NCT07502339

Upadacitinib in Patients Hospitalized With Acute Severe Ulcerative Colitis

An Open-Label, Investigator-Initiated Study Evaluating the Use of Upadacitinib in Patients Hospitalized With Acute Severe Ulcerative Colitis

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if the oral medication upadacitinib can safely and effectively treat acute severe ulcerative colitis (ASUC) in adults who are hospitalized. It will also evaluate whether upadacitinib can be used without corticosteroids during initial treatment. The main questions it aims to answer are: 1. Does upadacitinib reduce treatment failure by Day 14 (defined as need for colectomy or rescue therapy)? 2. What side effects and safety events occur when using upadacitinib in hospitalized patients with ASUC? Researchers will compare outcomes in participants receiving upadacitinib to a historical group of similar patients previously treated with standard therapies, including intravenous corticosteroids and infliximab, to determine if upadacitinib improves outcomes. Participants will: 1. Take oral upadacitinib once daily during hospitalization. 2. Undergo routine clinical monitoring, including blood tests and symptom assessments. 3. Be followed after discharge with clinic visits or phone calls for up to 12 months to assess outcomes such as need for additional treatment, surgery, and safety events

Detailed description

Acute severe ulcerative colitis (ASUC) is a medical emergency associated with high morbidity and colectomy rates despite standard treatment with intravenous corticosteroids and rescue therapy with biologics such as infliximab. Limitations of current therapies include delayed onset of action, need for intravenous administration, and significant corticosteroid-related toxicity. There remains an unmet need for rapidly acting, effective, and steroid-sparing treatment strategies in the inpatient setting. Upadacitinib is an oral selective Janus kinase 1 (JAK1) inhibitor approved for the treatment of moderate-to-severe ulcerative colitis. In Phase III trials (U-ACHIEVE and U-ACCOMPLISH), upadacitinib demonstrated rapid onset of action, with clinical improvement observed within days of initiation, as well as favorable corticosteroid-sparing effects. However, its use in hospitalized patients with ASUC has not been systematically evaluated in a prospective clinical study. This is a single-center, prospective, open-label, single-arm Phase IV clinical trial conducted at the University of California, San Francisco (UCSF). The study will evaluate oral upadacitinib 45 mg once daily as corticosteroid-free induction therapy in adults hospitalized with ASUC. Approximately 50 participants aged 18-75 years with established ulcerative colitis and meeting criteria for ASUC (Mayo score \>10 or Truelove and Witts criteria) will be enrolled. Participants will receive upadacitinib during hospitalization (target duration 5-7 days) and will be followed for 52 weeks to assess short-term and long-term outcomes. The primary endpoint is treatment failure by Day 14, defined as colectomy or need for rescue therapy with intravenous corticosteroids and/or infliximab. Secondary endpoints include safety outcomes such as serious adverse events, infections, thromboembolic events, and laboratory abnormalities. Exploratory endpoints include colectomy rates at multiple time points, time to colectomy, hospital length of stay, and 30-day readmission rates. Outcomes in the intervention cohort will be compared to a historical control group of ASUC patients treated at UCSF between March 2022 and June 2025 with infliximab-based regimens with or without corticosteroids. To reduce bias associated with the non-randomized design, propensity score matching and multivariable regression analyses will be used to adjust for baseline differences between groups. This study aims to generate prospective data on the feasibility, safety, and effectiveness of upadacitinib as a novel corticosteroid-free induction strategy in hospitalized patients with ASUC, with the potential to inform future treatment paradigms and reduce reliance on corticosteroids in this high-risk population.

Conditions

• UC - Ulcerative Colitis

Interventions

Type	Name	Description
DRUG	Upadacitinib	Upadacitinib is an oral selective Janus kinase 1 (JAK1) inhibitor. In this study, participants will receive upadacitinib 45 mg orally once daily during hospitalization as corticosteroid-free induction therapy for acute severe ulcerative colitis. After discharge, treatment will follow protocol-defined pathways: Participants who are advanced therapy-naïve may transition to an IL-23 inhibitor after 4 weeks. Participants with prior advanced therapy exposure may continue upadacitinib 45 mg for up to 8 weeks, followed by dose reduction to standard maintenance dosing (30 mg or 15 mg once daily) at the discretion of the treating physician. Treatment duration and adjustments may vary based on clinical response and safety.

Timeline

• Start date: 2026-07-01
• Primary completion: 2028-08-01
• Completion: 2028-08-01
• First posted: 2026-03-31
• Last updated: 2026-04-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study