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Systemic Lupus Erythematosus, Lupus NephritisPhase 3RITUXILUPNCT01773616

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

A Phase 3 study testing Oral prednisolone, Rituximab and Mycophenolate mofetil in people with Systemic Lupus Erythematosus, Lupus Nephritis, run by Imperial College London at 11 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 75 years
What is being tested?
Oral prednisolone, Rituximab and Mycophenolate mofetil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
11 sitesUnited Kingdom
Study dates
Apr 2015to Dec 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • In female patients, known history of cervical dysplasia CIN Grade III cervical high risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) within the past 3 years. The patient will be eligible after the condition has resolved (e.g., follow-up HPV test is negative or cervical abnormality has been effectively treated >1 year ago)
  • Any concomitant medical condition or abnormal blood results that in the investigator's opinion, or after discussion with the CI, places the participant at risk by participating in this study.
  • Comorbidities requiring systemic corticosteroid therapy.
  • Current substance abuse.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United Kingdom11 sites
  • Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B15 2TH

  • Chapel Allerton Hospital, The Leeds Teaching Hospitals NHS Trust

    Leeds, LS7 4SA

  • Leicester General Hospital, University Hospitals of Leicester NHS Trust

    Leicester, LE5 4PW

  • Royal Free London NHS Foundation Trust

    London, NW3 2QG

  • Guy's and St Thomas' NHS Foundation Trust

    London, SE1 7EH

  • Hammersmith Hospital, Imperial College Healthcare NHS Trust

    London, W12 0HS

  • Great Ormond Street Hospital for Children NHS Foundation Trust

    London, WC1N 3JN

  • King's College Hospital

    London

  • Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust

    Manchester, M13 9WL

  • Churchill Hospital, Oxford University Hospitals NHS Trust

    Oxford, OX3 7LE

  • Royal Stoke Hospital, University Hospitals of North Midlands NHS Trust

    Stoke-on-Trent, ST4 6QG

Other trials in United Kingdom

About this study

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.

Read the 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.
Being tested
Oral prednisolone, Rituximab, Mycophenolate mofetil, Methyl prednisolone
Keywords
Systemic lupus erythematosus, Lupus, Nephritis
Medical subject headings
Lupus Erythematosus, Systemic, Lupus Nephritis, Nephritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01773616
Study groupRoleWhat they receive
RituximabExperimentalRituximab, methyl prednisolone and mycophenolate mofetil
Receives: Drug: Rituximab; Drug: Mycophenolate mofetil; Drug: Methyl prednisolone
Oral prednisoloneActive comparatorOral prednisolone, methyl prednisolone and mycophenolate mofetil
Receives: Drug: Oral prednisolone; Drug: Mycophenolate mofetil; Drug: Methyl prednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 1 year

Secondary outcomes (13)
  1. Serious Infectious Episodes, Serious Adverse Events and Adverse events

    1. Metabolic abnormalities related to steroid exposure: 5. Cumulative steroid exposure over 1 and 2 years 6. Introduction of oral steroids in the B cell depleted patients 7. Patients requiring >10mg oral prednisolone at 1 year and 2 year

    Measured: 2 years

  2. Metabolic abnormalities related to steroid exposure

    Measured: 2 years

  3. Cumulative steroid exposure over 1 and 2 years

    Measured: 2 years

  4. Introduction of oral steroids in the B cell depleted patients

    Measured: 2 years

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

    Measured: 2 years

  6. Proportion of patients achieving CR at 6, 18 and 24 months

    Measured: 2 years

  7. Proportion of patients achieving PR at 6,12,8 and 24 months

    PR is defined as:

    1. eGFR at baseline or <20% decrease, ii) AND if not nephrotic at baseline (PCR<300mg/mmol), 50% improvement in urine PCR iii) OR if nephrotic at baseline (PCR >300mg/mmol), 50% improvement in urine PCR AND PCR <300mg/mmol

    Measured: 2 years

  8. Mean time to stable CR and mean time to PR

    Measured: 2 years

  9. Proportion of patients in PR who achieve histological remission as judged by absence of proliferative lesions and no new subendothelial or subepithelial deposits

    Measured: 2 years

  10. Proportion of patients with only 1 or fewer BILAG 2004 Bs in any non-renal organ system at 1 year

    Measured: 2 years

  11. Proportion of patients with renal flare

    Flare is identified by:

    1. Proteinuria >50% increase ii) AND above 100mg/mmol for 2 visits iii) and / or in those with normal renal function and normal urinary sediment, a fall of >20% in eGFR on 2 occasions Where possible flare should be proven by repeat renal biopsy.

    Measured: 2 years

  12. Mean time to renal flare in patients achieving CR and PR

    Measured: 2 years

  13. Proportion of patients achieving normal serum C3,C4 and anti-dsDNA antibodies at week 52

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2013 (estimated)
  2. Study startApr 2015
  3. Primary completionDec 2017
  4. Study completionDec 2017

Why it stopped: Study assessments for patients recruited continuing per protocol so patients receive a minimum of 6 months follow up. No safety concerns have been raised.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01773616
Sponsor's protocol ID
CRO2035
Acronym
RITUXILUP
Status last verified
Jan 2018
First submitted
1 Nov 2012
Last updated
1 Feb 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral prednisolone, Rituximab and Mycophenolate mofetil in people with Systemic Lupus Erythematosus, Lupus Nephritis, run by Imperial College London at 11 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study assessments for patients recruited continuing per protocol so patients receive a minimum of 6 months follow up. No safety concerns have been raised.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete renal response (CR) at week 52 without the need to prescribe oral steroids within 1 year (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01773616, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2018.

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