Risankizumab for Ulcerative Colitis

(COMMAND Trial)

Not currently recruiting at 828 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Risankizumab

Disqualifiers: Hypersensitivity, Non-compliance, others

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 safety and effectiveness of risankizumab (Skyrizi) for individuals with ulcerative colitis (UC) who previously responded well to the drug. The trial consists of several parts: a year-long study where some participants receive a placebo (a treatment with no active drug) and two other studies where all participants receive risankizumab. Participants who complete these studies can join an extension to continue treatment until the drug becomes available on the market. Those who completed a previous study with a positive response to risankizumab may be well-suited for this trial. As a Phase 3 trial, this study is the final step before FDA approval, allowing participants to contribute to the potential availability of a new UC treatment.

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, it mentions that participants must comply with prior and current medication requirements from previous studies, so it's best to discuss your specific situation with the study team.

Is there any evidence suggesting that risankizumab is likely to be safe for humans?

Research has shown that risankizumab is generally safe for people with ulcerative colitis. Common side effects include joint pain, fever, and injection site reactions, occurring in more than 3% of patients. Some people have also reported colds and headaches. In studies, risankizumab was tested on individuals with moderate-to-severe cases and proved safe over long periods. The treatment is already approved for other conditions, indicating its safety for humans. Always consult a doctor about possible risks before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for ulcerative colitis?

Risankizumab is unique because it targets interleukin-23 (IL-23), a specific protein involved in inflammation, which is different from many current ulcerative colitis treatments that target a broader range of inflammatory processes. This specificity can potentially lead to fewer side effects and a more effective reduction of symptoms. Additionally, risankizumab is administered by subcutaneous injection, which is a convenient option compared to some treatments that require intravenous administration. Researchers are excited about risankizumab because it offers a new approach that could improve patient outcomes and quality of life by reducing inflammation more precisely.

What evidence suggests that risankizumab might be an effective treatment for ulcerative colitis?

Research has shown that risankizumab effectively treats ulcerative colitis (UC). Studies have found that it can reduce symptoms like frequent bowel movements and bloody stools within 12 weeks. After one year, many patients continue to experience symptom relief. In this trial, participants will receive different doses of risankizumab. Previous studies observed that risankizumab greatly increased the number of people experiencing less abdominal pain and urgency to use the bathroom. Overall, risankizumab may effectively manage the challenging symptoms of UC. ^{3 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for people with ulcerative colitis who responded to risankizumab in a previous study. They must not have allergies to risankizumab, its ingredients, or substances from Chinese hamster ovary cells. Participants should be compliant with medication requirements from the prior study.

Inclusion Criteria

Participants who have completed Study M16-067 and have achieved clinical response as defined in the protocol.

Exclusion Criteria

Participant is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.

Participant is not in compliance with prior and concomitant medication requirements throughout Studies M16-067.

I am not allergic to risankizumab, its ingredients, or products from Chinese hamster ovary cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Substudy 1: Maintenance

52-week, randomized, double-blind, placebo-controlled maintenance study

52 weeks

Substudy 2: Exploratory Maintenance

52-week, randomized, exploratory maintenance study

52 weeks

Substudy 3: Open-label Extension

Open-label long-term extension study for participants who completed Substudy 1 or 2

Long-term

Continuous Treatment Extension (CTE)

Open-label extension for Substudy 3 completers to ensure continuous treatment with risankizumab

Until risankizumab becomes commercially available

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Risankizumab

Trial Overview The trial tests the safety and effectiveness of risankizumab over 52 weeks compared to a placebo. It includes three sub-studies: one double-blind controlled study, one exploratory study, and an open-label extension for certain participants affected by COVID-19 or geopolitical issues.

How Is the Trial Designed?

Group I: Substudy 3: OL Extension Risankizumab Experimental Treatment 1 Intervention

Participants who completed Sub-study 1 or 2 receive open-label risankizumab in Sub-study 3.

Group II: Substudy 2: Open-label (OL) Clinical Assessment Risankizumab Experimental Treatment 1 Intervention

Participants randomized to receive risankizumab dose 1 administered by subcutaneous (SC) injection.

