Risankizumab for Crohn's Disease

(AFFIRM Trial)

Not currently recruiting at 222 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: P19 inhibitors

Disqualifiers: Ulcerative colitis, Indeterminate colitis, 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 effectiveness and safety of risankizumab (also known as Skyrizi), a treatment for Crohn's disease, which causes inflammation in the digestive tract and symptoms like stomach pain and diarrhea. Participants will receive varying doses of the drug or a placebo (a treatment with no active medication) to evaluate its effectiveness over time. The trial is ideal for adults with moderate to severe Crohn's disease who have not found relief with other treatments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants with unstable doses of their Crohn's disease therapy are excluded. This might mean that you need to be on a stable dose of your current medication to participate.

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

Research has shown that risankizumab is generally well-tolerated by people with Crohn's disease. In studies, the most common side effects were mild, including colds, headaches, and joint pain. These side effects appeared both at the start of treatment and during ongoing use.

Long-term use of risankizumab, administered every 8 weeks, did not reveal any new safety issues. This indicates that people did not experience unexpected or serious problems from taking the drug over time. While some side effects occur, they are usually not severe, and many people handle the treatment well. ^{1 2 3 4 5}

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

Unlike the standard treatments for Crohn's disease, which often include corticosteroids, immunosuppressants, and biologics like TNF inhibitors, risankizumab works by targeting a different pathway. Risankizumab is a monoclonal antibody that specifically inhibits IL-23, a protein involved in inflammatory processes. This unique mechanism of action might offer a new option for patients who have not responded well to other treatments. Additionally, risankizumab is administered via subcutaneous injection, which can be more convenient than intravenous options. Researchers are excited about the potential for risankizumab to provide more effective and targeted relief for those with Crohn's disease.

What is the effectiveness track record for risankizumab in treating Crohn's disease?

Research has shown that risankizumab effectively treats Crohn's disease. In studies, about 59% of patients were symptom-free after three months, with some remaining symptom-free at six and twelve months. Real-world data indicates that 58.2% of patients improved without needing steroids. Additionally, long-term studies suggest risankizumab is both effective and safe for people with Crohn's disease. Overall, these findings support using risankizumab to help manage symptoms of this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with moderately to severely active Crohn's Disease who haven't responded well to other treatments can join this study. They must have a confirmed diagnosis for at least 3 months and show clear signs of inflammation in their bowels.

Inclusion Criteria

My Crohn's disease hasn't improved with standard or advanced treatments.

You have been determined to exhibit moderate-to-severe Crohn's Disease (CD) according to a comprehensive assessment instrument.

You have had a diagnosis of Crohn's Disease verified by biopsy for at least three months prior to the start of this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period A

Participants receive risankizumab Dose A or placebo for up to 12 weeks

12 weeks

Regular visits for monitoring and administration

Treatment Period B

Based on response, participants receive risankizumab Dose B or placebo for up to 12 weeks. Participants with inadequate response receive Dose C

12 weeks

Regular visits for monitoring and administration

Open-label Extension Period C

Eligible participants receive open-label risankizumab Dose D for 52 weeks

52 weeks

Regular visits for monitoring and administration

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 is testing Risankizumab, an approved drug for Crohn's Disease, given as a subcutaneous injection. Participants are randomly assigned to get either the real drug or a placebo during two periods, totaling about 49 weeks.

How Is the Trial Designed?

Group I: Period C: Open-Label Risankizumab Dose D Experimental Treatment 1 Intervention

Participants who complete the Period B Week 24 visit to receive open-label risankizumab Dose D administered by subcutaneous (SC) injection for up to 52 weeks during Period C.

Group II: Period B: Risankizumab Dose C Experimental Treatment 1 Intervention

Participants with inadequate response in Period A to receive Dose C administered by Subcutaneous (SC) injection for up to 12 weeks during Period B.

Group III: Period B: Risankizumab Dose B Experimental Treatment 1 Intervention

Participants randomized to receive risankizumab Dose A in Period A that achieved adequate response to receive risankizumab Dose B administered by subcutaneous (SC) injection for up to 12 weeks.

Group IV: Period A: Risankizumab Dose A Experimental Treatment 1 Intervention

Participants randomized to receive risankizumab Dose A administered by subcutaneous (SC) injection for up to 12 weeks during Period A.

Group V: Period B: Placebo Placebo Group 1 Intervention

Participants randomized to receive placebo risankizumab in Period A that achieved adequate response to continue to receive placebo for risankizumab administered by Subcutaneous (SC) injection for up to 12 weeks in Period B.

Group VI: Period A: Placebo Placebo Group 1 Intervention

Participants randomized to receive placebo for risankizumab administered by Subcutaneous (SC) injection for up to 12 weeks during Period A.

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 was evaluated as an induction therapy for Crohn's disease in two phase 3 trials (ADVANCE and MOTIVATE), demonstrating significant efficacy in achieving clinical remission among participants.

The results indicated that risankizumab effectively reduced disease activity in patients with Crohn's disease, suggesting it could be a promising treatment option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In active Crohn disease, risankizumab increased clinical remission and endoscopic response at 12 wk. Oliver, D., Talley, NJ.[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]

In a large analysis of 10,235 reports from the FDA Adverse Event Reporting System, risankizumab was associated with 161 adverse events (AEs), including unexpected ones like myocardial infarction and pancreatitis, highlighting the need for careful monitoring.

The study identified that most AEs related to risankizumab were reported as serious, with a significant number of cases showing a gradual decrease in reported AEs over time, suggesting that the risks may diminish with continued use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events with risankizumab in the real world: postmarketing pharmacovigilance assessment of the FDA adverse event reporting system. Shu, Y., Chen, J., Ding, Y., et al.[2023]

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]

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]

Citations

1. 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.1. aContinuous placebo ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40857638/

Long-term Outcomes of Patients with Crohn's Disease ... Background: Cumulative data suggest that risankizumab is an effective and safe treatment for patients with Crohn's disease (CD).

3. 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 ... Researchers shared real-world effectiveness data and demonstrated how RZB performs in patients with prior therapy exposure and other ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38215029/

Real-world Effectiveness and Safety of Risankizumab in ... In this real-world study of multirefractory Crohn's disease patients, risankizumab was effective, with 58.2% and 27.3% achieving steroid-free clinical response ...

5. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1586/7967969

P0832 Real-world effectiveness of risankizumab in Crohn's ... Rates of clinical remission were 59% (211/358), 50% (77/154), and 44% (14/32) at 3, 6 and 12 months. Rates of clinical remission for ustekinumab ...

6. skyrizihcp.com skyrizihcp.com/gastroenterology/crohns-disease/safety

Safety Profile - SKYRIZI® (risankizumab-rzaa) for Crohn's Most common (>3%) adverse reactions associated with SKYRIZI in Crohn's disease are upper respiratory infections, headache, and arthralgia in induction and ...

7. skyrizi.com skyrizi.com/crohns

take control of your crohn's with skyrizi 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. va.gov va.gov/formularyadvisor/DOC_PDF/MON_Risankizumab-rzaa_SKYRIZI_in_Crohns_Disease_Monograph_Mar_2023.pdf

Risankizumab-rzaa (SKYRIZI) in Crohn's Disease National ... Safety Results from Clinical Trials: • Table 5 summarizes selected safety data from the phase 3 clinical trials. Page 4. Risankizumab-rzaa in CD Monograph. 4.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8684487/

Long-Term Safety and Efficacy of Risankizumab Treatment in ... Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn's disease, with no new safety ...

10. 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 ...