Risankizumab for Pediatric Crohn's Disease

(RISE Trial)

Recruiting at 87 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Disqualifiers: Ulcerative colitis, Immunodeficiency, Abscess, 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

110 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Risankizumab for treating Crohn's disease?

Research shows that Risankizumab is effective in treating moderate to severe Crohn's disease, with studies demonstrating its ability to help patients achieve remission and maintain it over time. ^{1 2 3 4 5}

Is risankizumab safe for humans?

Risankizumab has been shown to have acceptable safety in patients with moderate-to-severe Crohn's disease in several studies, including long-term safety evaluations. ^{1 2 4 6 7}

How is the drug Risankizumab unique for treating Crohn's disease?

Risankizumab is unique because it targets a specific part of the immune system called interleukin-23 (IL-23), which is involved in inflammation, making it different from other treatments that may target broader immune responses. It is used both as an initial (induction) and ongoing (maintenance) therapy, and can be administered intravenously or subcutaneously (under the skin), offering flexibility in treatment. ^{1 2 3 4 5}

What is the purpose of this trial?

Crohn's Disease (CD) is a gastrointestinal disease that can cause chronic diarrhea with or without gross bleeding, abdominal pain, weight loss, and fever. This study will assess the pharmacokinetics, efficacy, and safety of risankizumab in pediatric participants with moderately to severely active CD aged 2 to \< 18 years old who have had intolerance or inadequate response to other therapies. Risankizumab is an approved drug for adults with plaque psoriasis, psoriatic arthritis, and CD and is being developed for the treatment of CD in pediatrics. This study is comprised of 3 cohorts that may participate in 3 substudies (SS). Cohort 1 will enroll participants with ages from 6 to less than 18 years. Cohort 2 will enroll participants with ages from 2 to less than 6 years. Cohort 3 will enroll participants with ages from 2 to less than 18 years. SS1 is an open-label induction period where participants will receive a weight-based induction regimen of risankizumab. SS2 is a double-blind maintenance period where participants will be randomized to receive 1 of 2 doses of weight-based induction regimen of risankizumab. SS3 is an open-label extension period where participants will receive risankizumab based off of their response in SS2. Around 110 pediatric participants with CD will be enrolled at around 100 sites worldwide. Participants in SS1 will receive risankizumab intravenously during the 12-week induction period. Participants in SS2 will receive risankizumab subcutaneously during the 52-week randomized maintenance period. Participants in SS3 will receive risankizumab subcutaneously during the 208-week open label period. Participants will be followed-up for approximately 140 days. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for kids aged 2 to <18 with moderate to severe Crohn's Disease who haven't responded well or can't tolerate other treatments. They need a certain score on a disease activity index and visible inflammation in their guts. Kids with allergies to the drug, different bowel diseases, complications needing surgery, or those who've had too many gut surgeries can't join.

Inclusion Criteria

Must have endoscopic evidence of mucosal inflammation as documented by the SES-CD of ≥ 6 for ileocolonic or colonic disease (or SES-CD of ≥ 4 for isolated ileal disease)

I've had a bad reaction or no improvement from certain gut inflammation treatments.

I am between 2 and 17 years old.

Exclusion Criteria

I have been diagnosed with a form of inflammatory bowel disease.

I am allergic or highly sensitive to the study drug or similar medications.

I was diagnosed with Crohn's disease before I turned 2 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive a weight-based dose of risankizumab intravenously during the 12-week induction period

12 weeks

Regular visits at a hospital or clinic

Maintenance

Participants receive risankizumab subcutaneously during the 52-week randomized maintenance period

52 weeks

Regular visits at a hospital or clinic

Open-label Extension

Participants receive risankizumab subcutaneously during the 208-week open-label period based on their response in the maintenance phase

208 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

Treatment Details

Interventions

• Risankizumab

Trial Overview The study tests Risankizumab, an approved adult drug for psoriasis and arthritis now being tried for pediatric Crohn's Disease. It involves three parts: initial treatment (SS1), comparing two doses (SS2), and long-term follow-up (SS3). The drug will be given through veins first then as shots under the skin.

Participant Groups

Group I: PK Cohort 2: SS3 Dose B Experimental Treatment 1 Intervention

Cohort 2 will enroll participants aged 2 to less than 6 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2.

