Upadacitinib Maintenance Therapy for Crohn's Disease

(U-ENDURE Trial)

Not currently recruiting at 932 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Disqualifiers: Infections, Hypersensitivity, Dysplasia, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of upadacitinib as a long-term treatment for Crohn's Disease, a condition that causes inflammation in the digestive tract. The study compares different doses of upadacitinib and a placebo (a pill with no active ingredient) to determine which is most effective and safe. It seeks participants who have already shown improvement on upadacitinib in earlier studies, indicating positive changes in their Crohn's symptoms. Participants must have completed certain procedures in past related studies to join. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that upadacitinib, the treatment under study, has been tested in people with moderate-to-severe Crohn's disease. Results indicate that while it can be effective, some safety concerns exist.

One study found that people taking upadacitinib had a higher risk of infections, some serious enough to require hospitalization. Close monitoring is essential while using this treatment. Upadacitinib is already FDA-approved for other conditions, providing some understanding of its safety, but specific risks for Crohn's disease should be considered.

Prospective trial participants should weigh potential benefits against these risks. Consulting with a healthcare provider is crucial to understand personal implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about upadacitinib for Crohn's disease because it represents a novel approach compared to existing treatments. Unlike the standard treatments that primarily focus on suppressing the immune system broadly, upadacitinib specifically targets and inhibits Janus kinase (JAK) enzymes. This precision may allow for more effective control of inflammation with potentially fewer side effects. Moreover, the potential for different dosing options (Dose A and Dose B) offers flexibility in tailoring treatment to individual patient needs. This innovative mechanism and adaptability make upadacitinib a promising option for those with Crohn's disease.

What evidence suggests that this trial's treatments could be effective for Crohn's Disease?

Research has shown that upadacitinib, which participants in this trial may receive, effectively treats Crohn's disease. One study demonstrated that it outperformed a placebo in helping patients with moderate-to-severe Crohn's disease achieve significant symptom improvement, known as clinical remission. Specifically, 52.1% of patients reached clinical remission in just 12 weeks, indicating the treatment's rapid effectiveness. Additionally, 42.7% of patients showed reduced visible inflammation in their intestines, known as endoscopic remission, after 6 months. These results are promising for patients using upadacitinib. ^{3 5 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 adults with Crohn's Disease who showed improvement in previous studies (M14-431 or M14-433) and completed certain study procedures. Participants can still join if their final endoscopy was missed due to COVID-19.

Inclusion Criteria

Participant completes study procedures in the parent study. The final endoscopy for Studies M14-431 or M14-433 may be missing, if the endoscopy cannot be performed during the COVID-19 pandemic.

For Substudy 2: Participant completes Substudy 1. The Week 52 endoscopy may be missing, if the endoscopy cannot be performed during the COVID-19 pandemic.

Participant who achieved clinical response at the time described in the protocol and completes study procedures in the parent study/ substudy.

Exclusion Criteria

My recent colonoscopy shows significant inflammation.

I haven't started new medication or increased my current Crohn's disease medication dose in the last 3 months.

Participant at the final visit of M14-431 or M14-433 with any active or chronic recurring infections based on the investigator's assessment that makes the participant an unsuitable candidate for the study. Participants with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed and the infection is resolved, based on the investigator's assessment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Maintenance Treatment

Participants receive upadacitinib or placebo for maintenance treatment

52 weeks

Regular visits as per study protocol

Long-term Extension

Participants who complete the maintenance phase receive long-term treatment with upadacitinib or placebo

240 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib

Trial Overview The trial tests the long-term effectiveness and safety of Upadacitinib, a pill that targets specific proteins involved in inflammation, compared to a placebo in maintaining Crohn's Disease treatment effects.

How Is the Trial Designed?

Group I: Substudy 2: Cohort 5 Upadacitinib Dose B Experimental Treatment 1 Intervention

This is a long-term extension group which includes participants who complete Substudy 1 and will receive upadacitinib dose B for 240 weeks.

