Upadacitinib for Crohn's Disease

(U-EMPOWER Trial)

Recruiting at 109 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Disqualifiers: Ulcerative colitis, Abscess, Bowel strictures, 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: 1

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called upadacitinib, a Janus kinase inhibitor, for children and teens with moderate to severe Crohn's disease. The researchers aim to determine if the medication is safe and effective for those who haven't succeeded with treatments like steroids or biologic therapy. Participants will receive the medication in two phases: a 12-week open phase where everyone knows they are receiving the drug, followed by a 52-week phase where the exact dose remains unknown to all. Children aged 2 to 18 with Crohn's disease, who experience symptoms like abdominal pain and diarrhea despite previous treatments, might be suitable for this trial. Participants must attend regular clinic visits for check-ups and assessments throughout the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study doctor to understand how your current treatments might interact with the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that upadacitinib is generally safe for adults with moderate to severe Crohn's disease. In several studies, most patients did not experience serious side effects. One study found that 52.1% of patients experienced significant symptom improvement, with the disease becoming inactive after 12 weeks, demonstrating the drug's effectiveness and manageable side effects. Another study showed that upadacitinib was more effective than a placebo, providing benefits without major issues.

Although these studies involved adults, they offer some insight into the drug's safety. The FDA has already approved upadacitinib for adults, suggesting it manages side effects well. However, since this trial involves children, ongoing safety monitoring in this age group remains crucial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Crohn's Disease?

Most treatments for Crohn's disease, like biologics and corticosteroids, focus on controlling inflammation through broad immune suppression. However, upadacitinib is different because it is a JAK inhibitor, which means it targets specific pathways responsible for inflammation, potentially reducing side effects associated with broader immune suppression. Researchers are excited about upadacitinib because its targeted approach could offer more precise control of inflammation, leading to better management of symptoms and improving the quality of life for patients with Crohn's disease. Additionally, its oral administration makes it a convenient alternative to injectable treatments, enhancing patient compliance.

What evidence suggests that upadacitinib might be an effective treatment for Crohn's disease?

Research has shown that upadacitinib effectively treats moderate-to-severe Crohn's disease. In this trial, participants will receive different doses of upadacitinib across various phases. Specifically, studies found that 52.1% of patients experienced symptom relief after 12 weeks of using upadacitinib. Additionally, 42.7% of patients showed healing in their digestive tract after six months of treatment. This medication has proven effective even for those who did not find relief with other treatments. Overall, upadacitinib shows promising results for managing Crohn's disease symptoms. ^{2 4 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for children aged 2-18 with moderate to severe Crohn's Disease who haven't had success with, or can't use, standard treatments like corticosteroids and biologics. They must weigh at least 10 kg and have a confirmed diagnosis of CD with specific endoscopic findings.

Inclusion Criteria

Weight at Screening and Baseline must be ≥ 10 kg

My Crohn's disease is moderate to severe with a PCDAI score over 30 and confirmed inflammation.

My condition didn't improve or worsened with standard treatments, or I can't tolerate them.

Exclusion Criteria

I do not have conditions like short bowel syndrome or have had gastric bypass surgery that could affect drug absorption.

Japan participants only: positive result of beta-D-glucan or two consecutive indeterminate results of beta-D-glucan during the Screening period (screening for Pneumocystis jiroveci infection)

I was diagnosed with CD before I turned 2 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-Label Induction

Participants receive upadacitinib Dose A for 12 weeks based on body weight

12 weeks

Weekly visits (in-person)

Double-Blind Maintenance

Participants receive either upadacitinib Dose B or Dose C for 52 weeks

52 weeks

Monthly visits (in-person)

Open-Label Long-Term Extension

Participants continue to receive upadacitinib for up to 156 weeks

156 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib

Trial Overview The trial tests Upadacitinib's safety and effectiveness in these kids over two periods: first a known-dose phase for 12 weeks, then a year where the dose is unknown to them. It ends with an open-label extension for up to three years.

How Is the Trial Designed?

Group I: Period 2: Open Label Long-Term Extension Phase Cohort 3 Experimental Treatment 1 Intervention

Participants who did not achieve clinical response per PCDAI at Week 12 of Period 1 will receive an extended treatment with open-label upadacitinib Dose C daily for an additional 12 weeks. If they are responders after 12 weeks extended treatment, they will continue, otherwise they may be discontinued at the discretion of the investigator

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

Participants who were receiving rescue therapy with open-label upadacitinib Dose C during maintenance phase in Period 1 and completed the Week 64 visit will continue to receive upadacitinib Dose C daily for up to 156 weeks.

