Upadacitinib Maintenance Therapy for Crohn's Disease

(U-ENDURE Trial)

Recruiting at 782 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

747 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A multicenter study to evaluate the efficacy and safety of maintenance and long-term treatment administration of upadacitinib, an orally administered Janus kinase 1 inhibitor, in adult participants with Crohn's Disease.

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.

What makes the drug Upadacitinib unique for treating Crohn's Disease?

Upadacitinib is unique because it is a Janus kinase (JAK) inhibitor, which works by blocking specific enzymes involved in the inflammatory process, offering a different mechanism of action compared to traditional treatments for Crohn's Disease that often focus on suppressing the immune system more broadly. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Upadacitinib for Crohn's Disease?

Research shows that Upadacitinib, a drug used for other conditions like rheumatoid arthritis and ulcerative colitis, has been effective in increasing clinical remission in Crohn's Disease patients over 12 and 52 weeks. Additionally, it has shown positive results in long-term studies and real-world settings, with a good balance between benefits and risks. ^{6 7 8 9 10}

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 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 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 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 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 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]

Citations

1. 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]

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

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

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

In moderate-to-severe Crohn disease, upadacitinib increased clinical remission at 12 and 52 wk. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Current Therapeutic Strategies in BRAF-Mutant Metastatic Colorectal Cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Regorafenib enhances anti-PD1 immunotherapy efficacy in murine colorectal cancers and their combination prevents tumor regrowth. [2022]

8. United States 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. [2023]

9. Switzerland 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Effective management of advanced colon cancer genotyping microsatellite stable/microsatellite instable-low with Kirsten rat sarcoma viral oncogene mutation using nivolumab plus ipilimumab combined with regorafenib and irinotecan: A case report. [2022]