Ulcerative Colitis AcutePhase 4ACUTENCT07258771
Upadacitinib Combined With Corticosteroids vs Corticosteroid Monotherapy Induction for Inpatients and Outpatients With Acute Severe Ulcerative Colitis
A Phase 4 study testing Oral Upadacitinib, Intravenous Methylprednisolone and Oral prednisolone Taper in people with Ulcerative Colitis Acute, run by Berinstein, Jeffrey at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis Acute
- What is being tested?
- Oral Upadacitinib, Intravenous Methylprednisolone and Oral prednisolone Taper
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2026to Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Temperature > 37.8 Celsius(C) per patient report or documented in Electronic Health Record (EHR) in the 7 days prior to Day 0.
- 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.
- Oral corticosteroid use for ≥ 7 days in the month prior to consent at a dose equivalent to ≥ 20 milligrams per day (mg/day)
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- 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.
Who cannot join
- 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.
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- 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 with active Cytomegalovirus (CMV) colitis as defined as having > 5 CMV inclusion bodies per high powered field in any one ulcer at baseline. If CMV colitis is confirmed, the patient can remain in the trial if permissible by the infectious disease and primary treatment team and if concomitant anti-viral therapy is initiated.
- 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)
- Patients with certain laboratory abnormalities suggestive of moderate or severe renal, hematological, or gastrointestinal/liver impairment (per protocol).
- History of or clinical evidence of liver cirrhosis
- History of inherited or acquired conditions that predispose to hypercoagulability (per protocol). Please note, that patients with a remote history of provoked thromboembolic event or recent thromboembolic event on systemic anticoagulation are NOT exclusionary.
- Active Hepatitis B Infection: Hepatitis B surface antigen (HBsAg) positive with detectable deoxyribonucleic acid (DNA) not on therapy. Patients with serologic evidence of a resolved prior hepatitis B virus (HBV) infection (i.e., HBsAg-negative and anti-HB Core-positive) or patients with HBsAg positive on suppressive HBV therapy with low DNA (<105 copies/milliliter (mL) or <104 IU/mL negative) are not exclusionary.
- Active Hepatitis C Infection: Hepatitis C Virus (HCV) ribonucleic acid detectable in any patient with anti-HCV antibody.
- Acquired Immunodeficiency Syndrome: Confirmed positive anti-human immunodeficiency virus (HIV) antibody with cluster of differentiation 4 (CD4) counts <350 cells/microliter (uL) or Acquired Immune Deficiency Syndrome (AIDS)- defining opportunist infection.
- Solid organ or bone marrow transplant within 1 year or expected transplant within 6 months of randomization.
- Patients that had a history of spontaneous GI perforation (other than appendicitis or mechanical injury) or are at significantly increased risk of GI perforation per investigator's judgment.
- Actively receiving strong CYP3A4 inducers or inhibitors prior to the first dose of study drug or are expected to receive any of these medications during the study period. This includes grapefruit and grapefruit juice.
- The presence of any condition possibly affecting oral drug absorption (e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery) as determined by the investigator. Procedures such as gastric banding that simply divide the stomach into separate chambers are not exclusionary.
- Patients that had a history of a clinically significant medical condition per protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Syed Hassan, 734-232-5134, hasyed@umich.edu
Jeffrey Berinstein, MD, MSc
About this study
Official title: Acute Severe Ulcerative Colitis- Upadacitinib Combined With Corticosteroids vs Corticosteroid Monotherapy Induction While Transitioning Away From the Emergency Setting (ACUTE): A Phase IV, Single Center, Partially Blinded, Randomized Study
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.
Read the detailed description
This study will have four phases: eligibility assessment, the acute induction phase (inpatient 0-10 days, outpatient 5 days), post-acute induction phase (end of acute induction phase to day 56 (week 8)), and maintenance phase (week 8-week 48).
- Conditions
- Ulcerative Colitis Acute
- Being tested
- Oral Upadacitinib, Intravenous Methylprednisolone, Oral Upadacitinib Placebo, Oral prednisolone Taper, Oral Prednisone - Hospital Dose Steroids
- Keywords
- Acute Severe Ulcerative Colitis, Inpatient, Outpatient, Optimal sequence, Upadacitinib, Corticosteroids
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral UpadacitinibDrug
Also called Rinvoq
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.
Intravenous MethylprednisoloneDrug
Also called Solumedrol
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.