Group III: Period 2: Open Label Long-Term Extension Phase Cohort 1 Experimental Treatment 1 Intervention

Participants receiving double-blind maintenance therapy with upadacitinib Dose B or upadacitinib Dose C daily in Period 1 who complete the Week 64 visit will receive upadacitinib Dose B daily for up to 156 weeks.

Group IV: Period 1: Open Label Induction Phase (Dose A) Experimental Treatment 1 Intervention

All participants in the open label induction phase of Period 1 will receive upadacitinib Dose A for 12 weeks based on body weight.

Group V: Period 1: Double-Blind Maintenance Phase (Dose C) Experimental Treatment 1 Intervention

Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive either upadacitinib Dose C or B for 52 weeks (oral solution dose will be based on body weight)

Group VI: Period 1: Double-Blind Maintenance Phase (Dose B) Experimental Treatment 1 Intervention

Clinical responders per PCDAI at the end of open label induction phase of Period 1 will be randomly assigned to receive Dose B or C for 52 weeks (oral solution dose will be 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

Published Research Related to This Trial

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]

In two phase 3 trials involving over 1,500 patients with moderate-to-severe Crohn's disease, upadacitinib (45 mg) significantly improved clinical remission and endoscopic response compared to placebo after 12 weeks of treatment.

During the maintenance phase, both 15 mg and 30 mg doses of upadacitinib continued to show superior efficacy in maintaining clinical remission and endoscopic response over 52 weeks, although higher doses were associated with increased risks of herpes zoster infections and other adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Induction and Maintenance Therapy for Crohn's Disease. Loftus, EV., Panés, J., Lacerda, AP., 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]

In a cohort of patients with medically refractory Crohn's disease, treatment with upadacitinib led to subjective responses in 25% and objective responses in 42% of patients, indicating its potential effectiveness in real-world settings.

Even at lower doses than those currently being studied, upadacitinib demonstrated a favorable benefit-to-risk profile, suggesting it may be a safe option for patients with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center. Traboulsi, C., Ayoub, F., Silfen, A., et al.[2023]

In a long-term study of 107 patients with Crohn's disease, upadacitinib demonstrated sustained clinical remission rates of around 54-61% over 30 months, indicating its efficacy as a treatment.

While upadacitinib showed long-term benefits, the safety profile revealed that higher doses (30 mg) were associated with increased rates of adverse events compared to lower doses (15 mg), consistent with its known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study. D'Haens, G., Panés, J., Louis, E., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03345849

NCT03345849 | A Study of the Efficacy and Safety ... Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn's Disease Regardless of Prior Biologic Exposure. Clin Gastroenterol Hepatol. 2024 Oct;22(10): ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2212728

Upadacitinib Induction and Maintenance Therapy for ... Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32044319/

Efficacy and Safety of Upadacitinib in a Randomized Trial ... Results: Among the 220 patients in the study, clinical remission was achieved by 13% of patients receiving 3 mg upadacitinib, 27% of patients receiving 6 mg ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1542356525001545

Real-World Effectiveness and Safety of Upadacitinib in ... Among 334 CD patients, 52.1% achieved clinical remission at 12 weeks and 42.7% endoscopic remission at 6 months. Higher BMI, disease duration and advanced ...

5. news.abbvie.com news.abbvie.com/2022-02-24-Second-Phase-3-Induction-Study-Confirms-Upadacitinib-RINVOQ-R-Improved-Clinical-and-Endoscopic-Outcomes-in-Patients-with-Crohns-Disease

Second Phase 3 Induction Study Confirms Upadacitinib ... Second Phase 3 Induction Study Confirms Upadacitinib (RINVOQ®) Improved Clinical and Endoscopic Outcomes in Patients with Crohn's Disease.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03345836

NCT03345836 | A Study of the Efficacy and Safety ... CDAI scores below 150 represent remission and scores over 450 represent very severe Crohn's disease. Results were based on non-responder imputation ...

7. cghjournal.org cghjournal.org/article/S1542-3565(25)00154-5/fulltext

Real-World Effectiveness and Safety of Upadacitinib in ... Among 334 CD patients, 52.1% achieved clinical remission at 12 weeks and 42.7% endoscopic remission at 6 months. Higher BMI, disease duration ...

8. pharmacytimes.com pharmacytimes.com/view/fda-approves-updated-indication-for-upadacitinib-in-patients-with-ibd

FDA Approves Updated Indication for Upadacitinib in ... During the maintenance trial, 42% and 52% of patients who received 15 mg and 30 mg of upadacitinib, respectively, achieved clinical remission at ...