Guselkumab for Pediatric Crohn's Disease

(MACARONI-23 Trial)

Recruiting at108 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Symptomatic strictures, Abscess, Recent surgery, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests guselkumab, an anti-inflammatory medication, on children with Crohn's Disease who initially responded well to it. The goal is to see if the benefits last over several months by reducing immune system activity. Guselkumab has shown effectiveness in treating moderate-to-severe psoriasis and psoriatic arthritis.

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

Guselkumab is unique because it targets interleukin 23, a specific protein involved in inflammation, which is different from other treatments like infliximab and adalimumab that target tumor necrosis factor alpha (TNF-alpha). This different mechanism of action may offer an alternative for patients who do not respond to existing anti-TNF therapies. ^{1 2 3}

Research Team

Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Guselkumab (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

[Adalimumab treatment in infliximab-resistant pediatric patient with Crohn's disease]. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Adalimumab Treatment in Pediatric-Onset Crohn's Disease Patients after Infliximab Failure: A Single Center Study. [2020]

3. England 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. [2021]