Upadacitinib for Crohn's Disease

No longer recruiting at 123 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Disqualifiers: Pregnancy, Non-compliance, Others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the long-term effectiveness and safety of Upadacitinib for individuals with Crohn's disease, a condition that inflames the digestive tract, leading to symptoms like abdominal pain and diarrhea. Participants will receive one of two daily doses of Upadacitinib to evaluate its efficacy and tolerability. Eligibility is limited to those who have completed a previous related study and are not planning to become pregnant. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must comply with medication requirements from the previous study, M13-740.

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

Research has shown that upadacitinib is generally well-tolerated by people with Crohn's disease. In one study involving about 334 patients, many reached a symptom-free state within 12 weeks of treatment. Another study over two years found that upadacitinib remained safe, with no new serious safety issues.

In everyday use, upadacitinib demonstrated good short-term safety, with patients responding well to the treatment. It is important to note that this drug has been tested in various studies and is monitored for any side effects. While some individuals might experience side effects, these studies suggest that upadacitinib is relatively safe for long-term use in treating Crohn's disease. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about upadacitinib for Crohn's disease because it offers a novel approach by targeting the Janus kinase (JAK) pathway, which plays a crucial role in the inflammatory process. Unlike traditional treatments such as corticosteroids or biologics like infliximab that focus on suppressing the immune response, upadacitinib specifically inhibits JAK enzymes, potentially reducing inflammation more precisely and with fewer side effects. This targeted mechanism could lead to more effective management of Crohn's disease symptoms and improved quality of life for patients. Additionally, the convenience of a once-daily oral dose makes it an attractive alternative for those seeking treatments beyond injections or infusions.

What evidence suggests that Upadacitinib might be an effective treatment for Crohn's Disease?

Research shows that upadacitinib may effectively treat Crohn's disease. One study found that 52.1% of patients were symptom-free within 12 weeks, and 42.7% showed no signs of the disease in tests after 6 months. Another study found that 62% to 67% of patients were symptom-free at various times. Upadacitinib also outperformed a placebo for patients with moderate-to-severe Crohn's disease. These results suggest that upadacitinib could help manage Crohn's disease symptoms over time. Participants in this trial will receive either Dose A or Dose B of upadacitinib to further evaluate its effectiveness. ^{2 3 4 5 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for individuals with Crohn's Disease who have completed the M13-740 study up to Week 52. Women must be postmenopausal, surgically sterile, or using birth control. Those unsuitable as per the investigator, pregnant women, or those planning pregnancy during the study are excluded.

Inclusion Criteria

I am a woman who is either postmenopausal, surgically sterile, or using birth control.

Participant must have completed Study M13-740 through Week 52.

I am a woman who is postmenopausal, surgically sterile, or using birth control.

Exclusion Criteria

Participant is not in compliance with prior and concomitant medication requirements and procedures throughout Study M13-740.

I am not pregnant nor planning to become pregnant during the study.

For any reason participant is considered by the investigator to be an unsuitable candidate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants receive repeated administration of Upadacitinib (ABT-494) to evaluate long-term efficacy, safety, and tolerability

Up to 96 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib (ABT-494)

Trial Overview The trial is testing Upadacitinib (ABT-494) for long-term effectiveness and safety in treating Crohn's Disease. It involves repeated doses of this medication over an extended period to monitor its sustained impact on patients.

How Is the Trial Designed?

Group I: Upadacitinib (ABT-494) Dose B Experimental Treatment 1 Intervention

Open label dose B QD

Group II: Upadacitinib (ABT-494) Dose A Experimental Treatment 1 Intervention

Open label dose A once daily (QD)

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 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 phase 2 trial involving 220 adults with moderate to severe Crohn's disease, upadacitinib demonstrated significant efficacy in inducing endoscopic remission, particularly at the 24 mg dose, compared to placebo.

While upadacitinib showed promising results, it was associated with higher rates of infections and increased cholesterol levels, indicating a need to carefully consider its safety profile in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Upadacitinib in a Randomized Trial of Patients With Crohn's Disease. Sandborn, WJ., Feagan, BG., Loftus, EV., et al.[2021]

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]

Tofacitinib has been evaluated for safety and efficacy in Crohn's disease through two phase II trials, showing no new safety concerns but also no significant improvement over placebo in the primary clinical response measure.

Despite the lack of significant results in larger trials, smaller studies and post hoc analyses suggest that tofacitinib may still provide clinical and biological benefits for some patients with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Tofacitinib in Crohn's Disease and IBD-U: A Multicenter Study From the TROPIC Consortium. Fenster, M., Alayo, QA., Khatiwada, A., et al.[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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12506220/

Effectiveness and safety of upadacitinib in a real-world ... This is a large real-world study reporting outcomes in patients with CD treated with upadacitinib. Our data demonstrated good short-term ...

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

Effectiveness & Safety of Upadacitinib in Crohn’s Disease 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 ...

3. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1685/7967933

P0890 Real-World Outcomes of Upadacitinib in Crohn's Disease Clinical remission was achieved in 62%, 65% and 67% of patients at W12, 24, 52. FC and CRP levels returned to normal (<250 μg/g and <3 mg/ ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03345849

Study: Upadacitinib for Crohn's Disease (ClinicalTrials.gov) The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in adults with moderately and ...

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

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

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40704669/

Efficacy and safety of upadacitinib maintenance therapy in ... Efficacy and safety of upadacitinib maintenance therapy in patients with moderately to severely active Crohn's disease: 2-year results from ...