Upadacitinib Combined With Corticosteroids vs Corticosteroid Monotherapy Induction for Inpatients and Outpatients With Acute Severe Ulcerative Colitis

NCT07258771 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: HUM00266952
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis Acute

Keywords

Acute Severe Ulcerative Colitis; Inpatient; Outpatient; Optimal sequence; Upadacitinib; Corticosteroids

Outcome Measures

Primary Outcomes (1)

• 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.

  Treatment 5 days

Secondary Outcomes (22)

• 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.

  Day 5

• 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

  Week 8 (day 56)

• 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

  Week 12 (Day 84)

• 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

  Week 48 (Day 336)

• The proportion of participants in clinical response without colectomy or rescue therapy by end of post-acute induction phase (week 8/day 56) in the upadacitinib and corticosteroid arm compared corticosteroid monotherapy arm

  Week 8 (day 56)

Study Arms (4)

Upadacitinib plus steroids-Outpatient cohort

EXPERIMENTAL

This will include patients who meet acute severe ulcerative colitis criteria who are seen in clinic, that contact the clinic, or are sent to the ambulatory, diagnostic and treatment unit (ADTU) without requiring an admission to the hospital. Participants will receive upadacitinib 45mg and hospital dose steroids (IV Methylprednisolone 60mg in an infusion center or ADTU or PO Prednisone 75mg) up to Day 5. If the participant's condition does not improve or if it worsens after 3 days from starting assigned treatment, the participant will be unblinded and put on "rescue therapy". Unrescued participants will be unblinded on Day 5 when the Acute Induction Phase is complete. Upon completion of the Acute Induction Phase, participants will receive upadacitinib 45 mg for 8 weeks concomitant with a 2-week prednisone course. Upadacitinib therapy may continue through week 48, with dosage (45 mg, 30 mg, or 15 mg) titrated based on clinical symptoms and inflammatory biomarkers.

Drug: Oral Upadacitinib; Drug: Intravenous Methylprednisolone; Drug: Oral prednisolone Taper; Drug: Oral Prednisone - Hospital Dose Steroids

Steroids plus Upadacitinib Placebo-Outpatient cohort

ACTIVE COMPARATOR

This will include patients who meet acute severe ulcerative colitis criteria who are seen in clinic, that contact the clinic, or are sent to the ambulatory, diagnostic and treatment unit (ADTU) without requiring an admission to the hospital. Participants will receive upadacitinib placebo and hospital dose steroids (IV Methylprednisolone 60mg in an infusion center or ADTU or PO Prednisone 75mg) up to Day 5. If the participant's condition does not improve or if it worsens after 3 days from starting assigned treatment, the participant will be unblinded and put on "rescue therapy". Unrescued participants will be unblinded on Day 5 to guide selection of maintenance therapy. Upon completion of the Acute Induction Phase, participants will receive taper prednisone by 5mg per week starting at 40mg with maintenance therapy initiation per usual care.

Drug: Intravenous Methylprednisolone; Drug: Oral Upadacitinib Placebo; Drug: Oral prednisolone Taper; Drug: Oral Prednisone - Hospital Dose Steroids

Upadacitinib plus steroids- Inpatient cohort

EXPERIMENTAL

This will include patients seen in the Emergency Department or who are hospitalized. Participants will receive upadacitinib 45mg and hospital dose steroids (IV Methylprednisolone 60mg) until they are discharged. If the participant's condition does not improve or if it worsens after 3 days from starting assigned treatment, the participant will be unblinded and put on "rescue therapy". Unrescued participants will be unblinded as soon as participants are discharged (completion of the Acute Induction Phase). Upon completion of the Acute Induction Phase, participants will receive upadacitinib 45 mg for 8 weeks concomitant with a 2-week prednisone course. Upadacitinib therapy may continue through week 48, with dosage (45 mg, 30 mg, or 15 mg) titrated based on clinical symptoms and inflammatory biomarkers.

Drug: Oral Upadacitinib; Drug: Intravenous Methylprednisolone; Drug: Oral prednisolone Taper

Steroids plus Upadacitinib Placebo- Inpatient cohort

ACTIVE COMPARATOR

This will include patients seen in the Emergency Department or who are hospitalized. Participants will receive upadacitinib placebo and hospital dose steroids (IV Methylprednisolone 60mg) until they are discharged. If the participant's condition does not improve or if it worsens after 3 days from starting assigned treatment, the participant will be unblinded and put on "rescue therapy". Unrescued participants will be unblinded as soon as participants are discharged (completion of the Acute Induction Phase) to guide maintenance therapy selection (outside of the trial protocol). Upon completion of the Acute Induction Phase, participants will taper prednisone by 5mg per week starting at 40mg with maintenance therapy initiation per usual care.

Drug: Intravenous Methylprednisolone; Drug: Oral Upadacitinib Placebo; Drug: Oral prednisolone Taper

Interventions

Oral Upadacitinib DRUG

Doses 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.

Also known as: Rinvoq

Upadacitinib plus steroids- Inpatient cohort; Upadacitinib plus steroids-Outpatient cohort

Intravenous Methylprednisolone DRUG

Intravenous (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.

Also known as: Solumedrol

Steroids plus Upadacitinib Placebo- Inpatient cohort; Steroids plus Upadacitinib Placebo-Outpatient cohort; Upadacitinib plus steroids- Inpatient cohort; Upadacitinib plus steroids-Outpatient cohort

Oral Upadacitinib Placebo DRUG

The placebo will be discontinued at discharge for the inpatient cohort and after day 5 for the outpatient cohort.

