Upadacitinib for Crohn's Disease

(U-EMPOWER Trial)

Recruiting at 79 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

Trial Summary

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.

How is the drug Upadacitinib different from other treatments for Crohn's disease?

Upadacitinib is unique because it is an oral medication that selectively inhibits Janus kinase 1 (JAK-1), a protein involved in inflammation, and it has shown promise in treating Crohn's disease, especially in patients who have not responded to other treatments. It is already approved for ulcerative colitis and rheumatoid arthritis, making it a novel option for Crohn's disease. ^{1 2 3 4 5}

What is the purpose of this trial?

Crohn's disease (CD) is a long-lasting disease that causes severe inflammation (redness, swelling), in the digestive tract, most often affecting the bowels. It can cause many different symptoms including abdominal pain, diarrhea, tiredness, and weight loss. This study will assess how safe and effective oral Upadacitinib is in treating moderately to severely active Crohn's Disease in pediatric participants aged 2 to 18 years old who have had inadequate response, loss of response, intolerance, or medical contraindications to corticosteroids, immunosuppressants, and/or biologic therapy. Upadacitinib (RINVOQ) is a drug approved in adults for moderate- to severely active CD and is being developed for moderate- to severely active CD in pediatric participants. This study is conducted in 2 periods: Period 1 is comprised of two phases: a 12-week open-label induction phase which means that the study doctor and participants know that participants will receive UPA Dose-A (or the adult equivalent based on body weight) followed by a 52-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 156-week open-label extension of Period 1. Approximately 110 pediatric participants with moderate to severely active CD will be enrolled at approximately 92 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 have a safety follow up for 30 days after discontinuation from any time point within the study. There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular (weekly, monthly) 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.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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 have been diagnosed with a primary immune deficiency.

Timeline

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Upadacitinib Induction and Maintenance Therapy for Crohn's Disease. [2023]

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

Upadacitinib Is Safe and Effective for Crohn's Disease: Real-World Data from a Tertiary Center. [2023]

5. United States 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. [2022]