Ustekinumab for Pediatric Crohn's Disease

(UNITI Jr Trial)

Recruiting at 70 trial locations

Overseen By Study Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Symptomatic strictures, Malignancy, Liver insufficiency, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

101 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

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.

What data supports the effectiveness of the drug ustekinumab for pediatric Crohn's disease?

Research shows that ustekinumab, a drug used for Crohn's disease, led to clinical remission in about 50% of patients after one year. Additionally, a 10-year-old girl with Crohn's disease achieved remission without adverse effects after using ustekinumab, suggesting it may be effective and safe for children. ^{1 2 3 4 5}

Is ustekinumab safe for children with Crohn's disease?

Ustekinumab has been used in children with Crohn's disease, and studies have shown it to be generally safe, with no serious side effects like infusion reactions or increased infections reported in some cases. ^{1 2 3 4 6}

How is the drug ustekinumab unique for treating pediatric Crohn's disease?

Ustekinumab is unique because it targets specific proteins (interleukin-12 and interleukin-23) involved in inflammation, offering a different approach than traditional treatments like corticosteroids or TNF antagonists. It is administered as an intravenous induction followed by subcutaneous maintenance, and has shown promise in children who have not responded to other treatments. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial is testing a medication that reduces inflammation in children with severe Crohn's disease. The goal is to see if it can help them get better and stay better. The study will also check how safe the medication is and how it works in the body.

Research Team

Janssen Research & Development, LLC 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 endoscopy and histology. They must have a PCDAI score >30 and show ulceration or elevated CRP/fecal calprotectin levels. Girls who can have babies must test negative for pregnancy. Kids with certain infections, recent investigational drug use, Crohn's complications that might need surgery, cancer history, or serious organ problems can't join.

Inclusion Criteria

I am a woman who can have children and have tested negative for pregnancy.

I have Crohn's disease with active inflammation, confirmed by a past endoscopy.

I have active Crohn's disease with a recent test showing ulcers in my intestines.

Exclusion Criteria

I do not have severe ongoing issues with my liver, kidneys, heart, lungs, or other major systems.

I have or had cancer or symptoms that might suggest blood cancer.

I have had infections like histoplasmosis or similar conditions before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

All participants receive a single IV administration of ustekinumab based on body surface area or weight-tiered induction dose

8 weeks

1 visit (in-person)

Maintenance

Participants receive SC administration of ustekinumab every 8 or 12 weeks based on BSA or weight-tiered induction dose

44 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Ustekinumab

Trial Overview The study tests Ustekinumab in kids to see if it helps them reach and maintain remission from Crohn's symptoms compared to a placebo (a treatment with no active drug). It also looks at the safety of the drug and how it moves through and out of their bodies over time.

Participant Groups

Group I: Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period Experimental Treatment 2 Interventions

Participants will receive SC administration of ustekinumab q8w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at maintenance weeks (Weeks M)-0, M-8, M-16, M-24, M 32, and M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind.

Group II: Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period Experimental Treatment 2 Interventions

Participants will receive SC administration of ustekinumab q12w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-12, M-24, M-36 and matching placebo at Weeks M-8, M-16, M-32, and M-40 to maintain the blind.

Group III: Open- Label Ustekinumab Intravenous (IV): Induction Period Experimental Treatment 1 Intervention

All participants will receive a single IV administration of ustekinumab at induction Week 0 (I-0) based on body surface area (BSA) (milligram per meter square \[mg/m\^2\]) or weight-tiered induction dose (milligram per kilogram \[mg/kg\]).

Ustekinumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Stelara for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Approved in United States as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Canada as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Japan as Stelara for:

• Plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

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

In a study of 36 adults with Crohn's disease, 61% responded to ustekinumab treatment after one year, but no distinct gene expression signature was found to predict response, indicating that more research is needed to identify reliable biomarkers.

Among nonresponders, an increased inflammatory response was observed, with 68 genes linked to cytokine activity and chemokine receptor binding, suggesting that these pathways may play a role in treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. Granot, M., Braun, T., Efroni, G., et al.[2023]

In a Phase 1 study involving 44 children with moderately to severely active Crohn's disease, ustekinumab showed pharmacokinetics similar to adults, but lower serum levels were observed in patients weighing less than 40 kg, indicating a need for adjusted dosing in this group.

The study found that 22% of patients on the lower dose and 29% on the higher dose achieved clinical remission by Week 16, with a notable 73% reporting at least one adverse event, suggesting that while ustekinumab is generally safe, careful monitoring is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study. Rosh, JR., Turner, D., Griffiths, A., et al.[2022]

Ustekinumab was effective in achieving clinical and endoscopic remission in a 10-year-old girl with Crohn's disease after 75 weeks of treatment, indicating its potential as a first-line biological agent for pediatric patients.

The treatment was well-tolerated with no reported adverse events, suggesting that ustekinumab is a safe option for managing pediatric inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab as the First Biological Agent for Crohn's Disease in a 10-Year-Old Girl. Fujita, Y., Sugaya, T., Tanaka, T., et al.[2021]

In a small study of 4 adolescent patients with pediatric Crohn disease, ustekinumab was administered after they had not responded to multiple other treatments, including corticosteroids and other biologics.

Out of the 4 patients, 2 showed a clinical response to ustekinumab, while the other 2 had to discontinue due to ongoing symptoms and complications, highlighting the need for further research to assess the drug's efficacy and safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab in Pediatric Crohn Disease Patients. Bishop, C., Simon, H., Suskind, D., et al.[2022]

In a study of 463 Crohn's disease patients treated with ustekinumab for at least 6 months, 56% achieved remission and 70% had a positive response by week 16, demonstrating its effectiveness in real-world settings.

Ustekinumab was found to be safe for long-term use, with an 18% discontinuation rate per patient-year and only 8.4% of patients reporting adverse events, indicating a favorable safety profile in a refractory patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study. Chaparro, M., Baston-Rey, I., Fernández-Salgado, E., et al.[2022]

In a systematic review of 11 studies involving 370 pediatric patients with inflammatory bowel disease (IBD), ustekinumab showed that about 46% of children with Crohn's disease achieved clinical remission after one year, indicating its potential efficacy in this population.

Ustekinumab demonstrated a reasonable safety profile, with serious adverse events occurring in only 3.5% of patients, although dose adjustments were often necessary for continued treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Ustekinumab for Pediatric Inflammatory Bowel Disease: A Systematic Review. Fang, S., Zhang, S., Zhang, C., et al.[2023]

Ustekinumab is an effective treatment for adults with moderately to severely active Crohn's disease who have not responded to or are intolerant of other therapies, showing improved clinical response and remission rates in pivotal phase III trials.

The drug has a unique mechanism of action targeting IL-12 and IL-23 cytokines, and it is generally well tolerated, with serious side effects like infections and malignancies being rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. Lamb, YN., Duggan, ST.[2018]

References

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

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Ustekinumab as the First Biological Agent for Crohn's Disease in a 10-Year-Old Girl. [2021]

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

Ustekinumab in Pediatric Crohn Disease Patients. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Ustekinumab for Pediatric Inflammatory Bowel Disease: A Systematic Review. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. [2018]