Group III: Substudy 2: OL Therapeutic Drug Monitoring Risankizumab Experimental Treatment 1 Intervention

Participants randomized to receive risankizumab dose 1 administered by subcutaneous (SC) injection.

Group IV: Substudy 1: Double-blind Risankizumab Dose 2 Experimental Treatment 1 Intervention

Participants randomized to receive risankizumab dose 2 administered by subcutaneous (SC) injection.

Group V: Substudy 1: Double-blind Risankizumab Dose 1 Experimental Treatment 1 Intervention

Participants randomized to receive risankizumab dose 1 administered by subcutaneous (SC) injection.

Group VI: OL Continuous Treatment Extension - Dose 2 Experimental Treatment 1 Intervention

Participants who complete Sub-study 3 and continue to tolerate and derive benefit from receiving risankizumab, will continue to receive risankizumab based on their assignment during Sub-study 3. Participants completing Sub-study 3 and received risankizumab rescue therapy in any sub-study will receive risankizumab Dose 2 administered by subcutaneous (SC) injection.

Group VII: OL Continuous Treatment Extension - Dose 1 Experimental Treatment 1 Intervention

Participants who complete Sub-study 3 and continue to tolerate and derive benefit from receiving risankizumab, will continue to receive risankizumab based on their assignment during Sub-study 3. Participants completing Sub-study 3 without receiving risankizumab rescue therapy in any sub-study will receive risankizumab Dose 1 administered by subcutaneous (SC) injection.

Group VIII: Substudy 1: Double-blind Placebo Placebo Group 1 Intervention

Participants randomized to receive placebo for risankizumab administered by subcutaneous (SC) injection.

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 100 patients with moderate-to-severe Crohn's disease who had previously failed multiple treatments, risankizumab achieved a steroid-free clinical remission rate of 45.8% and a clinical response rate of 78.5% by week 12, indicating its effectiveness in a real-world setting.

The treatment was generally well-tolerated, with 20 adverse events reported, including 7 serious cases, but the majority of patients experienced significant improvements in their condition, highlighting risankizumab's potential as a viable option for refractory Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study. Fumery, M., Defrance, A., Roblin, X., et al.[2023]

Vedolizumab has been shown to be effective in managing ulcerative colitis, providing significant improvements in patient symptoms and disease control.

The review also highlights that vedolizumab has a favorable safety profile, making it a suitable treatment option for patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of vedolizumab for the treatment of ulcerative colitis. Lau, MS., Tsai, HH.[2020]

Upadacitinib and risankizumab effectively modify immune response mechanisms in patients with inflammatory bowel disease (IBD) who do not respond to anti-TNF-α therapies, as shown by significant decreases in upregulated immune modules and cell types associated with inflammation.

In a study involving tissue transcriptomic data from IBD patients, upadacitinib treatment led to a notable reduction in the expression of inflammatory markers and immune cell types in responders, indicating its potential to improve clinical outcomes in TNF-IR patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Response of Upadacitinib and Risankizumab Is Associated With Reduced Inflammatory Bowel Disease Anti-TNF-α Inadequate Response Mechanisms. Wang, J., Macoritto, M., Guay, H., et al.[2023]

Mirikizumab, an anti-interleukin-23 treatment, significantly improved histological and endoscopic outcomes in patients with moderately-to-severely active ulcerative colitis, showing better results compared to placebo in a study involving 1162 patients at Week 12 and 544 patients at Week 40.

Achieving early endoscopic and histological improvements with mirikizumab was linked to better long-term outcomes, including clinical remission and reduced symptoms, highlighting the importance of early intervention in managing ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. Magro, F., Pai, RK., Kobayashi, T., et al.[2023]

In a study involving 108 patients with moderately to severely active Crohn's disease, extended intravenous treatment with risankizumab significantly improved clinical remission rates, with 53% of patients achieving remission by week 26 after 12 weeks of treatment.

Risankizumab was well tolerated, with most adverse events being mild or moderate, and it successfully maintained remission in 71% of patients at week 52, indicating its potential as a safe and effective long-term treatment option for Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. Feagan, BG., Panés, J., Ferrante, M., et al.[2022]

In a long-term study of 65 patients with moderate-to-severe Crohn's disease, risankizumab was well tolerated over a median of 33 months, with no new safety concerns and a low rate of serious adverse events (24.6 events/100 patient-years).

