Risankizumab for Pediatric Crohn's Disease

(RISE Trial)

Recruiting at 121 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

118 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of risankizumab (Skyrizi) for children with Crohn's Disease (CD), which can cause chronic diarrhea, abdominal pain, and weight loss. The study aims to determine if risankizumab, already used in adults for similar conditions, can benefit children who haven't responded well to other treatments. Participants will be divided into age-based groups and receive different doses over an extended period. Children with moderate to severe CD who haven't found relief with other medications might be suitable for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants early access to a potentially effective treatment.

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.

Is there any evidence suggesting that risankizumab is likely to be safe for pediatric patients with Crohn's Disease?

Research has shown that risankizumab is safe for treating Crohn's disease (CD) in children. Early findings suggest it helps children with severe CD improve significantly, with symptoms either greatly improving or disappearing.

In adults, risankizumab is already approved for conditions like plaque psoriasis and psoriatic arthritis, indicating its safety. Studies have demonstrated that risankizumab is effective and safe for adults with moderate-to-severe CD, making it a promising option for children as well.

The treatment is generally well-tolerated, with no unexpected safety issues reported, meaning most people do not experience serious side effects. However, like any treatment, it may still cause some side effects, so regular check-ups and monitoring are important during the trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Crohn's Disease?

Researchers are excited about risankizumab for pediatric Crohn's disease because it offers a targeted approach by inhibiting interleukin-23 (IL-23), a protein involved in inflammatory processes. Unlike standard treatments like corticosteroids and immunosuppressants, which broadly suppress the immune system, risankizumab specifically targets the pathway responsible for inflammation in Crohn's. This precision could mean fewer side effects and potentially more effective control of the disease. Additionally, risankizumab is administered as an injection, which might offer convenience compared to some other treatment regimens.

What evidence suggests that risankizumab might be an effective treatment for pediatric Crohn's disease?

Research has shown that risankizumab effectively treats Crohn's Disease in both adults and children. One study found that after three doses, 65% of children experienced a lasting reduction in bowel symptoms, and 70% had no disease symptoms at all. Additionally, 74% of these children responded well to the treatment. This trial will evaluate different dosing regimens of risankizumab in pediatric participants. Risankizumab works by blocking a specific protein that causes inflammation, helping to reduce Crohn's Disease symptoms. This medication is already approved for adults with Crohn's Disease, psoriasis, and psoriatic arthritis, demonstrating its effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 (including Sub-cohort 1A) 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 (including Sub-cohort 1A) 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 (including Sub-cohort 1A) 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 (including Sub-cohort 1A) 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 (including Sub-cohort 1A) 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 participants 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

Published Research Related to This Trial

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]

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]

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]

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 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 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]

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]

Citations

1. academic.oup.com academic.oup.com/ecco-jcc/article/18/Supplement_1/i1435/7586842

P775 Efficacy and safety of risankizumab in children with ... After 3 infusions, SFR was observed in 15 (65%) children, clinical remission in 16 (70%), clinical response in 17 (74%), and CRP remission in 17 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11287916/

Positioning risankizumab in the treatment algorithm of ... For the second primary and all secondary end points Risankizumab demonstrated superiority, with a p-value of <0.0001 versus ustekinumab; endoscopic remission ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05995353

NCT05995353 | A Study to Assess Adverse Events, ... This study will assess the pharmacokinetics, efficacy, and safety of risankizumab in pediatric participants with moderately to severely active CD aged 2 to < 18 ...

5. eposters.ddw.org eposters.ddw.org/ddw/2024/ddw-2024/413886/elizabeth.spencer.effectiveness.and.safety.of.risankizumab.in.children.with.html?f=listing%3D3%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D2%2Aspeaker%3D852621

effectiveness and safety of risankizumab in children with ... Risankizumab (RZB) is a selective p19 anti-interleukin (IL)-23 antibody approved for adults with Crohn's disease (CD) and for children ≥ 16 ...

6. 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 ... Examining the real-world effectiveness and safety of risankizumab in patients with Crohn's disease. Interleukin 23 (IL-23) is a cytokine that ...