Upadacitinib for Ulcerative Colitis

(U-ASTOUND Trial)

Recruiting in Palo Alto (17 mi)

+122 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Must not be taking: JAK inhibitors

Disqualifiers: Pregnancy, Breastfeeding, JAK inhibitors, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Ulcerative colitis (UC) is a type of inflammatory bowel disease that causes inflammation and bleeding from the lining of the rectum and colon (large intestine). This study will assess how safe and effective Upadacitinib is in treating pediatric participants with UC. Adverse events and change in disease activity will be assessed. Upadacitinib (RINVOQ) is a drug approved in adults for moderate- to severely active UC and is being developed for moderate- to severely active UC in pediatric participants. This study is conducted in 2 periods: Period 1 is comprised of two phases: an 8-week open-label induction phase which means that the study doctor and patients know that participants will receive UPA Dose-A (or the adult equivalent based on body weight) followed by a 44-week double-blind maintenance phase meaning that neither the participants nor the study doctors will know which dose of upadacitinib will be given(UPA Dose B or Dose C). Period 2 is a 260 week open-label extension (OLE) of Period 1. Approximately 110 pediatric participants with moderate to severely active UC will be enrolled at up to 100 sites worldwide. Participants will receive upadacitinib oral tablets once daily or oral solution twice daily at approximately the same time each day, with or without food. Participants will be followed up for 30 days after each phase (i.e. after induction, maintenance, OLE) and only if a participant doesn't continue into the next phase. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, it mentions that participants should have an inadequate response or intolerance to certain medications like corticosteroids, immunosuppressants, and biologic therapy, which might imply changes to your current treatment. Please consult with the study team for specific guidance.

What data supports the effectiveness of the drug Upadacitinib for treating ulcerative colitis?

Research shows that Upadacitinib, a drug that blocks certain enzymes (JAK inhibitors), is effective in treating ulcerative colitis, helping patients achieve and maintain symptom relief. It has been tested in several studies, including phase 3 trials, where it showed positive results in reducing symptoms and preventing surgery in difficult cases. ^{1 2 3 4 5}

Is upadacitinib safe for humans?

Upadacitinib has been studied for safety in people with ulcerative colitis, showing favorable safety results in several clinical trials. It is an oral medication that works by selectively inhibiting Janus kinase 1, and has been evaluated in both induction and maintenance therapy phases. ^{1 6 7 8 9}

How is the drug Upadacitinib unique for treating ulcerative colitis?

Upadacitinib is unique because it is an oral medication that selectively inhibits Janus kinase 1, providing rapid symptom relief for ulcerative colitis, often as early as the first day of treatment. It is particularly effective for patients with moderate to severe cases and those who have not responded to other treatments, potentially preventing the need for surgery. ^{1 3 4 5 10}

Eligibility Criteria

This trial is for pediatric patients with moderate to severely active Ulcerative Colitis who haven't responded well to other treatments like corticosteroids, immunosuppressants, or biologics. They must have certain levels of disease activity and inflammation in the colon. Pregnant or breastfeeding individuals, or those planning pregnancy during the study period are excluded, as are those previously treated with JAK inhibitors.

Inclusion Criteria

My ulcerative colitis is active with moderate to severe symptoms.

I haven't responded well to standard treatments like steroids, immunosuppressants, or biologics.

Exclusion Criteria

I have been treated with JAK inhibitors before.

I am not pregnant, breastfeeding, nor planning to become pregnant soon.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-Label Induction

Participants receive upadacitinib Dose A for 8 weeks based on body weight

8 weeks

Regular visits at a hospital or clinic

Double-Blind Maintenance

Clinical responders receive either upadacitinib Dose B or Dose C for 44 weeks

44 weeks

Regular visits at a hospital or clinic

Open-Label Long-Term Extension

Participants may continue receiving upadacitinib for up to 260 weeks

260 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Upadacitinib (Janus Kinase (JAK) Inhibitor)

Trial Overview The trial tests Upadacitinib's safety and effectiveness in children with UC over two periods: an initial 8-week phase where everyone knows they're getting the drug followed by a 44-week phase where participants don't know their dose. This leads into a long-term extension for monitoring. The treatment involves daily oral tablets or solution.

Participant Groups

Group I: Period 2- Open Label Long Term Extension Phase Arm B Experimental Treatment 1 Intervention

Clinical non-responders in US after Period 1 induction phase or clinical responders with loss of response during maintenance phase will receive upadacitinib Dose B daily for up to 260 weeks in OLE Period 2.

