Risankizumab for Ulcerative Colitis

(COMMAND Trial)

Recruiting at 692 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

1242 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Risankizumab for treating ulcerative colitis?

Research shows that Risankizumab, which targets a specific protein involved in inflammation, is effective in treating Crohn's disease, a condition similar to ulcerative colitis. This suggests it may also help reduce inflammation in ulcerative colitis. ^{1 2 3 4 5}

Is risankizumab safe for humans?

Risankizumab has been studied for safety in patients with Crohn's disease, and these studies have shown it to be generally safe for human use. ^{6 7 8 9 10}

How is the drug Risankizumab different from other treatments for ulcerative colitis?

Risankizumab is unique because it targets interleukin-23 (IL-23), a protein involved in inflammation, making it potentially effective for patients who do not respond well to other treatments like anti-TNF therapies. This approach is different from many existing treatments for ulcerative colitis, which often target other pathways. ^{1 2 3 11 12}

What is the purpose of this trial?

The purpose of this study is to evaluate safety and efficacy of risankizumab in participants with ulcerative colitis (UC) in participants who responded to induction treatment with risankizumab in a prior AbbVie study of risankizumab in UC. This study consists of three sub-studies and a Continuous Treatment Extension (CTE): Substudy 1 is a 52-week, randomized, double-blind, placebo-controlled maintenance study; Substudy 2 is 52-week, randomized, exploratory maintenance study; and Substudy 3 is an open-label long-term extension study for participants who completed Substudy 1 or 2, or participants who responded to induction treatment in Study M16-067 with no final endoscopy due to the Covid-19 pandemic or due to the geopolitical conflict in Ukraine and surrounding impacted regions. The CTE is an open-label extension for Substudy 3 completers to ensure continuous treatment with risankizumab until such time that risankizumab becomes commercially available and/or the subject can access treatment locally.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. [2022]

4. England 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. [2022]

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

Resolving Histological Inflammation in Ulcerative Colitis With Mirikizumab in the LUCENT Induction and Maintenance Trial Programmes. [2023]

6. Netherlands 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. [2023]

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

One-year effectiveness and safety of ustekinumab in ulcerative colitis: a multicenter real-world study from Italy. [2022]

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

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis From 2 Tertiary IBD Centers in the United States. [2023]

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

Review of vedolizumab for the treatment of ulcerative colitis. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. [2022]

12. England 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. [2022]