Risankizumab vs Ustekinumab for Crohn's Disease

(SEQUENCE Trial)

Not currently recruiting at 495 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: Biologics, Investigational agents

Disqualifiers: Ulcerative colitis, Indeterminate colitis, 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

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 two treatments, risankizumab and ustekinumab, for individuals with moderate to severe Crohn's disease, a condition causing inflammation in the digestive tract. Researchers continue to study risankizumab, while ustekinumab has already received approval for use. Participants will be divided into groups to receive either risankizumab or ustekinumab and will undergo regular check-ups to monitor changes in their condition. This trial suits individuals who have had Crohn's disease for at least three months and have not found success with other treatments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received certain biologic agents before the trial, so it's best to discuss your current medications with the trial team.

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

Research has shown that risankizumab is generally safe for people with Crohn's disease. In one study, patients who used risankizumab for a year experienced good results with manageable side effects. Another study in real-world settings found that many patients with difficult-to-treat Crohn's disease responded well to risankizumab, with no major safety issues identified.

Ustekinumab, already approved for treating moderate to severe Crohn's disease, has undergone thorough safety testing. Most people tolerate it well, and serious side effects are rare.

Overall, both treatments have demonstrated positive safety records in past studies, making them promising options for people with Crohn's disease. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about risankizumab for Crohn's disease because it targets a specific protein called IL-23, which plays a crucial role in the inflammation process. Unlike current treatments like infliximab and adalimumab that often target TNF-alpha, risankizumab offers a different approach by focusing on this distinct pathway. Additionally, the dosing schedule is flexible, starting with intravenous doses followed by subcutaneous injections, which might offer convenience and sustained relief for patients.

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

This trial will compare Risankizumab and Ustekinumab for treating Crohn's disease. Studies have shown that Risankizumab, which participants in this trial may receive, effectively treats Crohn's disease. In real-world settings, about 58% of patients improved without needing steroids, and around 59% experienced significant symptom relief after three months of treatment. Ustekinumab, another treatment option in this trial, is already approved for Crohn's and works well for moderate to severe cases. Both treatments have shown promising results in reducing Crohn's symptoms, with Risankizumab demonstrating strong early success. ^{1 3 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with moderate to severe Crohn's Disease for at least 3 months, having a CDAI score of 220-450. They must have had an inadequate response or intolerance to anti-TNF therapies and cannot have used p19 or p40 inhibitors like risankizumab or ustekinumab before.

Inclusion Criteria

I have been diagnosed with moderate to severe Crohn's Disease.

My Crohn's disease is moderately active.

I have not responded well to one or more anti-TNF treatments.

Exclusion Criteria

I have been treated with medications like risankizumab or ustekinumab.

I have not used any experimental drugs or certain approved biologic treatments before starting this study.

I have been diagnosed with ulcerative colitis or indeterminate colitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive intravenous doses of risankizumab or ustekinumab at Week 0, 4, 8 followed by subcutaneous doses every 8 weeks through Week 48

48 weeks

Regular visits at a hospital or clinic

Treatment Part 2

Participants who received risankizumab in Part 1 and completed the Week 48 visit will continue to receive subcutaneous risankizumab for up to an additional 220 weeks

220 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Risankizumab
• Ustekinumab

Trial Overview The trial is testing the effectiveness of Risankizumab compared to Ustekinumab in treating Crohn's Disease. Participants are randomly assigned to receive either drug via IV initially, then SC doses every eight weeks up to Week 48, with possible extension for Risankizumab recipients.

How Is the Trial Designed?

Group I: Risankizumab Dose A Followed by Dose B Experimental Treatment 1 Intervention

Participants will receive intravenous risankizumab dose A at Week 0, 4 ,8 followed by subcutaneous (SC) risankizumab dose B every 8 weeks through Week 48. Participants who complete the Week 48 visit will continue SC risankizumab for up to an additional 220 weeks.

Group II: Ustekinumab Active Control 1 Intervention

Participants will receive weight-based intravenous ustekinumab at Week 0 followed by subcutaneous ustekinumab every 8 weeks through Week 48.

Risankizumab is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Skyrizi for:

• Moderate-to-severe Crohn's disease

Approved in United States as Skyrizi for:

• Moderate-to-severe Crohn's disease
• Moderate-to-severe plaque psoriasis

Approved in European Union as Skyrizi for:

• Moderate-to-severe Crohn's disease
• Moderate-to-severe plaque psoriasis
• Psoriatic arthritis

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

Ustekinumab (STELARA) is a safe and effective treatment for skin conditions related to inflammatory bowel diseases (IBD), including metastatic Crohn's disease and pyoderma gangrenosum, based on a review of 22 articles.

It also effectively addresses paradoxical skin reactions caused by TNF-α inhibitors, such as psoriasis, particularly when these reactions do not improve with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases. Wu, J., Smogorzewski, J.[2021]

In a comparison of risankizumab (RZB) and ustekinumab (UST) for treating Crohn's disease, RZB showed significantly higher rates of clinical and endoscopic improvement during the induction phase, with 15% more patients achieving CDAI remission and 26% more showing endoscopic response.

