Locations

11 sites across 1 country: United Kingdom