Risankizumab for Crohn's Disease

(AFFIRM Trial)

Recruiting at 165 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

276 Participants Needed

Trial Summary

What is the purpose of this trial?

Crohn's disease (CD) is a long-lasting disease that causes severe inflammation (redness, swelling), in the digestive tract, most often affecting the bowels. It can cause many different symptoms including abdominal pain, diarrhea, tiredness, and weight loss. This study will assess how safe and effective risankizumab subcutaneous (SC) induction treatment is in treating moderately to severely active CD in adult participants. Risankizumab is an approved drug for adults with CD. This study comprises of a Period A, a Period B, and a Period C. In Period A, participants are placed in 1 of 2 groups to receive either risankizumab SC Dose A or Placebo. In Period B, based on response, participants will receive risankizumab SC Dose B or Placebo. Participants who do not have improvement in CD symptoms at Week 12 will receive risankizumab SC Dose C and participants with worsening CD symptoms in period B will receive risankizumab SC. In Period C, eligible participants will receive open-label risankizumab SC Dose D. Approximately 276 adult participants with a diagnosis of moderately to severely active CD will be enrolled in approximately 250 sites globally. Participants will receive SC induction treatment of risankizumab or matching placebo for up to 24 weeks in Period A and B followed by an open-label risankizumab extension in Period C for 52 weeks. The duration of the study will be approximately 93 weeks.

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.

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

Research shows that Risankizumab, a drug that targets a specific part of the immune system, helped people with Crohn's Disease achieve clinical remission (symptom relief) and improved gut health in several studies. It was effective both as an initial treatment and for long-term maintenance. ^{1 2 3 4 5}

Is risankizumab safe for humans?

Risankizumab has been shown to have acceptable safety in clinical trials for Crohn's disease, with studies evaluating its long-term safety and real-world adverse events. It is also approved for treating plaque psoriasis, indicating its general safety in humans. ^{1 2 4 6 7}

How is the drug Risankizumab different from other treatments for Crohn's disease?

Risankizumab is unique because it targets interleukin-23 (IL-23), a protein involved in inflammation, and is used both as an induction and maintenance therapy for Crohn's disease. It is administered intravenously for induction and subcutaneously for maintenance, offering a novel approach compared to other treatments. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. 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]

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

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

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

In active Crohn disease, risankizumab increased clinical remission and endoscopic response at 12 wk. [2022]

4. 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]

5. 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]

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse events with risankizumab in the real world: postmarketing pharmacovigilance assessment of the FDA adverse event reporting system. [2023]