Risankizumab vs Ustekinumab for Crohn's Disease

(SEQUENCE Trial)

Recruiting at 407 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

527 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug, risankizumab, against an existing drug, ustekinumab, to see which works better for adults with moderate to severe Crohn's Disease. The drugs help by reducing gut inflammation. Participants will receive the drugs through injections and be monitored over time. Risankizumab has been studied as a maintenance therapy for moderately to severely active Crohn's disease in previous trials.

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 Ustekinumab safe for treating Crohn's Disease?

Ustekinumab (Stelara) is generally well tolerated for treating Crohn's Disease, with serious infections and cancers being rare. It is considered a safe option for patients who have not responded to other treatments. ^{1 2 3 4 5}

How do the drugs Risankizumab and Ustekinumab differ from other treatments for Crohn's Disease?

Risankizumab and Ustekinumab are unique because they target specific proteins involved in inflammation, with Risankizumab focusing on IL-23 and Ustekinumab on both IL-12 and IL-23, offering alternatives for patients who haven't responded to other treatments like TNF antagonists. ^{1 2 5 6 7}

What data supports the effectiveness of the drugs Risankizumab and Ustekinumab for treating Crohn's Disease?

Ustekinumab has been shown to help about 50% of Crohn's Disease patients achieve clinical remission after one year, and it is generally well tolerated. Risankizumab and Ustekinumab are both approved for treating moderate to severe Crohn's Disease, with ongoing studies comparing their effectiveness. ^{1 2 5 8 9}

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

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 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]

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]

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]

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]

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]

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]

Citations

1. United States 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. [2018]

4. United States 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study. [2022]

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

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. [2023]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of ustekinumab for induction of remission in patients with Crohn's disease: A multicenter Israeli study. [2021]

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

Risankizumab-rzaa: A New Therapeutic Option for the Treatment of Crohn's Disease. [2023]