Acute Severe Ulcerative Colitis MedDRA version: 20.0 Level: LLT Classification code 10066678 Term: Acute ulcerative colitis System Organ Class: 100000016670
Conditions
Interventions
Trade Name: Anakinra
Product Name: Anakinra
Product Code: N/A
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or P
Sponsors
Cambridge University Hospitals NHS Foundation Trust & University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients aged 16-80 inclusive - Have given written informed consent to participate - Hospitalised patients with clinically confirmed or suspected acute severe ulcerative colitis and a Modified Truelove Witts Severity Index score =11 - Requirement for treatment with IV corticosteroids in the judgement of the treating clinician, with the possibility to receive a first dose of IMP within 36 hours of commencement of IV corticosteroids Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Pregnant or breast-feeding women - Oral corticosteroid dosing for a duration of 8 weeks or more immediately prior to commencement of IV corticosteroid dosing - History of severe hepatic impairment (e.g. Child-Pugh = Grade C) - Moderate or severe renal impairment (eGFR <50ml/minute) - Neutropenia (neutrophil count <1.5x109/l) - Previous treatment with anakinra for any indication - Evidence (from blood cultures etc) or clinical suspicion of systemic infection - Current or previous cytomegalovirus (CMV) infection requiring treatment with anti-viral agents - Current treatment with anti-TNF-a therapy or anti-TNF-a discontinuation within previous 16 weeks - A history of pulmonary TB infection - History of malignancy (with the exception of non-melanoma skin cancer) or colonic dysplasia - Receipt of another IMP as part of a CTIMP within the previous 16 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The trial will also compare the effects of anakinra with placebo when given in addition to current standard care in terms of: - Whether either treatment results in a difference in the number of cases of colectomy (surgical removal of the colon) - How safe both treatments are - The quality of life associated with both treatments, as reported by participants - The extent to which either treatment has an effect on the molecular mechanisms which can trigger ulcerative colitis ; Main Objective: The aim of this trial is to compare the clinical effects of anakinra with placebo when given in addition to current standard care in patients with acute severe ulcerative colitis. The primary measure of success will be any difference in the proportion of participants in the group receiving anakinra who needed escalation to more intensive medical or surgical therapy (known as rescue therapy) by 10 days after standard treatment was started, when compared with the group of participants receiving placebo. ;Primary end point(s): The incidence of medical or surgical rescue therapy within 10 days following the commencement of intravenous corticosteroid therapy.;Timepoint(s) of evaluation of this end point: 10 days after the commencement of intravenous corticosteroid therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Incidence of colectomy within 98 days following the commencement of IV corticosteroid therapy, assessed via review of medical records or by follow up telephone call. 2.Burden of disease activity, measured by daily modified Truelove and Witts severity index (MTWSI) scores. 3.Time to clinical response (defined as 2nd consecutive day with MTWSI <10). 4.Time to medical or surgical rescue therapy, measured according to the time after the first dose of IV corticosteroids until the time that rescue therapy occurs. 5.Incidence of serious adverese events (SAEs) assessed via review of medical records or by follow up telephone call. ; Timepoint(s) of evaluation of this end point: 1.Incidence of Colectomy: 98 days after the commencement of IV corticosteroid therapy 2.Burden of disease activity: Daily MTWSI scores at baseline and over Days 1-5 after initial IMP administration. 3.Time to clinical response: During the inpatient stay, between Day 1-5 after initial IMP administration. 4.Time to medical or surgical rescue therapy: Data will be captured up to 10 days after commencement of IV corticosteroids. 5.Incidence of SAEs: Measured until Day 10 (+3) following administration of first IMP dose. | — |
Countries
United Kingdom
Contacts
Public ContactCarrie Bayliss
Cambridge Clinical Trials Unit
Outcome results
None listed