Acute severe ulcerative colitis Digestive System
Conditions
Interventions
Double blind placebo controlled
Investigation arm: Upadacitinib 45mg orally + Standard care
Comparator arm : Placebo orally + Standard care
Stratification: Prior steroid use, Prior Infliximab use
D
Sponsors
Hull University Teaching Hospitals NHS Trust
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Patients aged 18 – 65 years inclusive 2. Have given written informed consent to participate 3. Hospitalised patients with clinically confirmed or suspected ASUC 4. Modified Truelove and Witts severity index (MTWSI) score = 11 5. Requirement for treatment with IV corticosteroids in the judgement of the treating clinician and the possibility to receive the IMP within 36 hours of admission
Exclusion criteria
Exclusion criteria: 1. Patients with any absolute contraindication to Upadacitinib 2. Proven infective colitis within 4 weeks of baseline assessment (Stool Cultures or C Diff Toxin assay positive, Cytomegalovirus (CMV) on biopsies) 3. Pregnant patients or patients breast feeding 4. Patients with toxic megacolon (TMC) at baseline assessment prior to randomisation 5. Use of strong CYP3A4 inhibitor medications (azoles, clarithromycin) and co-administration of food and drink containing grapefruit 6. Use of strong CYP3A4 inducer medications (including Rifampicin and Phenytoin) 7. Recent history of incompletely treated malignancy within 12-months (patients with a solid organ malignancy that remains under active treatment or where oncologists have not confirmed complete eradication) 8. Neutropenia with baseline ANC 2.5 the upper limit of normal 14. Patients with personal history of confirmed Venous Thromboembolism (VTE)/Pulmonary Embolism (PE) who are not on effective anticoagulation (e.g. history of previous Deep Vein Thrombosis ((DVT) or PE)) but no longer requiring anticoagulation, history of previous DVT or PE requiring anticoagulation where anticoagulation was not tolerated or withdrawn because of side-effects) 15. Evidence (from blood cultures etc) or clinical suspicion of systemic infection 16. English not adequate in absence of local translation service (i.e. patient unable to comprehend trial patient information sheet) 17. Currently taking part in another Clinical Trial of an Investigational Medicinal Product [CTIMP] 18. Treatment with other Janus kinase (JAK) inhibitors (e.g. Tofacitinib or Filgotinib) within 4 weeks of the time of screening 19. Patients previously exposed to Upadacitinib as per local label 20. Patients with risk factors for MACE/malignancy unless no suitable treatment alternatives available 21. A history of untreated pulmonary Tuberculosis (TB) infection 22. Any absolute contraindication to corticosteroid 23. Patients with administered live vaccines of replication potential within 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Need for medical or surgical rescue therapy within 10 days following commencement of IV corticosteroids therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Percentage of patients who achieve clinical response at Day 10 from baseline (MTWSI reduction =3 points and MTWSI < 10) 2. Time to clinical response (MTWSI reduction =3 points + MTWSI <10) 3. Time to rescue therapy (medical or surgical) (MTWSI) 4. Percentage of patients who meet Oxford Travis rescue criteria for rescue therapy on or beyond Day 3 of hospitalisation 5. Percentage of patients who achieve clinical remission at 10 days and 8 weeks (Mayo stool frequency sub-score of 0 or 1, and rectal bleeding sub-score of 0) 6. Percentage of patients who achieve biomarker remission at 10 days and 8 weeks (CRP = 5mg/L, calprotectin = 250µg/g where available) 7. Percentage of patients who achieve endoscopic remission at 8 weeks where data available (endoscopic Mayo sub-score 0-1) 8. Incidence of colectomy within 8 weeks following commencement of IV corticosteroid therapy 9. Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) 10. Total duration of hospital stay | — |
Countries
United Kingdom
Contacts
Public ContactMahboobeh Haji Sadeghi
Outcome results
None listed