Guselkumab for Pediatric Crohn's Disease

(MACARONI-23 Trial)

Recruiting at 137 trial locations

Overseen By Study Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Symptomatic strictures, Abscess, Recent surgery, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests guselkumab, a treatment for children and teens with Crohn's disease, which causes painful inflammation in the digestive tract. The study aims to evaluate the drug's effectiveness in reducing symptoms and improving the gut's appearance after a year of treatment. Participants will initially receive guselkumab through an IV or injection for 12 weeks. Those who respond well will continue with different injection doses for another 48 weeks. Suitable candidates have active Crohn's disease and have not responded well to other treatments like steroids or biologics. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new 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 guselkumab is likely to be safe for pediatric patients with Crohn's Disease?

Research shows that guselkumab, also known as TREMFYA®, is generally well-tolerated in people with Crohn's Disease. Common side effects include allergic reactions, dizziness, and infections, though serious side effects are rare. Studies have found that guselkumab leads to high rates of symptom relief, with over 85% of patients remaining symptom-free for 96 weeks. This suggests the treatment is effective and relatively safe for most people.

It's important to note that while this data is promising, this trial specifically focuses on children with Crohn's Disease. Although guselkumab is being tested in children, most current safety information comes from adults. If the treatment is approved for other conditions, like ulcerative colitis, this can provide some reassurance about its safety. However, discussing any concerns with a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's Disease?

Researchers are excited about guselkumab for pediatric Crohn's disease because it offers a novel approach by targeting interleukin-23 (IL-23), a specific protein involved in inflammatory pathways. Unlike standard treatments like corticosteroids and TNF inhibitors, which have broader effects on the immune system, guselkumab's focus on IL-23 may lead to more precise inflammation control with potentially fewer side effects. Additionally, guselkumab provides flexible administration options, including both intravenous (IV) and subcutaneous (SC) routes, allowing for tailored treatment plans based on patient needs. This combination of a targeted mechanism and versatile delivery makes guselkumab a promising candidate in managing Crohn's disease in children.

What evidence suggests that guselkumab might be an effective treatment for Crohn's Disease?

Research has shown that guselkumab holds promise for treating Crohn's disease. In earlier studies, more than 85% of patients experienced symptom relief after 96 weeks of guselkumab use. Specifically, 42% of patients on a particular dose experienced both symptom relief and improved intestinal appearance after one year. The treatment blocks IL-23, a protein that causes inflammation, a major issue in Crohn's disease. This trial will explore different dosing regimens of guselkumab, including intravenous and subcutaneous administration, to determine its effectiveness in managing symptoms and improving intestinal health in children with Crohn's disease. ^{1 3 4 5 6}

Who Is on the Research Team?

Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for children with moderately to severely active Crohn's Disease, confirmed by clinical and endoscopic criteria. They must have a PCDAI score >30 and an SES-CD score >=6 (or >=4 for isolated ileal disease). Participants should have tried other treatments without success or could not tolerate them. Those who've had recent bowel surgery or have complications like abscesses or strictures can't join.

Inclusion Criteria

I have Crohn's disease and treatments like immunomodulators, steroids, or biologics/JAK inhibitors haven't worked well for me.

I have been diagnosed with Crohn's Disease or fistulizing Crohn's Disease.

My Crohn's disease is moderate to severe.

Exclusion Criteria

I do not have an abscess.

I haven't had bowel surgery in the last 6 months or any abdominal surgery in the last 3 months.

I have Crohn's disease with complications that may need surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive guselkumab intravenously or subcutaneously based on their body weight during the 12-week open-label induction phase

12 weeks

Maintenance

Week 12 responders are randomized into a double-blind maintenance phase to receive guselkumab SC dose regimen based on their body weight up to Week 48

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guselkumab

Trial Overview

The study tests the effectiveness of Guselkumab, a medication, in treating Crohn's Disease in kids over one year. It checks if those who responded well at Week 12 continue to benefit at Week 52. The trial includes a comparison group receiving a placebo to measure Guselkumab's true effects.

How Is the Trial Designed?

Group I: Open-label maintenance phase: Guselkumab SC Experimental Treatment 1 Intervention

Week 12 non-responders will not be randomized and will enter an open-label maintenance phase to receive guselkumab SC dosing regimen based on their body weight up to Week 48.

Group II: Open-label induction phase: Guselkumab Subcutaneously (SC) Experimental Treatment 1 Intervention

Participants will receive guselkumab dose SC based on their body weight during the 12-week open-label induction phase.

