Rituximab in Ulcerative Colitis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2004 by Royal Liverpool University Hospital.
Recruitment status was  Recruiting
Hoffmann-La Roche
Information provided by:
Royal Liverpool University Hospital
ClinicalTrials.gov Identifier:
First received: November 29, 2005
Last updated: February 1, 2006
Last verified: October 2004

November 29, 2005
February 1, 2006
April 2004
Not Provided
Remission defined as a decrease in Mayo score to ≤ 2 points at week 4
Same as current
Complete list of historical versions of study NCT00261118 on ClinicalTrials.gov Archive Site
  • Clinical response defined as a decrease in Mayo score by ≥ 3 points at weeks 4, 8 (partial Mayo score) and 12.
  • Remission at weeks 8 and 12.
  • Endoscopic mucosal healing at week 4 and 12
  • Improvement in Inflammatory Bowel Disease specific Quality of Life Index [22] [Appendix 2] at weeks 4 and 12
  • Histological improvement of disease activity at 4 and 12 weeks compared with baseline. Scored as follows:
  • 0 = no polymorphs
  • 1 = small numbers of polymorphs in the lamina propria with minimal infiltration of crypts
  • 2 = prominent polymorphs in the lamina propria with infiltration of ³ 50% of crypts
  • 3 = florid polymorph infiltrate with crypt abscesses
  • 4 = florid acute inflammation with ulceration
  • Treatment tolerability as defined by adverse events.
Same as current
Not Provided
Not Provided
Rituximab in Ulcerative Colitis
Phase 3: Randomised Controlled Trial of Rituximab in Active Ulcerative Colitis

There is broad support for the hypothesis that Ulcerative colitis is an auto-immune disease. Rituximab is an antibody protein that removes a subgroup of white blood cells (B lymphocytes) from the circulation. These cells have the capacity to generate the auto-antibodies that typify auto-immune disease. Although Rituximab has been mainly used for treating B lymphocyte malignancies (lymphoma) it has also been used with promising results in Rheumatoid arthritis and has an excellent safety recortd. This is a small placebo-controlled trial to assess its efficacy and safety in patients with steroid-resistant active ulcerative colitis.


Lack of effective cure for Ulcerative colitis.


That rituximab may be effective in active ulcerative colitis.


Rituximab has been used to treat more than 300,000 patients with B lymphocyte malignancies and has been shown to have an excellent safety record [6-8]. Published pilot studies have shown excellent results with rituximab in patients with autoimmune diseases such as immune-mediated thrombocytopaenia, Wegeners granulomatosis, cold agglutinin disease, myasthenia gravis, rheumatoid arthritis and SLE [11-17]. Together with increasing evidence to support a pathogenic role for the pANCA associated with ulcerative colitis, a study of rituximab in ulcerative colitis is timely. Moreover the only significant advance in the treatment of ulcerative colitis in recent years has been the introduction of cyclosporin which probably halves the colectomy rate [18,19] but at the risk of considerable side effects and with a drug-related mortality that has been estimated at 2%.


A Medline search for “ rituximab and ulcerative colitis” yielded no responses. There has been a recent report of its use in a single patient with ileocolonic Crohn’s disease who also had immune-mediated thrombocytopaenia [20]. The thrombocytopaenia improved but the Crohn’s disease did not. It can be argued though that there is little or no evidence for autoimmunity in Crohn’s disease which seems in many cases to be due to a defect in phagocyte function, eg in association with the recently described NOD2/CARD15 genetic alteration.

2.5 HOW WILL THE RESULTS OF THIS TRIAL BE USED? This trial will establish whether rituximab is effective in achieving remission in patients with ulcerative colitis who are failing to respond to conventional therapy with corticosteroids. Because there is no background evidence of its efficacy the initial study will be a small two centre study with placebo blinding. If the result of this study is promising, these would be used as pilot data for power calculations for a larger multicentre study.

3.1 WHAT IS THE PROPOSED TRIAL DESIGN? A “placebo-blinded” study with 16 patients receiving rituximab and 6 patients receiving placebo (0.9% saline).

3.2 WHAT ARE THE PLANNED TRIAL INTERVENTIONS? Patients will receive either (i) rituximab 1g in 500 mls of 0.9% saline infused into a peripheral vein over four hours (see appended infusion chart), or (ii) 500 mls of 0.9% saline infused into a peripheral vein over two hours as placebo. This regimen will be repeated once at 2 weeks. This protocol is based on the dosing regimen that proved most efficacious for rheumatoid arthritis. All patients will also receive paracetamol 1g orally and chlorpheniramine (Piriton) 10mg intravenously immediately prior to each Rituximab/placebo infusion.

All patients will continue to receive oral prednisolone 40mg/day for 2 weeks then 30mg for two weeks, then 20mgs/day for two weeks, then reduce by 5mg/day every 7 days until off prednisolone.



3.5 WHAT ARE THE PROPOSED OUTCOME MEASURES? see earlier 3.6 WILL HEALTH SERVICE RESEARCH ISSUES BE ADDRESSED? Not Applicable 3.7 WHAT IS THE PROPOSED FREQUENCY/DURATION OF FOLLOW UP? Patients will be reviewed after one, two and four, eight, twelve and twenty four weeks. Patients will be monitored thereafter in routine gastroenterology clinic follow up.