Oral Upadacitinib PlaceboDrug
Also called Placebo
The placebo will be discontinued at discharge for the inpatient cohort and after day 5 for the outpatient cohort.
Oral prednisolone TaperDrug
Also called Prednisone
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).
Oral Prednisone - Hospital Dose SteroidsDrug
Also called prednisone
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Intravenous Methylprednisolone; Drug: Oral Upadacitinib Placebo; Drug: Oral prednisolone Taper |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Clinical response is defined by having a C-reactive protein (CRP) <0.8 mg/dL AND ≤ 4 liquid bowel movements per 24 hours and no more than trace blood in stool.
Measured: Week 8 (day 56)
The proportion of participants in clinical response without colectomy or rescue therapy by week 12/Day 84 in the upadacitinib and corticosteroid arm compared corticosteroid monotherapy arm
Clinical response is defined by having a C-reactive protein (CRP) <0.8 mg/dL AND ≤ 4 liquid bowel movements per 24 hours and no more than trace blood in stool.
Measured: Week 12 (Day 84)
The proportion of participants in clinical response without colectomy or rescue therapy by week 48/Day 336 in the upadacitinib and corticosteroid arm compared corticosteroid monotherapy arm
Clinical response is defined by having a C-reactive protein (CRP) <0.8 mg/dL AND ≤ 4 liquid bowel movements per 24 hours and no more than trace blood in stool.
Measured: Week 48 (Day 336)
The proportion of participants in corticosteroid-free clinical remission without colectomy or rescue therapy by week 8/Day 56 in the upadacitinib and corticosteroid compared to corticosteroid monotherapy arm
Clinical remission is defined as having ≤ 2 liquid bowel movements per 24 hours and having visible rectal bleeding score of 0. Corticosteroid-free clinical remission is defined as being in clinical remission without the use of corticosteroids ≥ 14 days prior to time-point
Measured: Week 8 (Day 56)
The proportion of participants in corticosteroid-free clinical remission without colectomy or rescue therapy by week 12/Day 84 in the upadacitinib and corticosteroid compared to corticosteroid monotherapy arm
Clinical remission is defined as having ≤ 2 liquid bowel movements per 24 hours and having visible rectal bleeding score of 0. Corticosteroid-free clinical remission is defined as being in clinical remission without the use of corticosteroids ≥ 14 days prior to time-point
Measured: Week 12 (Day 84)
The proportion of participants in corticosteroid-free clinical remission without colectomy or rescue therapy by week 48/Day 336 in the upadacitinib and corticosteroid compared to corticosteroid monotherapy arm
Clinical remission is defined as having ≤ 2 liquid bowel movements per 24 hours and having visible rectal bleeding score of 0. Corticosteroid-free clinical remission is defined as being in clinical remission without the use of corticosteroids ≥ 14 days prior to time-point
Measured: Week 48 (Day 336)
Incidence and severity of adverse events by end of the Acute Induction Phase (Inpatient Cohort: 0-10 days; Outpatient Cohort: 5 days)
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: End of the acute induction phase (0-10 days) in the safety population
Incidence and severity of adverse events by the end of the post-acute induction phase (week 8/Day 56)
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Post-acute induction phase (week 8/Day 56) in the safety population
Incidence and severity of adverse events by week 12/Day 84
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 12 (Day 84) in the safety population
Incidence and severity of adverse events by week 52/Day 365 (Study period + 4-week safety follow-up period) in the safety population
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 52 (Day 365) in the safety population
Incidence of serious infections by end of the acute induction phase (0-10 days)
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Acute induction phase (0-10 days) in the safety population
Incidence of serious infections by post-acute induction phase week 8/Day 56
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 8 (Day 56) in the safety population
Incidence of serious infections by end of week 12/Day 84
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 12 (Day 84) in the safety population
Incidence of serious infections by Week 52/Day 365 (Study Period + 4-week Safety Follow-up)
Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 52 (Day 365) in the safety population
Incidence and severity of adverse events of special interest (AESI) by end of the acute induction phase (0-10 days)
Adverse events of special interest include serious infections, opportunistic infections, herpes zoster, active TB, malignancy (all types), adjudicated gastrointestinal perforations, adjudicated cardiovascular events (e.g., major adverse cardiac event (MACE)), anemia, neutropenia, lymphopenia, renal dysfunction, hepatic disorder, adjudicated embolic and thrombotic events (non-cardiac, non-central nervous system), serious hypersensitivity reactions, bone fracture, and retinal detachment. Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Acute induction phase (0-10 days) in the safety population
Incidence and severity of adverse events of special interest by week 8/Day 56
Adverse events of special interest include serious infections, opportunistic infections, herpes zoster, active TB, malignancy (all types), adjudicated gastrointestinal perforations, adjudicated cardiovascular events (e.g., major adverse cardiac event (MACE)), anemia, neutropenia, lymphopenia, renal dysfunction, hepatic disorder, adjudicated embolic and thrombotic events (non-cardiac, non-central nervous system), serious hypersensitivity reactions, bone fracture, and retinal detachment. Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 8 (Day 56) in the safety population
Incidence and severity of adverse events of special interest by week 12/Day 84
Adverse events of special interest include serious infections, opportunistic infections, herpes zoster, active TB, malignancy (all types), adjudicated gastrointestinal perforations, adjudicated cardiovascular events (e.g., major adverse cardiac event (MACE)), anemia, neutropenia, lymphopenia, renal dysfunction, hepatic disorder, adjudicated embolic and thrombotic events (non-cardiac, non-central nervous system), serious hypersensitivity reactions, bone fracture, and retinal detachment. Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 12 (Day 84) in the safety population.
