Systemic Lupus Erythematosus, Lupus Nephritis Clinical Trial
Official title:
Phase 3 Open Label Randomised Multicentre Controlled Trial of Rituxmab and Mycophenolate Mofetil Without Oral Steroids for the Treatment of Lupus Nephritis
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.
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.
;