Efficacy was maintained throughout the study, with over 71% of patients achieving clinical remission and more than 42% achieving endoscopic remission, indicating that risankizumab remains effective for long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study. Ferrante, M., Feagan, BG., Panés, J., et al.[2022]

Vedolizumab demonstrated significant efficacy in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD), with 63.9% of UC patients and 61.7% of CD patients achieving clinical remission by week 52.

Bio-naïve patients with UC experienced a lower risk of serious adverse events compared to those previously treated, indicating a favorable safety profile for vedolizumab in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis. Attauabi, M., Madsen, GR., Bendtsen, F., et al.[2023]

Risankizumab, an IL-23 p19 inhibitor, demonstrated significant efficacy in inducing clinical remission and endoscopic response in patients with moderately to severely active Crohn's disease, with remission rates of up to 45% compared to 25% in the placebo group in the ADVANCE trial.

The treatment was well tolerated, with a similar incidence of adverse events across all groups, and the one death in the risankizumab group was determined to be unrelated to the drug, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. D'Haens, G., Panaccione, R., Baert, F., et al.[2022]

In a study involving 106 patients with active Crohn's disease, risankizumab significantly reduced the expression of genes related to the IL-23/IL-17 axis and immune response pathways by Week 12, indicating its mechanism of action in treating the disease.

The transcriptomic changes in the colon after risankizumab treatment were linked to clinical and endoscopic remission, showing that the drug effectively modulates key biological pathways associated with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective IL-23 Inhibition by Risankizumab Modulates the Molecular Profile in the Colon and Ileum of Patients With Active Crohn's Disease: Results From a Randomised Phase II Biopsy Sub-study. Visvanathan, S., Baum, P., Salas, A., et al.[2022]

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. skyrizihcp.com skyrizihcp.com/gastroenterology/ulcerative-colitis/efficacy

Efficacy - SKYRIZI® (risankizumab-rzaa) for UC SKYRIZI® efficacy data for ulcerative colitis, including durable remission & early disease control. See Important Safety Information and Prescribing ...

2. skyrizi.com skyrizi.com/ulcerative-colitis/skyrizi-results

SKYRIZI® Results (risankizumab-rzaa) SKYRIZI is proven to deliver remission at 12 weeks and 1 year, which means few to no symptoms (like frequent bowel movements and bloody stools) and visible ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11772864/

Risankizumab efficacy and safety based on prior ... Results from this post hoc analysis demonstrate that risankizumab is effective and well tolerated for the treatment of UC in the non-AT-IR and ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2821291

Risankizumab for Ulcerative Colitis: Two Randomized ... Findings Among the 975 patients analyzed in the induction trial, 1200 mg of risankizumab significantly increased the rates of clinical remission ...

5. news.abbvie.com news.abbvie.com/2023-03-23-Risankizumab-SKYRIZI-R-Achieves-Primary-and-All-Secondary-Endpoints-in-Phase-3-Induction-Study-in-Patients-With-Ulcerative-Colitis

Risankizumab (SKYRIZI®) Achieves Primary and All ... Risankizumab may help patients coping with the challenging symptoms of ulcerative colitis, which include abdominal pain, bowel urgency and fecal incontinence.

6. skyrizihcp.com skyrizihcp.com/gastroenterology/ulcerative-colitis/safety

Safety Profile - SKYRIZI® (risankizumab-rzaa) for UC Most common (≥3%) adverse reactions associated with SKYRIZI in ulcerative colitis are arthralgia in induction, and arthralgia, pyrexia, injection site reactions ...

7. skyrizi.com skyrizi.com/important-safety-information

Important Safety Information | SKYRIZI® (risankizumab-rzaa) The most common side effects of SKYRIZI in people treated for Crohn's disease and ulcerative colitis include: upper respiratory infections, headache, joint pain ...

8. skyrizihcp.com skyrizihcp.com/gastroenterology/ulcerative-colitis

Ulcerative Colitis Treatment - SKYRIZI® (risankizumab-rzaa) Most common (≥3%) adverse reactions associated with SKYRIZI in ulcerative colitis are arthralgia in induction, and arthralgia, pyrexia, injection site reactions ...

9. 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 ...