Incidence and severity of adverse events of special interest for by week 52/Day 365 (Study period + 4-week Safety Follow-up Period) in the safety population
Adverse events of special interest include serious infections, opportunistic infections, herpes zoster, active TB, malignancy (all types), adjudicated gastrointestinal perforations, adjudicated cardiovascular events (e.g., major adverse cardiac event (MACE)), anemia, neutropenia, lymphopenia, renal dysfunction, hepatic disorder, adjudicated embolic and thrombotic events (non-cardiac, non-central nervous system), serious hypersensitivity reactions, bone fracture, and retinal detachment. Adverse events will be graded to the 5 criteria as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Safety population includes all participants that received at least one dose of study drug
Measured: Week 52 (Day 365) in the safety population.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start16 Jan 2026
- Primary completionDec 2029 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative Colitis AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Berinstein, Jeffrey
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor-investigator, Berinstein, Jeffrey, University of Michigan
- Investigators
- Jeffrey Berinstein, MD, MSc, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07258771
- Sponsor's protocol ID
- HUM00266952
- Acronym
- ACUTE
- Status last verified
- Jan 2026
- First submitted
- 20 Nov 2025
- Last updated
- 2 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Severe Ulcerative Colitis- Upadacitinib Combined With Corticosteroids vs Corticosteroid Monotherapy Induction While Transitioning Away From the Emergency Setting (ACUTE): A Phase IV, Single Center, Partially Blinded, Randomized Study
- ClinicalTrials.gov ID
- NCT07258771
- Acronym / sponsor ID
- ACUTE / HUM00266952
- Conditions
- Ulcerative Colitis Acute
- Keywords
- Acute Severe Ulcerative Colitis, Inpatient, Outpatient, Optimal sequence, Upadacitinib, Corticosteroids
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Berinstein, JeffreyUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- 16 Jan 2026 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will have four phases: eligibility assessment, the acute induction phase (inpatient 0-10 days, outpatient 5 days), post-acute induction phase (end of acute induction phase to day 56 (week 8)), and maintenance phase (week 8-week 48).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Upadacitinib plus steroids-Outpatient cohort | Experimental | Drug: Oral Upadacitinib, Drug: Intravenous Methylprednisolone, Drug: Oral prednisolone Taper, Drug: Oral Prednisone - Hospital Dose SteroidsThis 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. |
| Steroids plus Upadacitinib Placebo-Outpatient cohort | Active comparator | Drug: Intravenous Methylprednisolone, Drug: Oral Upadacitinib Placebo, Drug: Oral prednisolone Taper, Drug: Oral Prednisone - Hospital Dose SteroidsThis 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. |
| Upadacitinib plus steroids- Inpatient cohort | Experimental | Drug: Oral Upadacitinib, Drug: Intravenous Methylprednisolone, Drug: Oral prednisolone TaperThis 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. |
| Steroids plus Upadacitinib Placebo- Inpatient cohort | Active comparator | Drug: Intravenous Methylprednisolone, Drug: Oral Upadacitinib Placebo, Drug: Oral prednisolone TaperThis 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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.
