Upadacitinib + Corticosteroids for Ulcerative Colitis Flare-Up

(ACUTE Trial)

Overseen By Queen Saunyama

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Berinstein, Jeffrey

Must be taking: Corticosteroids

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Active infection, Pregnancy, Liver cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best way to use medications for treating severe flare-ups of ulcerative colitis, a chronic inflammation of the colon. Researchers compare the effectiveness of the drug upadacitinib, an oral medication, combined with corticosteroids to corticosteroids alone. Participants are either hospitalized or treated as outpatients, with some receiving both drugs and others receiving a placebo instead of upadacitinib. This trial may suit individuals who have experienced at least six bloody bowel movements daily for the past week and have recently used oral corticosteroids. As a Phase 4 trial, this research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

What is the safety track record for these treatments?

Research has shown that upadacitinib, also known as RINVOQ, has been thoroughly studied for treating moderate to severe ulcerative colitis. The FDA has already approved it for this condition, indicating general safety. However, like many medications, it can cause side effects. Studies indicate that patients might experience infections, and some may develop acne. Specifically, in one study with 105 patients, about 32% reported side effects, with 23% experiencing acne.

Corticosteroids are also commonly used to treat inflammation and are usually well-tolerated. They can cause side effects like increased appetite, mood changes, or trouble sleeping, but these are typically manageable.

Overall, while both treatments can have side effects, they are considered safe for treating ulcerative colitis. Always consult a doctor about the potential risks and benefits specific to your health. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about upadacitinib in combination with corticosteroids for ulcerative colitis because it offers a novel approach by targeting the Janus kinase (JAK) pathway, which plays a key role in the immune response and inflammation. Unlike traditional treatments that primarily focus on broad immune suppression, upadacitinib provides more targeted action, potentially leading to faster symptom relief and improved outcomes. Additionally, the flexibility in dosing based on clinical symptoms and biomarkers allows for personalized treatment, which could enhance its effectiveness and safety compared to standard therapies.

What evidence suggests that this trial's treatments could be effective for acute severe ulcerative colitis?

Research has shown that upadacitinib effectively treats ulcerative colitis. Studies found that many patients experienced fewer symptoms after 8 and 16 weeks. Over the long term, upadacitinib remained effective and safe, helping patients manage their condition for up to three years. This trial will evaluate upadacitinib in combination with corticosteroids for ulcerative colitis flare-ups. Participants in one arm will receive upadacitinib plus steroids, while another arm will receive steroids plus a placebo for upadacitinib. This medication also quickly reduces the activity and severity of the disease, providing fast symptom relief. Based on this evidence, upadacitinib is considered a promising treatment option for ulcerative colitis. ^{6 7 8 9 10}

Who Is on the Research Team?

Jeffrey Berinstein, MD, MSc

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for both inpatients and outpatients with acute severe ulcerative colitis (ASUC) experiencing a flare-up. Participants must meet specific health criteria to join, but the exact inclusion and exclusion details are not provided here.

Inclusion Criteria

Intent to use effective birth control for individuals of reproductive potential

Participants in the outpatient cohort must be under the care of an outpatient gastroenterologist affiliated with the University of Michigan

Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, daily bowel movement symptoms surveys, and other study procedures

Exclusion Criteria

History of clinically significant drug or alcohol abuse within the last 6 months

History of multiple episodes of herpes zoster or disseminated herpes zoster

Known hypersensitivity to specific drugs or constituents

Timeline for a Trial Participant

Eligibility Assessment

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Induction

Participants receive upadacitinib and corticosteroids or corticosteroids alone as induction therapy

0-10 days (inpatient), 5 days (outpatient)

Post-Acute Induction

Participants continue treatment with upadacitinib and taper prednisone for 8 weeks

8 weeks

Maintenance

Upadacitinib therapy may continue with dosage titration based on clinical symptoms and inflammatory biomarkers

Week 8 to Week 48

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intravenous Methylprednisolone
• Oral prednisolone Taper
• Oral Upadacitinib

Trial Overview The study compares the effectiveness of combining Upadacitinib with corticosteroids versus using corticosteroids alone as initial treatment for ASUC. It aims to determine which method works better early on.

How Is the Trial Designed?

Group I: Upadacitinib plus steroids-Outpatient cohort Experimental Treatment 4 Interventions

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.

Group II: Upadacitinib plus steroids- Inpatient cohort Experimental Treatment 3 Interventions

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.

Group III: Steroids plus Upadacitinib Placebo- Inpatient cohort Active Control 3 Interventions

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.

Group IV: Steroids plus Upadacitinib Placebo-Outpatient cohort Active Control 4 Interventions

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.

Who Is Running the Clinical Trial?

Berinstein, Jeffrey

Lead Sponsor

Trials

1

Recruited

160+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Citations

1. rinvoqhcp.com rinvoqhcp.com/ulcerative-colitis/efficacy

RINVOQ® (upadacitinib) Efficacy for Ulcerative Colitis UC EFFICACY RESULTS · Durable Remission · Powerful Healing · Rapid Relief · Durable Remission. at Week 8 and 52 · Powerful Healing. at Weeks 8 and 52 · Rapid Relief.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39709985/

Upadacitinib induction is effective and safe in ulcerative ... Upadacitinib resulted in high rates of clinical remission at 8 and 16 weeks in this large real-world cohort of ulcerative colitis patients.

3. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1260/7968004

P0642 Assessment of the real-world effectiveness of ... In a real-world global setting, UPA demonstrated significant efficacy in reducing disease activity, severity and UC-related symptoms over time.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2468125325000172

Long-term efficacy and safety of upadacitinib in patients ... Our findings show a favourable risk–benefit profile of upadacitinib in patients with moderately to severely active ulcerative colitis through 3 years of ...

5. rinvoq.com rinvoq.com/ulcerative-colitis/about-rinvoq/rinvoq-results

RINVOQ® (upadacitinib) Results for Ulcerative Colitis (UC) In clinical studies, RINVOQ helped people with UC experience remission at 8 weeks and 1 year. RINVOQ also helped deliver: Rapid symptom ...

6. rinvoqhcp.com rinvoqhcp.com/dermatology/safety

RINVOQ® (upadacitinib) Safety Data Long-term safety data through November 24, 2020 (64%-66% of patients had >1 year of exposure to RINVOQ; total exposure=2788 PY).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/211675s015lbl.pdf

RINVOQ® (upadacitinib) - accessdata.fda.gov RINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance ...

8. rinvoq.com rinvoq.com/ulcerative-colitis

RINVOQ® (upadacitinib) for Ulcerative Colitis (UC) Learn about a prescription treatment for adults with moderate to severe ulcerative colitis (UC). See Full Prescribing & Safety Info, and Boxed Warning.

9. rinvoqhcp.com rinvoqhcp.com/gastroenterology/safety

well-studied safety profile Patients treated with RINVOQ are at increased risk for developing infections that may lead to hospitalization or death.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11016252/

(CGH-D-22-02573) Upadacitinib is Effective and Safe in ... Table 4: Safety data of upadacitinib in ulcerative colitis and Crohn's disease patients. N = 105. Adverse effects – n (%), 34 (32.4). Acne – n (%), 24 (22.9).