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

NCT01773616 | Terminated Phase 3 DMC

• 1 other identifier: CRO2035
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Systemic Lupus Erythematosus, Lupus Nephritis

Keywords

Systemic lupus erythematosus; Lupus; Nephritis

Outcome Measures

Primary Outcomes (1)

• Complete renal response (CR) at week 52 without the need to prescribe oral steroids within 1 year

  The proportion of participants who achieve a complete renal response at week 52 without the need to prescribe oral steroids within 1 year, except for one course of maximum 30mg for a maximum of 14 days OR one intramuscular or intra-articular injection of steroids

  1 year

Secondary Outcomes (13)

• Serious Infectious Episodes, Serious Adverse Events and Adverse events

  2 years

• Metabolic abnormalities related to steroid exposure

  2 years

• Cumulative steroid exposure over 1 and 2 years

  2 years

• Introduction of oral steroids in the B cell depleted patients

  2 years

• Patients requiring >10mg oral prednisolone at 1 year and 2 year

  2 years

Other Outcomes (7)

• Patients requiring repeat dosing with Rituximab

  2 years

• Patients requiring the addition of any new cytotoxic

  2 years

• Patients with non-renal BILAG 2004 A scores or flare and time to A flare

  2 years

Study Arms (2)

Rituximab

EXPERIMENTAL

Rituximab, methyl prednisolone and mycophenolate mofetil

Drug: Rituximab; Drug: Mycophenolate mofetil; Drug: Methyl prednisolone

Oral prednisolone

ACTIVE COMPARATOR

Oral prednisolone, methyl prednisolone and mycophenolate mofetil

Drug: Oral prednisolone; Drug: Mycophenolate mofetil; Drug: Methyl prednisolone

Interventions

Oral prednisolone DRUG

Oral prednisolone

Rituximab DRUG

Also known as: MabThera

Rituximab

Mycophenolate mofetil DRUG

Also known as: Cellcept, Myfenax

Oral prednisolone; Rituximab

Methyl prednisolone DRUG

Oral prednisolone; Rituximab

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• Obsolescence of \>50% of the glomeruli or tubulointerstitial scarring of \>50% or cellular crescents in \>50% of the glomeruli
• Severe "critical" SLE flare defined as:
• BILAG 2004 A flare in CNS system
• or any SLE manifestation requiring more immunosuppression than allowed within the protocol in the physician's opinion
• Pregnant or lactating. Woman who have child bearing potential must have two negative pregnancy test results with a sensitivity of ≥ 25 mIU/mL: one from a serum pregnancy test at day -8 to day -10 of screening and another from a urine pregnancy test at day 1 prior to randomisation. If the timeline is shortened because of clinical urgency, then there must be a negative serum pregnancy test with a sensitivity of ≥ 25 mIU/mL within 1-2 days before study start
• Patients not willing for their GP to be informed of their participation in this study
• Patients should not be on or require maintenance steroids and should not have had more than 12 weeks of steroids in the period immediately preceding recruitment irrespective of dose
• Patients that had received more than 2.0g of IV methyl prednisolone in the previous 4 weeks
• Prior use within 12 months of screening visit of therapeutic monoclonal antibody, or B or T cell modulating 'biologic' use
• Prior use within 6 months of the screening visit of Intravenous immunoglobulin / plasma exchange OR Cyclophosphamide
• Active infections, including but not limited to the human immunodeficiency virus (HIV), and hepatitis B (including prior infection as judged by positive Hepatitis B core antibody) or Hepatitis C or tuberculosis
• Receipt of a live-attenuated vaccine within 3 months of study enrolment
• In the investigator's opinion, patients that are at high risk for infection (including but not limited to indwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent severe urinary tract infection)
• Prior history of invasive fungal infections
• History of any cancer

Sponsors & Collaborators

• Imperial College London: lead
• Karolinska Institutet: collaborator
• Ohio State University: collaborator
• Dutch Working Party on Systemic Lupus Erythematosus: collaborator
• EULAR Lupus Nephritis Trial Network Study Group: collaborator

Study Sites (11)

Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Chapel Allerton Hospital, The Leeds Teaching Hospitals NHS Trust

Leeds, LS7 4SA, United Kingdom

Location

Leicester General Hospital, University Hospitals of Leicester NHS Trust

Leicester, LE5 4PW, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

Hammersmith Hospital, Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JN, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Churchill Hospital, Oxford University Hospitals NHS Trust

Oxford, OX3 7LE, United Kingdom

Location

Royal Stoke Hospital, University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (1)

• If Rituximab together with MMF is shown to be as good as standard treatment with MMF and oral steroids, it would be the first time in 60 years that patients with lupus nephritis could be spared the burden of long term steroids.

  BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis; Nephritis

Interventions

Prednisolone; Rituximab; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Liz Lightstone, Dr

  Imperial College London

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: January 23, 2013
• Study Start: April 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 1, 2018

Record last verified: 2018-01

Locations

GB (11)