Upadacitinib for Ulcerative Colitis

(RESCUE UC Trial)

Overseen By Neeraj Narula

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: McMaster University

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Age > 65, Infections, Thrombosis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment method for severe ulcerative colitis (UC) that hasn't improved with standard steroid treatment. It compares the use of a new drug, upadacitinib (a Janus kinase inhibitor), followed by infliximab if needed, to the usual treatment with infliximab alone. Individuals hospitalized with a severe UC flare-up who haven't responded to at least three days of steroid treatment might be suitable candidates. The goal is to determine if this new approach is as effective as the usual treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong CYP3A4 inhibitors or inducers while participating. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that upadacitinib is generally safe for people with ulcerative colitis (UC). Long-term use of this medication has not revealed any new safety concerns. In studies, patients taking upadacitinib did not experience more safety issues than those taking infliximab, a common UC treatment.

Upadacitinib has also proven effective for some patients when other treatments failed, suggesting it could be a viable option for those not responding to standard therapies. While all medications can have side effects, no major unexpected problems have been reported with upadacitinib in UC patients so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Researchers are excited about Upadacitinib for ulcerative colitis because it offers a different approach compared to standard treatments like Infliximab. While many current options target TNF-alpha proteins to reduce inflammation, Upadacitinib is a JAK inhibitor, which means it works by blocking specific enzymes involved in the inflammatory process. This new mechanism of action could potentially provide faster relief and improved outcomes for patients who don't respond well to existing therapies.

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

Research has shown that upadacitinib, which participants in this trial may receive, effectively treats ulcerative colitis (UC). Studies have found that many patients achieve remission, with significant symptom improvement, within 8 to 16 weeks. In everyday use, patients have experienced a noticeable decrease in disease activity and symptoms over time. Upadacitinib has also demonstrated effectiveness comparable to infliximab, the standard care treatment arm in this trial, for hospitalized patients. Overall, this treatment offers a good balance of benefits and risks for people with moderate to severe UC over several years. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for hospitalized patients with a confirmed diagnosis of acute severe ulcerative colitis who haven't improved after at least three days on IV steroids. Participants must have had recent colonoscopy or sigmoidoscopy, be able to follow study procedures, and provide written consent.

Inclusion Criteria

Provided written informed consent

Subject is willing and able to adhere to study procedures

I am an adult under 65 with ulcerative colitis and not pregnant or breastfeeding.

Exclusion Criteria

I am older than 65.

I have active tuberculosis.

HBV/HCV positive

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Upadacitinib 45mg daily for at least five days, followed by infliximab in non-responders, or standard care with infliximab

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib

Trial Overview The study tests if using upadacitinib first, then infliximab for non-responders, is as effective as the standard treatment with infliximab alone in patients with steroid-refractory acute severe ulcerative colitis.

How Is the Trial Designed?

Group I: Infliximab (standard care) Active Control 1 Intervention

Participants will receive standard care, which is Infliximab.

Group II: Upadacitinib (treatment arm) Active Control 1 Intervention

Participants will receive Upadacitinib 45mg daily, once a day, for at least five days.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

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. 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.

2. 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 ...

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. journals.lww.com journals.lww.com/ajg/fulltext/2024/10001/s1387_real_world_efficacy_and_safety_outcomes.1388.aspx

S1387 Real World Efficacy and Safety Outcomes Analysis ... Upadacitinib demonstrates comparable efficacy & safety to infliximab in real-world hospitalized UC patients. While there was no significant difference observed ...

5. cghjournal.org cghjournal.org/article/S1542-3565(25)00639-1/fulltext

Comparative effectiveness of tofacitinib versus upadacitinib ... Upadacitinib showed higher early response rates, but long-term outcomes were comparable for both. Implications for patient care. Tofacitinib and ...

6. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(25)00017-2/fulltext

Long-term efficacy and safety of upadacitinib in patients ... The U-ACTIVATE long-term extension study aims to evaluate the long-term efficacy and safety of upadacitinib in patients with moderately to severely active ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40217680/

Real-World Effectiveness and Safety of Upadacitinib in ... Steroid-free remission was achieved in 39% of patients at week 8. Upadacitinib results were unaffected by prior biologic or JAKi failure. Mean ...

8. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i84/7967017

DOP002 Efficacy and safety of upadacitinib after 4 years of ... The long-term safety profile for UPA in pts with UC was consistent with previous analyses,1,2 with no new safety risks identified in the ongoing ...

9. mdpi.com mdpi.com/2077-0383/14/21/7801

or Third-Line Therapy in Patients with Ulcerative Colitis The clinical remission and clinical response rates were 45.5% (92/202) and 63.5% (128/202), respectively, at 8 weeks and 60.2% and 81.7%, respectively, at the ...