- Oral corticosteroid use for ≥ 7 days in the month prior to consent at a dose equivalent to ≥ 20 milligrams per day (mg/day)
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral UpadacitinibAlso: RinvoqDoses 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. | Drug | Upadacitinib plus steroids- Inpatient cohort, Upadacitinib plus steroids-Outpatient cohort |
| Intravenous MethylprednisoloneAlso: SolumedrolIntravenous (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. | Drug | Steroids plus Upadacitinib Placebo- Inpatient cohort, Steroids plus Upadacitinib Placebo-Outpatient cohort, Upadacitinib plus steroids- Inpatient cohort, Upadacitinib plus steroids-Outpatient cohort |
| Oral Upadacitinib PlaceboAlso: PlaceboThe placebo will be discontinued at discharge for the inpatient cohort and after day 5 for the outpatient cohort. | Drug | Steroids plus Upadacitinib Placebo- Inpatient cohort, Steroids plus Upadacitinib Placebo-Outpatient cohort |
| Oral prednisolone TaperAlso: PrednisoneFollowing 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). | Drug | 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 SteroidsAlso: prednisoneOral 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. | Drug | Steroids plus Upadacitinib Placebo-Outpatient cohort, Upadacitinib plus steroids-Outpatient cohort |
Primary outcome
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
Time frame: Treatment 5 days
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.
22 secondary outcomes
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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 8 (day 56)
The proportion of participants in clinical response without colectomy or rescue therapy by week 12/Day 84 in the upadacitinib and corticosteroid arm compared corticosteroid monotherapy arm
Time frame: Week 12 (Day 84)
The proportion of participants in clinical response without colectomy or rescue therapy by week 48/Day 336 in the upadacitinib and corticosteroid arm compared corticosteroid monotherapy arm
Time frame: Week 48 (Day 336)
The proportion of participants in corticosteroid-free clinical remission without colectomy or rescue therapy by week 8/Day 56 in the upadacitinib and corticosteroid compared to corticosteroid monotherapy arm
Time frame: Week 8 (Day 56)
The proportion of participants in corticosteroid-free clinical remission without colectomy or rescue therapy by week 12/Day 84 in the upadacitinib and corticosteroid compared to corticosteroid monotherapy arm
Time frame: Week 12 (Day 84)
The proportion of participants in corticosteroid-free clinical remission without colectomy or rescue therapy by week 48/Day 336 in the upadacitinib and corticosteroid compared to corticosteroid monotherapy arm
Time frame: Week 48 (Day 336)
Incidence and severity of adverse events by end of the Acute Induction Phase (Inpatient Cohort: 0-10 days; Outpatient Cohort: 5 days)
Time frame: End of the acute induction phase (0-10 days) in the safety population
Incidence and severity of adverse events by the end of the post-acute induction phase (week 8/Day 56)
Time frame: Post-acute induction phase (week 8/Day 56) in the safety population
Incidence and severity of adverse events by week 12/Day 84
Time frame: Week 12 (Day 84) in the safety population
Incidence and severity of adverse events by week 52/Day 365 (Study period + 4-week safety follow-up period) in the safety population
Time frame: Week 52 (Day 365) in the safety population
Incidence of serious infections by end of the acute induction phase (0-10 days)
Time frame: Acute induction phase (0-10 days) in the safety population
Incidence of serious infections by post-acute induction phase week 8/Day 56
Time frame: Week 8 (Day 56) in the safety population
Incidence of serious infections by end of week 12/Day 84
Time frame: Week 12 (Day 84) in the safety population
Incidence of serious infections by Week 52/Day 365 (Study Period + 4-week Safety Follow-up)
Time frame: Week 52 (Day 365) in the safety population
Incidence and severity of adverse events of special interest (AESI) by end of the acute induction phase (0-10 days)
Time frame: Acute induction phase (0-10 days) in the safety population
Incidence and severity of adverse events of special interest by week 8/Day 56
Time frame: Week 8 (Day 56) in the safety population
Incidence and severity of adverse events of special interest by week 12/Day 84
Time frame: Week 12 (Day 84) in the safety population.
Incidence and severity of adverse events of special interest for by week 52/Day 365 (Study period + 4-week Safety Follow-up Period) in the safety population
Time frame: Week 52 (Day 365) in the safety population.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jeffrey Berinstein, MD, MSc principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral Upadacitinib, Intravenous Methylprednisolone and Oral prednisolone Taper in people with Ulcerative Colitis Acute, run by Berinstein, Jeffrey at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Queen Saunyama (734-647-2564, saunayma@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Treatment 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2026.