This trial is being conducted to learn more about the optimal sequence of various medications in the management of acute severe ulcerative colitis (ASUC).
This research is studying multiple drugs already approved by the Food and Drug Administration (FDA). The goal of this study is to test the early efficacy and safety of upadacitinib (Rinvoq) and corticosteroids compared to corticosteroids alone as induction therapy for both inpatients and outpatients with ASUC.
Patient ≥ 18 to 75 years of age at the time of consent
Diagnosis of ulcerative colitis (verified by a typical clinical history as well as characteristic appearance on endoscopy and histology)
For a person of reproductive/childbearing potential (i.e., presence of intact ovaries and fallopian tubes and are considered premenopausal by standard assessment), a negative lab-based (serum/urine) pregnancy test is required.
For a person of reproductive potential (i.e., presence of intact ovaries and fallopian tubes) and has childbearing potential, intent to use at least one effective method of birth control from study Day 0 through the end of blinding or at least 30 days after the last dose of upadacitinib or week 48, whichever occurs most recently. A person without reproductive or childbearing potential does not require an intent to use effective birth control.
On IV corticosteroids for > 72 hours immediately prior to enrollment continuously (at any institution) which is equivalent to a cumulative dose of 180mg of IV Methylprednisolone in the 3 days prior to enrollment.
Patients with a prior exposure upadacitinib. Previous exposure to other Janus kinase (JAK) inhibitors (e.g., tofacitinib, baricitinib, or filgotinib) are permissible.
History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months prior to Baseline. (Note: A Urine Drug Screen does not need to be performed).
A history of two or more prior episodes of herpes zoster, or one or more episodes of disseminated herpes zoster.
Parallel
Oral Upadacitinib
DrugDoses start at 45milligrams (mg) during acute induction and post-acute induction phase (total of 8 weeks). During the Dose Optimization Maintenance Phase, unrescued participants not undergoing colectomy will continue upadacitinib therapy through week 48, with dosage (45 mg, 30 mg, or 15 mg) titrated based on clinical symptoms and inflammatory biomarkers.
Intravenous Methylprednisolone
DrugIntravenous (IV) given 60mg daily (in divided or full doses). Inpatients will receive this in the hospital. Outpatient participants can get this at an infusion center. Following completion of the Acute Induction Phase (inpatient cohort: 0-10 days ending at discharge; outpatient cohort: 5 days), participants will be placed on a tapering dose of prednisone.
Oral Upadacitinib Placebo
DrugThe placebo will be discontinued at discharge for the inpatient cohort and after day 5 for the outpatient cohort.
Oral prednisolone Taper
DrugFollowing completion of the Acute Induction Phase (inpatient cohort: 0-10 days ending at discharge; outpatient cohort: 5 days), participants will be placed on a tapering dose of prednisone. Participants randomized to the corticosteroid arm will be placed on prednisone at a dose 40mg to be tapered by 5mg/week. Participants randomized to the upadacitinib and corticosteroid arm will be placed on 2 weeks of prednisone (40mg x 2 days, 30mg x 2 days, 25mg x 2 days, 20mg x 2 days, 15mg x 2 days, 10mg x 2 days, and 5mg x 2 days).
Oral Prednisone - Hospital Dose Steroids
DrugOral Prednisone 75mg daily can be given for 5 days to participants enrolled in the Outpatient Cohort as an alternative to getting IV methylprednisolone 60mg in an infusion center. Following completion of the Acute Induction Phase, participants will be placed on a tapering dose of prednisone.
The proportion of participants with an initial clinical response without rescue therapy or colectomy by treatment Day 5 after initiating induction therapy in the upadacitinib and corticosteroid arm compared to the corticosteroid monotherapy arm
Initial Clinical Response Definition: * A reduction in liquid bowel movements per 24 hours by ≥ 60% from randomization AND a C-reactive protein (CRP) \< 1.5 milligrams per deciliter (mg/dL) AND no more than trace blood in stool, or * 4 liquid bowel movements or less per 24 hours AND a C-reactive protein (CRP) \< 1.5 mg/dL AND no more than trace blood in stool. Liquid bowel movements are defined as completely liquid (Bristol stool chart type 7) or mostly liquid (Bristol stool chart type 8). If the patient is discharged prior to outcome assessment on treatment Day 5, the most recent CRP prior to treatment Day 5 will be to evaluate primary outcome (carry forward manner). If a patient has not experienced CRP improvement to \<1.5mg/dL prior to discharge, patient will be requested to obtain a treatment Day 5 CRP as an outpatient lab on treatment Day 5.
The proportion of participants in the outpatient cohort with a hospital admission by end of the acute induction phase (Day 5) in the upadacitinib and corticosteroid arm compared to the corticosteroid monotherapy arm.
The proportion of participants undergoing colectomy without rescue therapy by the end of the post-acute induction phase (week 8/day 56) in the upadacitinib and corticosteroid arm compared to the corticosteroid monotherapy arm
The proportion of participants undergoing colectomy without rescue therapy by week 12/Day 84 in the upadacitinib and corticosteroid arm compared to the corticosteroid monotherapy arm
The proportion of participants undergoing colectomy without rescue therapy by Week 48/Day 336 in the upadacitinib and corticosteroid arm compared to the corticosteroid monotherapy arm
Click on the lead sponsor to view all of their trials.
