Upadacitinib for Ulcerative Colitis

(U-ASTOUND Trial)

Recruiting at 123 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: JAK inhibitors

Disqualifiers: Pregnancy, Breastfeeding, JAK inhibitors, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

110 Participants Needed

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}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

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.

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

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

Who Is Running the Clinical Trial?

AbbVie

Lead 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

Findings from Research

In a phase 3 maintenance study involving 681 patients with moderately to severely active ulcerative colitis, upadacitinib at doses of 15 mg and 30 mg once daily significantly improved clinical remission rates compared to placebo, with 40.4% and 53.6% of patients achieving remission, respectively.

The safety profile of upadacitinib showed some increased risks for specific adverse events, such as herpes zoster and hepatic disorders, but overall, it demonstrated a positive benefit-risk profile, making it a promising treatment option for patients with ulcerative colitis.

NCBI (Pubmed)

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. Vermeire, S., Danese, S., Zhou, W., et al.[2023]

Upadacitinib has been shown to be effective as both an induction and maintenance therapy for patients with moderately to severely active ulcerative colitis, based on results from three phase 3 clinical trials.

The trials demonstrated significant improvements in clinical remission rates and symptom control, highlighting upadacitinib's potential as a valuable treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In active UC, upadacitinib induced and maintained remission. Forbes, GM.[2022]

In a real-world study of 45 patients with moderate to severe Crohn's disease treated with upadacitinib, 63.6% achieved a clinical response and 27.2% achieved clinical remission after 3 months, indicating its efficacy in managing the disease.

The safety profile of upadacitinib was acceptable, with 26.7% of patients experiencing adverse events, and only 4.5% having serious adverse events without any reported mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease. Chugh, R., Braga-Neto, MB., Fredrick, TW., et al.[2023]

This case study presents the first clinical use of upadacitinib for a patient with ulcerative colitis who had previously not responded to any other treatments, highlighting its potential as a new therapeutic option.

After 14 months of treatment with upadacitinib, the patient has successfully avoided proctocolectomy, suggesting that this medication can effectively manage severe cases of ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib in refractory ulcerative colitis. Rodríguez Toboso, G., Rivera Vaquerizo, PÁ., Martínez López, MN., et al.[2022]

In a study involving 988 patients, upadacitinib 45 mg once daily showed significant early improvements in ulcerative colitis symptoms, with effects noticeable as early as day 1 and maintained through day 14, compared to placebo.

The treatment led to a substantial reduction in inflammatory markers, with over 75% of patients achieving a greater than 50% reduction in hs-CRP levels, and it was associated with higher rates of clinical remission and improved quality of life at weeks 2 and 8.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. Loftus, EV., Colombel, JF., Takeuchi, K., et al.[2023]

In a large phase 3 study involving patients with moderately to severely active ulcerative colitis, upadacitinib significantly reduced abdominal pain and bowel urgency starting from week 2, compared to placebo (P < .001).

Patients treated with upadacitinib also experienced meaningful improvements in fatigue scores at week 8, and these benefits were sustained over 52 weeks of maintenance treatment, indicating its long-term efficacy.

NCBI (Pubmed)

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. Danese, S., Tran, J., D'Haens, G., et al.[2023]

In a phase 2b trial involving 250 adults with moderately to severely active ulcerative colitis, upadacitinib showed significant efficacy in inducing clinical remission compared to placebo, with remission rates increasing with higher doses (up to 19.6% at 45 mg).

While upadacitinib was effective, there were safety concerns, including reported cases of herpes zoster and thromboembolic events, as well as increases in serum lipid levels and creatine phosphokinase, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. Sandborn, WJ., Ghosh, S., Panes, J., et al.[2021]

In a phase 3 clinical trial involving 474 patients, upadacitinib (45 mg once daily) significantly improved clinical remission rates in patients with moderately to severely active ulcerative colitis compared to placebo, with 26% and 34% of patients achieving remission in two separate studies (p<0.0001).

The safety profile of upadacitinib was favorable, with fewer serious adverse events and treatment discontinuations compared to placebo, indicating it is a potentially effective and safe treatment option for ulcerative colitis.

NCBI (Pubmed)

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. Danese, S., Vermeire, S., Zhou, W., et al.[2022]

Upadacitinib, a JAK inhibitor, demonstrated dose-proportional pharmacokinetics in 1234 ulcerative colitis patients across Phase 2 and 3 trials, showing maximized efficacy at the 45 mg daily dose during the 8-week induction phase.

The 30 mg daily maintenance dose provided additional benefits over the 15 mg dose for long-term clinical outcomes, with no safety concerns linked to increased plasma exposure, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Population Pharmacokinetics and Exposure-Response Relationships in Ulcerative Colitis Patients. Ponce-Bobadilla, AV., Stodtmann, S., Eckert, D., et al.[2023]

In a study of 105 patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), upadacitinib demonstrated rapid efficacy, with 85.2% of UC patients achieving clinical response by 8 weeks, and 70.6% of CD patients achieving clinical remission.

Upadacitinib was found to be safe, with acne being the most common adverse event reported in 22.9% of patients, and it was effective even in patients who had previously been treated with other therapies like tofacitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience. Friedberg, S., Choi, D., Hunold, T., et al.[2023]

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]

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

In active UC, upadacitinib induced and maintained remission. [2022]

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

Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease. [2023]

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

Upadacitinib in refractory ulcerative colitis. [2022]

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

Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. [2023]

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]

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

Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. [2021]

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]

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

Upadacitinib Population Pharmacokinetics and Exposure-Response Relationships in Ulcerative Colitis Patients. [2023]

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]