3.8 HOW WILL THE OUTCOME MEASURES BE MEASURED AT FOLLOW-UP? Patients will complete a daily diary with details of bowel frequency, presence of blood in the stool, any change in medical therapy and any new or worsening symptoms The IBD quality of life questionnaire will be completed at baseline and at weeks 4 and 12.

Patients will also have a diary card to record the details of any other symptoms noted during the trial to assess adverse effects of the trial treatment.

3.9 WHAT ARE THE PROPOSED PRACTICAL ARRANGEMENTS FOR ALLOCATING PATIENTS TO TRIAL GROUPS? Randomisation will be allocated in blocks of five by the pharmacy department of the hospital.

3.10 WHAT ARE THE PROPOSED METHODS FOR PROTECTING AGAINST OTHER SOURCES OF BIAS? Controls (known only to the Pharmacy Department) will receive a placebo saline infusion.

3.11 WHAT IS THE PROPOSED SAMPLE SIZE? A “placebo-blinded” study with 16 patients receiving rituximab and 8 patients receiving placebo (0.9% saline). This will provide 80% power for excluding an 80% remission rate with active treatment compared with an assumed 25% placebo response.


3.14 WHAT IS THE LIKELY RATE OF LOSS TO FOLLOW UP? 100% follow up should be achievable. 3.15 HOW MANY CENTRES WILL BE INVOLVED? Two 3.16 WHAT IS THE PROPOSED TYPE OF ANALYSIS? Formal hypothesis testing of the primary outcome will be compared by chi-square test.

Wilcoxon signed rank test will be used for comparisons against baseline for changes in secondary quantitative endpoints.

3.17 WHAT IS THE PROPOSED FREQUENCY OF ANALYSIS? Once only on completion. 3.18 ARE THERE ANY PLANNED SUBGROUP ANALYSES? Subgroup analysis may be performed according to pANCA status.

3.19 WHAT IS THE ESTIMATED RESEARCH COST OF THE TRIAL? Cost of therapy plus £800 pharmacy fee plus £2200 towards ethics submission/ research nurse time/ cost of pANCA assays to be provided as an unrestricted educational grant from Roche UK.

3.20 IS THERE AN NHS SERVICE SUPPORT COST OF THIS TRIAL, AND IF SO WHAT IS THE ESTIMATED COST? The only NHS cost would be modest, involving only the routine testing of full blood count and SMAC which is current practice in the monitoring of patients with relapses of inflammatory bowel disease.


  1. Quinton JF, Sendid B, Reumaux D et al. Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Gut 1998;42:788-91
  2. Xiao H, Heeringa P, Hu P et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest. 2002;110:955-63.
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Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Ulcerative Colitis
Drug: Rituximab
Not Provided
Leiper K, Martin K, Ellis A, Subramanian S, Watson AJ, Christmas SE, Howarth D, Campbell F, Rhodes JM. Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis. Gut. 2011 Nov;60(11):1520-6. doi: 10.1136/gut.2010.225482. Epub 2011 Apr 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
December 2007
Not Provided

Inclusion Criteria:

  1. Patients over age of 18 years who are capable of providing written informed consent.
  2. Confirmed diagnosis of ulcerative colitis by conventional clinical, endoscopic and histological criteria.
  3. Failure of response to at least two weeks of oral prednisolone 40mg/day.
  4. Active colitis as assessed by a Mayo score [21] of 6-12 inclusive (see Appendix 1)

Exclusion Criteria:

  1. Patients under 18 or unable to give informed consent.
  2. Patients in their first attack of ulcerative colitis.
  3. Patients with severe ulcerative colitis as defined by presence of any of: temperature >37.5oC, pulse rate >100, focal severe or rebound abdominal tenderness, haemoglobin < 10.0g/dl, serum albumin <3.5 g/dl, transverse colon diameter greater than 5.0cms on plain abdominal X ray.
  4. Patients who are pregnant, post partum (<3months) or breast feeding
  5. Patients who are at risk of pregnancy and not using a reliable form of contraception (oral contraceptive and barrier or barrier plus spermicide).
  6. Patients with a stoma
  7. Positive stool culture for pathogens or test for C difficile at screening within 7 days prior to trial entry
  8. Patients for whom a baseline Mayo score can not be reliably calculated: frequent use of laxatives (for proximal constipation) or antimotility agents (for control of diarrhoea)
  9. Any change to maintenance medication for ulcerative colitis: azathioprine or 6-mercaptopurine within previous 3 months or 5-aminosalicylates within previous one month
  10. Any change to rectal therapy for colitis within the previous two weeks.
  11. Participation in other trials in the last 3 months.
  12. Serious intercurrent infection or other clinically important active disease (including renal and hepatic disease)


18 Years and older
Contact: Kate Martin, RGN 441517064194 kate.martin@rlbuht.nhs.uk
Contact: Jonathan M Rhodes, MD 441517064073 rhodesjm@liverpool.ac.uk
United Kingdom
RLBUHT R&D 2709, DDX exemption from MRHA ref:-, MF 8000/12794
Not Provided
Not Provided
Royal Liverpool University Hospital
Hoffmann-La Roche
Principal Investigator: Jonathan M Rhodes, MD University of Liverpool
Royal Liverpool University Hospital
October 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP