ACESO trial: Upadacitinib Co-therapy with Corticosteroids in Early Acute Severe Ulcerative Colitis (A Phase III randomised placebo controlled double blinded trial)
Acute severe ulcerative colitis
Double blind placebo controlled Investigation arm: Upadacitinib 45mg orally + Standard care Comparator arm : Placebo orally + Standard care Stratification: Prior steroid use, Prior Infliximab use Duration of treatment : 2 months
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
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 <1 x 10^9 cells/L 9. Absolute Lymphocyte Count <1 x 10^9 cells/L 10. Hb <80 g/L 11. Moderate or Severe renal impairment (estimated glomerular filtration rate [eGFR] <40ml/min/1.73m²) 12. Severe hepatic impairment (Child-Pugh C) 13. ALT or AST >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anticoagulation, history of previous DVT or PE requiring anticoagulation where anticoagulation was not tolerated or withdrawn because of side-effects) 15.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