Also known as: Placebo

Steroids plus Upadacitinib Placebo- Inpatient cohort; Steroids plus Upadacitinib Placebo-Outpatient cohort

Oral prednisolone Taper DRUG

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. 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).

Also known as: Prednisone

Steroids plus Upadacitinib Placebo- Inpatient cohort; Steroids plus Upadacitinib Placebo-Outpatient cohort; Upadacitinib plus steroids- Inpatient cohort; Upadacitinib plus steroids-Outpatient cohort

Oral Prednisone - Hospital Dose Steroids DRUG

Oral 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.

Also known as: prednisone

Steroids plus Upadacitinib Placebo-Outpatient cohort; Upadacitinib plus steroids-Outpatient cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Meeting the following definition of acute severe ulcerative colitis as defined as having ≥ 6 bowel movements per day with visible blood in the 7 days prior to Day 0 plus at least one of the following:
• i. Temperature \> 37.8 Celsius(C) per patient report or documented in Electronic Health Record (EHR) in the 7 days prior to Day 0.
• ii. Pulse ≥ 90 beats per minute (BPM) per patient report or documented in EHR iin the 7 days prior to Day 0 iii. Hemoglobin ≤ 10.5 grams per deciliter (g/dL) in the 7 days prior to Day 0 iv. Erythrocyte sedimentation rate ≥ 30 millimeters per hour (mm/h) in the 7 days prior to Day 0 v. C-reactive protein ≥ 3.0mg/dL in the 7 days prior to Day 0 vi. Fecal calprotectin \>782 Milligrams per kilogram (mg/kg) in the 7 days prior to consent.
• vii. Oral corticosteroid use for ≥ 7 days in the month prior to consent at a dose equivalent to ≥ 20 milligrams per day (mg/day)
• 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.
• Participants enrolled in the outpatient cohort must be under the care of an outpatient gastroenterologist affiliated with the University of Michigan.
• Ability to take oral medication and be willing to adhere to the study intervention regimen.
• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, daily bowel movement symptoms surveys, and other study procedures.
• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.

You may not qualify if:

• 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.
• Patients with ongoing severe active infection (as determined by the study team) per investigator. Patients with active serious infection(s) requiring treatment with intravenous anti-infectives or oral/intramuscular anti-infectives may consider infectious disease clearance.
• Active tuberculosis (TB) or untreated latent TB as described in the protocol.
• In participants that tested positive for Coronavirus disease 2019 (COVID-19), at least 5 days must have passed between a COVID-19 positive test result and the baseline visit of asymptomatic participants. Participants with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Participants may be rescreened if deemed appropriate by the investigator based upon the participant's health status.
• Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, or aorto-coronary bypass surgery.
• Known hypersensitivity to the following drugs or constituents (and its excipients): methylprednisolone, prednisone, upadacitinib, or upadacitinib placebo. The following ingredients can be found in upadacitinib and upadacitinib placebo: colloidal silicon dioxide, hypromellose, iron oxide yellow and iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, talc, tartaric acid and titanium dioxide. This includes a known or suspected hypersensitivity to cow's milk for patients expected to be in the inpatient cohort (component of methylprednisolone).
• Participants that are currently pregnant or breastfeeding. Participants with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥ 3 days later to document continued lack of a positive result. Participants with a urine pregnancy test at Baseline that is borderline or ambiguous must have a serum pregnancy test performed. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Participants that have received any live vaccine with replicating potential within 30 days prior to the first dose of study drug or are expected to need a live vaccination with any replicating potential during study participation or within 30 days of study completion.
• Patients that meet diagnostic criteria for toxic megacolon as determined by the study and treatment team. Patients are expected to have dilation of the transverse colon \> 6 centimeters (cm) or cecum/right colon \> 9cm and three of the following signs of systemic toxicity (Temperature \> 38◦C, Heart rate (HR) \> 120 beats per minute (BPM), white blood cells (WBC) \> 10500/microliter (µL), Hemoglobin \< 10.5mg/dL) and one of the following (dehydration, altered mental status, severe electrolyte disturbances, or hypotension)
• Patients that had received any investigational agent or procedure within 30 days or five half-lives prior to baseline, whichever is longer, or were enrolled in an interventional study.
• Patients with an active malignancy with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
• Patients that had a history of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy or were planning bowel surgery (partial colectomy is permissible)

Sponsors & Collaborators

• Berinstein, Jeffrey: lead
• AbbVie: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Interventions

upadacitinib; Methylprednisolone Hemisuccinate; Prednisone

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Jeffrey Berinstein, MD, MSc

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Queen Saunyama

CONTACT

734-647-2564; saunayma@umich.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine

Model Details: This study will implement a partially double-blind design, where the inpatient/outpatient treatment team, investigators, and participants will be blinded to the assigned treatment throughout the acute induction phase. If rescue therapy is initiated the outpatient or inpatient group the participants will be unblinded. For participants in the inpatient cohort that do not receive rescue therapy, treatment assignment will be unblinded once participants are discharged to guide the choice of maintenance therapy for those in the corticosteroid arm. Additionally, participants in the outpatient cohort will be unblinded on Day 5 to facilitate the selection of maintenance therapy for the corticosteroid arm. Following these specified unblinding events, the remainder of the trial, including the post-acute induction and maintenance phases, will be open label with no further blinding.

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: January 16, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)