After the maintenance phase, the rates of CDAI remission were similar between RZB and UST, but RZB still demonstrated better endoscopic response and remission rates, indicating that while both treatments are effective, RZB may offer advantages during initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease. Dubinsky, M., Ma, C., Griffith, J., et al.[2023]

Risankizumab-rzaa, a selective IL-23 inhibitor, has been shown to significantly improve clinical remission and endoscopic response in patients with moderate to severe Crohn's disease, based on results from three phase 3 studies involving multiple patients.

The safety profile of risankizumab-rzaa is comparable to other advanced therapies for Crohn's disease, with common side effects including nasopharyngitis and abdominal pain, making it a viable treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab-rzaa: A New Therapeutic Option for the Treatment of Crohn's Disease. Choi, D., Sheridan, H., Bhat, S.[2023]

In a study of 36 adults with Crohn's disease, 61% responded to ustekinumab treatment after one year, but no distinct gene expression signature was found to predict response, indicating that more research is needed to identify reliable biomarkers.

Among nonresponders, an increased inflammatory response was observed, with 68 genes linked to cytokine activity and chemokine receptor binding, suggesting that these pathways may play a role in treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. Granot, M., Braun, T., Efroni, G., et al.[2023]

In a study of 463 Crohn's disease patients treated with ustekinumab for at least 6 months, 56% achieved remission and 70% had a positive response by week 16, demonstrating its effectiveness in real-world settings.

Ustekinumab was found to be safe for long-term use, with an 18% discontinuation rate per patient-year and only 8.4% of patients reporting adverse events, indicating a favorable safety profile in a refractory patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study. Chaparro, M., Baston-Rey, I., Fernández-Salgado, E., et al.[2022]

In a systematic review of five randomized controlled trials involving patients with moderate-to-severe Crohn's disease who were nonresponsive or intolerant to TNF-antagonist therapy, ustekinumab and vedolizumab showed no significant differences in clinical response or remission during both induction and maintenance phases.

The safety profiles of ustekinumab and vedolizumab were also comparable, with no significant differences in the risk of adverse events, indicating that both treatments are similarly safe for patients with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An indirect comparison of ustekinumab and vedolizumab in the therapy of TNF-failure Crohn's disease patients. Kawalec, P., Moćko, P.[2019]

Ustekinumab is an effective treatment for adults with moderately to severely active Crohn's disease who have not responded to or are intolerant of other therapies, showing improved clinical response and remission rates in pivotal phase III trials.

The drug has a unique mechanism of action targeting IL-12 and IL-23 cytokines, and it is generally well tolerated, with serious side effects like infections and malignancies being rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. Lamb, YN., Duggan, ST.[2018]

A study involving 117 Crohn's disease patients, including 39 elderly (≥65 years) and 78 nonelderly (<65 years), found that ustekinumab (UST) is safe and effective for treating elderly patients, with nearly 90% experiencing a clinical response.

Elderly patients were less likely to achieve complete clinical remission compared to nonelderly patients (28.2% vs. 52.6%), but there were no significant differences in adverse events or complications between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. Garg, R., Aggarwal, M., Butler, R., et al.[2023]

Citations

1. skyrizihcp.com skyrizihcp.com/gastroenterology/crohns-disease/efficacy

Efficacy Data - SKYRIZI® (risankizumab-rzaa) for Crohn's Results at 52 weeks are among 382 patients who achieved clinical response‡ after 12 weeks of treatment with SKYRIZI in induction trials. aContinuous placebo ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40857638/

Long-term Outcomes of Patients with Crohn's Disease ... Background: Cumulative data suggest that risankizumab is an effective and safe treatment for patients with Crohn's disease (CD).

3. mayoclinic.org mayoclinic.org/medical-professionals/digestive-diseases/news/examining-the-real-world-effectiveness-and-safety-of-risankizumab-in-patients-with-crohns-disease/mac-20589059

Examining the real-world effectiveness and safety of ... Researchers shared real-world effectiveness data and demonstrated how RZB performs in patients with prior therapy exposure and other ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38215029/

Real-world Effectiveness and Safety of Risankizumab in ... In this real-world study of multirefractory Crohn's disease patients, risankizumab was effective, with 58.2% and 27.3% achieving steroid-free clinical response ...

5. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1586/7967969

P0832 Real-world effectiveness of risankizumab in Crohn's ... Rates of clinical remission were 59% (211/358), 50% (77/154), and 44% (14/32) at 3, 6 and 12 months. Rates of clinical remission for ustekinumab ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8684487/

Long-Term Safety and Efficacy of Risankizumab Treatment in ... Results from the phase 2 M15-993 study showed that risankizumab was effective and well tolerated through 52 weeks in patients with moderate-to-severe CD, the ...

7. skyrizi.com skyrizi.com/crohns/skyrizi-results

Results With SKYRIZI® (risankizumab-rzaa) for Crohn's ... Many people achieved little to no visible evidence of active Crohn's EVEN AT 1 YEAR. Based on areas that were assessed on endoscopy. In the clinical trial, ...