Group II: PK Cohort 2: SS3 Dose A Experimental Treatment 1 Intervention

Cohort 2 will enroll participants aged 2 to less than 6 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2.

Group III: PK Cohort 2: SS2 Dose B Experimental Treatment 1 Intervention

Cohort 2 will enroll participants aged 2 to less than 6 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3.

Group IV: PK Cohort 2: SS2 Dose A Experimental Treatment 1 Intervention

Cohort 2 will enroll participants aged 2 to less than 6 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose A. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3.

Group V: PK Cohort 2: SS1 Experimental Treatment 1 Intervention

Cohort 2 will enroll participants aged 2 to less than 6 years. SS1 is a 12-week induction period where participants will receive a weight-based dose of risankizumab. All subjects who complete SS1 are eligible to enter SS2.

Group VI: PK Cohort 1: SS3 Dose B Experimental Treatment 1 Intervention

Cohort 1 will consist of 2 age groups (6 to \< 12 years and 12 to \< 18 years). SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2.

Group VII: PK Cohort 1: SS3 Dose A Experimental Treatment 1 Intervention

Cohort 1 will consist of 2 age groups (6 to \< 12 years and 12 to \< 18 years). SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2.

Group VIII: PK Cohort 1: SS2 Dose B Experimental Treatment 1 Intervention

Cohort 1 will consist of 2 age groups (6 to \< 12 years and 12 to \< 18 years). Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3.

Group IX: PK Cohort 1: SS2 Dose A Experimental Treatment 1 Intervention

Cohort 1 will consist of 2 age groups (6 to \< 12 years and 12 to \< 18 years). Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose A. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3.

Group X: PK Cohort 1: SS1 Experimental Treatment 1 Intervention

Cohort 1 will consist of 2 age groups (6 to \< 12 years and 12 to \< 18 years). SS1 is a 12-week induction period where participants will receive a weight-based dose of risankizumab. All subjects who complete SS1 are eligible to enter SS2.

Group XI: Expansion Cohort 3: SS3 Dose B Experimental Treatment 1 Intervention

Cohort 3 will enroll participants aged 2 to less than 18 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2.

Group XII: Expansion Cohort 3: SS3 Dose A Experimental Treatment 1 Intervention

Cohort 3 will enroll participants aged 2 to less than 18 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2.

Group XIII: Expansion Cohort 3: SS2 Dose B Experimental Treatment 1 Intervention

Cohort 3 will enroll participants aged 2 to less than 18 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive either double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3.

Group XIV: Expansion Cohort 3: SS2 Dose A Experimental Treatment 1 Intervention

Cohort 3 will enroll participants aged 2 to less than 18 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive either double-blind risankizumab Dose A. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3.

Group XV: Expansion Cohort 3: SS1 Experimental Treatment 1 Intervention

Cohort 3 will enroll participants aged 2 to less than 18 years. SS1 is a 12-week induction period where participants will receive a weight-based dose of risankizumab. All subjects who complete SS1 are eligible to enter SS2.

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]

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]

Subcutaneous risankizumab, a selective anti-IL-23 antibody, has been shown to be an effective maintenance therapy for patients with moderately to severely active Crohn's disease, achieving higher rates of clinical remission and endoscopic response compared to placebo in a study involving 542 participants.

The treatment was well tolerated, with adverse event rates similar across all groups, indicating that risankizumab could be a safe new option for patients who need ongoing management of their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Ferrante, M., Panaccione, R., Baert, F., et al.[2022]

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 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]

In a study involving 198 Asian patients with moderate-to-severe Crohn's disease, risankizumab demonstrated significant efficacy, with 61.4% achieving clinical remission and 40.0% showing endoscopic response at week 12, compared to placebo.

In the maintenance phase, 75.0% of patients receiving the higher dose of risankizumab (360 mg) achieved clinical remission at week 52, indicating that risankizumab is both effective and well tolerated in Asian patients, similar to results seen in non-Asian populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of risankizumab for Crohn's disease in patients from Asian countries: a post hoc subanalysis of the global phase 3 ADVANCE, MOTIVATE, and FORTIFY studies. Gao, X., Fujii, T., Ye, BD., et al.[2023]

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

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

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

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. [2022]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. 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]

7. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and safety of risankizumab for Crohn's disease in patients from Asian countries: a post hoc subanalysis of the global phase 3 ADVANCE, MOTIVATE, and FORTIFY studies. [2023]