Group II: Substudy 2: Cohort 5 Upadacitinib Dose A Experimental Treatment 1 Intervention

This is a long-term extension group which includes participants who complete Substudy 1 and will receive upadacitinib dose A for 240 weeks.

Group III: Substudy 2: Cohort 5 Placebo Experimental Treatment 1 Intervention

This is a long-term extension group which includes participants who complete Substudy 1 and will receive placebo for 240 weeks.

Group IV: Substudy 2: Cohort 4 Upadacitinib Dose B Experimental Treatment 1 Intervention

This is a long-term extension group which includes participants who achieved clinical response in the open-label extended treatment period of study M14-431 and will receive upadacitinib dose B for 240 weeks.

Group V: Substudy 1: Cohort 3 Upadacitinib Dose B Experimental Treatment 1 Intervention

This is a maintenance group which includes participants who achieved clinical response to upadacitinib from the extended treatment period of studies M14-431 and M14-433 and will receive upadacitinib Dose B for 52 Weeks.

Group VI: Substudy 1: Cohort 2 Placebo Experimental Treatment 1 Intervention

This is a maintenance group which includes participants who received double-blind placebo in studies M14-431 and M14-433 and achieved clinical response will continue to receive blinded placebo for 52 Weeks.

Group VII: Substudy 1: Cohort 1 Upadacitinib Dose B Experimental Treatment 1 Intervention

This is a maintenance group which includes participants who achieved clinical response to upadacitinib in studies M14-431 and M14-433 and will receive upadacitinib dose B for 52 weeks.

Group VIII: Substudy 1: Cohort 1 Upadacitinib Dose A Experimental Treatment 1 Intervention

This is a maintenance group which includes participants who achieved clinical response to upadacitinib in studies M14-431 and M14-433 and will receive upadacitinib dose A for 52 weeks.

Group IX: Substudy 1: Cohort 1 Placebo Experimental Treatment 1 Intervention

This is a maintenance group which includes participants who achieved clinical response to upadacitinib in studies M14-431 and M14-433 and will receive placebo for 52 weeks.

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 phase II clinical trial involving 109 patients with BRAFV600E-mutant metastatic colorectal cancer, the combination of FOLFOXIRI with cetuximab did not show a higher objective response rate compared to FOLFOXIRI with bevacizumab, with response rates of 51% and 67% respectively.

The study found that patients receiving FOLFOXIRI plus cetuximab had significantly shorter progression-free survival (6.7 months) compared to those receiving FOLFOXIRI plus bevacizumab (10.7 months), indicating that bevacizumab-based chemotherapy is the preferred first-line treatment for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI Plus Cetuximab or Bevacizumab as First-Line Treatment of BRAFV600E-Mutant Metastatic Colorectal Cancer: The Randomized Phase II FIRE-4.5 (AIO KRK0116) Study. Stintzing, S., Heinrich, K., Tougeron, D., et al.[2023]

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 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]

In a study of 72 patients with microsatellite stable metastatic colorectal cancer, regorafenib or fruquintinib combined with sintilimab showed a median progression-free survival of 4.2 months and an overall survival of 10.5 months, indicating these combinations are viable third-line treatment options.

The treatment was generally well-tolerated, with only 15.3% of patients experiencing severe adverse events, and patients without liver metastasis showed better response rates and overall survival, suggesting they may benefit more from this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study. Nie, C., Lv, H., Chen, B., et al.[2022]

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]

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. 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 ...

5. 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 ...

6. rinvoqhcp.com rinvoqhcp.com/safety

RINVOQ® (upadacitinib) Safety Profile Patients treated with RINVOQ are at increased risk for developing infections that may lead to hospitalization or death.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03345836

NCT03345836 | A Study of the Efficacy and Safety ... The objective of this study is to evaluate the efficacy and safety of upadacitinib compared to placebo as induction therapy in participants with moderately and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7027977/

Exposure–Response Analyses for Upadacitinib Efficacy and ... Upadacitinib plasma concentrations, efficacy, and safety data from 216 subjects with moderate‐to‐severe active Crohn's disease (CD) from the 16‐ ...