Rituximab in Active Ulcerative Colitis

NCT00261118 | Completed Phase 2 DMC

• 3 other identifiers: RLBUHT R&D 2709DDX exemption from MRHA ref:-MF 8000/12794
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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 record. This is a small placebo-controlled trial to assess its efficacy and safety in patients with steroid-resistant active ulcerative colitis.

Conditions

Ulcerative Colitis

Keywords

colitis; rituximab

Outcome Measures

Primary Outcomes (1)

• Remission defined as a decrease in Mayo score to ≤ 2 points at week 4

  week 4

Secondary Outcomes (6)

• Clinical response defined as a decrease in Mayo score by ≥ 3 points at weeks 4, 8 (partial Mayo score) and 12.

  Week 4, 8 & 12

• Remission at weeks 8 and 12.

  week 8 &12

• Endoscopic mucosal healing at week 4 and 12

  Week 4 & 12

• Improvement in Inflammatory Bowel Disease specific Quality of Life Index at weeks 4 and 12

  weeks 4 &12

• Histological improvement of disease activity at 4 and 12 weeks compared with baseline.

  week 4 & 12 weeks

Study Arms (2)

1 (i)

ACTIVE COMPARATOR

Rituximab 1g in 500 mls of 0.9% normal saline infused into a peripheral vein

Drug: Rituximab

2 (ii)

PLACEBO COMPARATOR

500 mls of 0.9% NORMAL SALINE INFUSED INTO A PERIPHERAL VEIN

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab 1g in 500 mls Normal Saline Placebo 500 mls Normal Saline

Also known as: MabThera (Roche)

1 (i); 2 (ii)

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Patients under 18 or unable to give informed consent.
• Patients in their first attack of ulcerative colitis.
• 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.
• Patients who are pregnant, post partum (\<3months) or breast feeding
• Patients who are at risk of pregnancy and not using a reliable form of contraception (oral contraceptive and barrier or barrier plus spermicide).
• Patients with a stoma
• Positive stool culture for pathogens or test for C difficile at screening within 7 days prior to trial entry
• 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)
• Any change to maintenance medication for ulcerative colitis: azathioprine or 6-mercaptopurine within previous 3 months or 5-aminosalicylates within previous one month
• Any change to rectal therapy for colitis within the previous two weeks.
• Participation in other trials in the last 3 months.
• Serious intercurrent infection or other clinically important active disease (including renal and hepatic disease)

Sponsors & Collaborators

• Royal Liverpool University Hospital: lead
• Hoffmann-La Roche: collaborator
• University of Liverpool: collaborator

Study Sites (1)

Royal Liverpool University Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Related Publications (23)

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  PMID: 21471566 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Colitis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jonathan M Rhodes, MD

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Invesitgator

Study Record Dates

• First Submitted: November 29, 2005
• First Posted: December 2, 2005
• Study Start: April 1, 2004
• Primary Completion: August 1, 2009
• Study Completion: October 1, 2009
• Last Updated: November 6, 2014

Record last verified: 2014-11

Locations

GB (1)