Group III: Open-label induction phase: Guselkumab Intravenously (IV) Experimental Treatment 1 Intervention

Participants will receive guselkumab dose IV based on their body weight during the 12-week open-label induction phase.

Group IV: Double-blind maintenance phase: Guselkumab SC Dose Regimen 1 Experimental Treatment 1 Intervention

At the end of the induction phase, Week 12 responders will be randomized into the double-blind maintenance phase to receive guselkumab dose regimen 1 SC based on their body weight up to Week 48.

Group V: Double-blind Maintenance Phase: Guselkumab SC Dose Regimen 2 Experimental Treatment 1 Intervention

At the end of the induction phase, Week 12 responders will be randomized into the double-blind maintenance phase to receive guselkumab dose regimen 2 SC based on their body weight up to Week 48.

Guselkumab is already approved in United States, European Union for the following indications:

Approved in United States as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Approved in European Union as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

A 12-year-old boy with infliximab-resistant Crohn's disease, including active perianal fistulas, was successfully treated with adalimumab, leading to significant improvement in his condition after 10 weeks.

Adalimumab not only normalized the patient's disease activity index but also closed the fistulas and significantly enhanced his quality of life, suggesting it is a viable treatment option for pediatric patients who do not respond to infliximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adalimumab treatment in infliximab-resistant pediatric patient with Crohn's disease]. Veres, G., Putz, R., Szabó, D., et al.[2022]

In a study of 10 pediatric patients with Crohn's disease who had previously failed infliximab treatment, adalimumab showed a clinical response in 80% of patients after 1 month and 71% after 1 year, indicating its efficacy as a subsequent treatment option.

The treatment was well-tolerated, with no serious adverse events reported, suggesting that adalimumab is a safe option for managing pediatric-onset Crohn's disease in patients who did not respond to infliximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab Treatment in Pediatric-Onset Crohn's Disease Patients after Infliximab Failure: A Single Center Study. Song, WJ., Kang, B., Choi, SY., et al.[2020]

In a study of 10 pediatric patients with Crohn's disease who were resistant to anti-TNF treatments, 7 required more frequent dosing of ustekinumab (every 4-6 weeks) to achieve a clinical response or remission.

Therapeutic drug monitoring revealed that many patients had low drug levels on standard dosing, indicating that adjusting the dosing interval may be necessary for effective treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmented ustekinumab dosing is needed to achieve clinical response in patients with anti-TNF refractory pediatric Crohn's disease: a retrospective chart review. Do, P., Andersen, J., Patel, A., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT05923073

NCT05923073 | A Study of Guselkumab in Pediatric ...

The purpose of this study is to evaluate the clinical and endoscopic efficacy of guselkumab in pediatric participants with Crohn's Disease (CD) at the end ...

2.

jnjmedicalconnect.com

jnjmedicalconnect.com/products/tremfya/medical-content/tremfya-use-in-pediatric-patients-with-ulcerative-colitis-or-crohns-disease

TREMFYA – Use in Pediatric Patients with Ulcerative ...

Crohn's disease (MACARONI-23): The clinical and endoscopic efficacy of TREMFYA is currently being evaluated in pediatric patients (ages 2-17 ...

3.

jnj.com

jnj.com/media-center/press-releases/tremfya-guselkumab-the-first-and-only-il-23-inhibitor-with-a-fully-subcutaneous-treatment-regimen-demonstrates-durable-remission-in-crohns-disease-at-two-years

TREMFYA® (guselkumab), the first and only IL-23 inhibitor ...

Clinical remission rates were over 85% for both TREMFYA® maintenance doses at 96 weeks in both the Phase 3 GRAVITI and GALAXI studies

4.

tremfya.com

tremfya.com/crohns-disease/results/

Crohn's Disease (CD): Results & Safety

Also, 42% of patients on TREMFYA ® 100 mg SC maintenance doses achieved clinical remission and endoscopic response † at 1 year. Patients who achievedvisible

5.

mountsinai.org

mountsinai.org/about/newsroom/2025/guselkumab-demonstrates-superior-efficacy-in-landmark-clinical-trials-and-offers-new-hope-to-crohns-disease-patients

Guselkumab Demonstrates Superior Efficacy in Landmark ...

Guselkumab demonstrated statistically significant improvements across multiple endpoints, including endoscopic response and deep remission.

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2025/761061s024lbl.pdf

Reference ID: 5553897 - accessdata.fda.gov

The apparent clearance in subjects with Crohn's disease was 0.568 L/day. Mean half-life of guselkumab was approximately 17 days in subjects with Crohn's disease ...