Group II: Period 2- Open Label Long Term Extension Phase Arm A Experimental Treatment 1 Intervention

Clinical non-responders outside of US after Period 1 induction phase will receive upadacitinib Dose A daily for 8 week extended induction phase in open label long term extension (OLE) Period 2. Clinical responders from extended induction phase in OLE will receive upadacitinib Dose B daily for up to 252 weeks in OLE period 2.

Group III: Period 2- Long Term Extension Phase Arm C Experimental Treatment 1 Intervention

Clinical responders who complete Period 1 through Week 52 will receive upadacitinib Dose C daily for up to 260 weeks in OLE Period 2.

Group IV: Period 1- Open Label Induction Phase Experimental Treatment 1 Intervention

All participants in open label induction phase of Period 1 will receive upadacitinib Dose A for 8 weeks based on body weight.

Group V: Period 1- Double Blind Maintenance Phase Experimental Treatment 1 Intervention

Clinical responders at the end of open label induction phase of Period 1 will be randomly assigned to receive either upadacitinib Dose B or Dose C for 44 weeks based on body weight.

Upadacitinib is already approved in European Union, United States, Canada for the following indications:

🇪🇺 Approved in European Union as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

🇺🇸 Approved in United States as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

🇨🇦 Approved in Canada as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCSF Benioff Children's Hospital Oakland /ID# 255067 Oakland, CA

OSF St. Francis Medical Center /ID# 256968 Peoria, IL

Univ NC Chapel Hill /ID# 254541 Chapel Hill, NC

Alberta Health Services /ID# 252088 Edmonton, Canada

More Trial Locations

Who Is Running the Clinical Trial?

AbbVie Lead Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomised, placebo-controlled, double-blind, phase 3 maintenance study. [2023] Upadacitinib is an oral, selective, and reversible JAK inhibitor with demonstrated efficacy in patients with moderately to severely active ulcerative colitis in a phase 2b induction trial, two phase 3 induction trials (U-ACHIEVE Induction and U-ACCOMPLISH), and a primary analysis of the first 451 patients entering a subsequent maintenance trial (U-ACHIEVE Maintenance). Here, we present overall results from the entire U-ACHIEVE Maintenance population.

2. United States pubmed.ncbi.nlm.nih.gov

In active UC, upadacitinib induced and maintained remission. [2022] Label="SOURCE CITATION">Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399:2113-28. 35644166.

3. England pubmed.ncbi.nlm.nih.gov

Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease. [2023] Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn's disease [CD] in Phase 3 clinical trials.

4. Spain pubmed.ncbi.nlm.nih.gov

Upadacitinib in refractory ulcerative colitis. [2022] We report the first clinical-practice case to date of treatment with upadacitinib for ulcerative colitis, prior refractoriness to all therapeutic options, and preventing proctocolectomy as of today after treatment for 14 months.

5. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. [2023] We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). Post hoc analyses were performed on pooled data from 2 replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH, to determine the earliest time point of efficacy onset.

6. England pubmed.ncbi.nlm.nih.gov

Upadacitinib Induction and Maintenance Therapy Improves Abdominal Pain, Bowel Urgency, and Fatigue in Patients With Ulcerative Colitis: A Post Hoc Analysis of Phase 3 Data. [2023] This post hoc analysis of a large, phase 3 program evaluated the effects of upadacitinib on fatigue, bowel urgency, and abdominal pain in patients with moderately to severely active ulcerative colitis.

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. [2021] We evaluated the efficacy and safety of upadacitinib, an oral selective inhibitor of Janus kinase 1, as induction therapy for ulcerative colitis (UC).

8. England pubmed.ncbi.nlm.nih.gov

Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. [2022] There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.

9. Switzerland pubmed.ncbi.nlm.nih.gov

Upadacitinib Population Pharmacokinetics and Exposure-Response Relationships in Ulcerative Colitis Patients. [2023] Upadacitinib, an oral selective and reversible Janus kinase (JAK) inhibitor, showed favorable efficacy and safety in patients with moderate-to-severe ulcerative colitis (UC). The objective was to characterize upadacitinib pharmacokinetics in UC patients across Phase 2b and 3 trials and evaluate the relationships between upadacitinib plasma exposures and key efficacy or safety endpoints.

10. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience. [2023] Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD.