Long-Term Ustekinumab for Pediatric Crohn's Disease

(UNITED Trial)

Recruiting at 70 trial locations

Overseen By Study Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Ustekinumab

Disqualifiers: Pregnancy, COVID-19, 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: Unknown

Duration: Up to 6 years and 4 months

151 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the long-term safety of ustekinumab, a medication for pediatric Crohn's disease, a chronic condition causing inflammation in the digestive tract. Participants will continue receiving ustekinumab, and researchers will monitor their health to ensure the treatment remains safe over time. To qualify, children must have completed a previous ustekinumab study and shown benefits, such as improved symptoms or remission. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of this treatment for wider use.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that any disallowed therapies noted in the primary study should not be taken before the first dose in this study. It's best to discuss your current medications with the study team.

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

Research has shown that ustekinumab is generally well-tolerated by children with Crohn's disease. In past studies, about 22% to 52% of children became symptom-free at various times, such as weeks 8 and 16. This indicates that while responses vary, the treatment can be effective for some.

Importantly, the FDA has already approved ustekinumab for other conditions, indicating it has undergone safety studies in people. Although side effects can occur, serious ones are uncommon. This ongoing study aims to gather more information on long-term safety, continuing to examine the treatment's safety over time. ^{1 2 3 4 5}

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

Ustekinumab is unique because it targets a specific part of the immune system known as interleukin-12 and interleukin-23 (IL-12 and IL-23), which are proteins involved in inflammation. Unlike traditional treatments for pediatric Crohn's disease, such as corticosteroids or immunosuppressants that broadly suppress the immune system, ustekinumab offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about ustekinumab because it has shown promise in maintaining remission in Crohn's disease with less frequent dosing, which can improve the quality of life for young patients by reducing the need for frequent medication administration.

What evidence suggests that ustekinumab is effective for pediatric Crohn's disease?

Research has shown that ustekinumab, the treatment under study in this trial, effectively treats Crohn's disease in children. One study found that nearly 80% of children stopped using steroids while maintaining symptom control after one year on ustekinumab. Another study reported that about 42% of children were symptom-free between weeks 24 to 32. Long-term research indicates that ustekinumab helps maintain symptom control and heals the gut lining. Overall, these findings suggest that ustekinumab is a promising option for managing Crohn's disease in young patients. ^{1 3 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for pediatric patients who have completed a primary ustekinumab study for Crohn's Disease, Psoriatic Arthritis, or Ulcerative Colitis. They must show benefits from previous treatment and agree to lifestyle restrictions. Girls must not be pregnant and all participants should not plan on becoming parents soon.

Inclusion Criteria

My condition improved with ustekinumab as shown in my last study visit.

I am capable of becoming pregnant and have a negative pregnancy test.

I have finished all my ustekinumab treatments as planned in a previous study.

Exclusion Criteria

I have or was in close contact with someone who has COVID-19.

I may have received a live vaccine but can stay in the study if the sponsor agrees and I pause the study treatment for a time they specify.

Pregnant, nursing, or planning pregnancy or fathering a child

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ustekinumab with dosing regimens based on their previous study participation

Up to 6 years and 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive ustekinumab in an open-label format for long-term safety data collection

Up to 6 years and 4 months

What Are the Treatments Tested in This Trial?

Interventions

• Ustekinumab

Trial Overview The trial is testing the long-term safety of ustekinumab, an injectable medication given under the skin (subcutaneous), in children who have shown improvement with this drug during a prior study.

How Is the Trial Designed?

Group I: Ustekinumab Experimental Treatment 1 Intervention

Participants will have continued access to ustekinumab for primary study (CNTO1275CRD1001, CNTO1275PUC3001, CNTO1275CRD3004, CNTO1275JPA3001) participants who in the opinion of the investigator will continue to benefit from ustekinumab therapy. All blinded participants who enroll in the long-term extension (LTE) from blinded primary studies with both every 8 weeks (q8w) and every 12 weeks (q12w) dosing groups just prior to the end of the primary study will be assigned to the q8w dosing regimen. Participants enrolling in the LTE from an unblinded primary study will remain on the final dosing regimen that they were receiving in the primary study. Participants enrolling from the Exposure Optimization Substudy may be eligible to remain on the every 4 weeks (q4w) dosing regimen.

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+

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

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]

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]

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]

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]

Ustekinumab is equally effective in treating Crohn's disease in elderly patients (over 60 years) compared to younger patients, with similar rates of steroid-free remission at various follow-up points (16, 32, and 54 weeks).

The safety profile of ustekinumab is generally comparable between elderly and younger patients, although there is a higher incidence of new cancers (de novo neoplasms) in older patients, which may be linked to their age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry. Casas-Deza, D., Lamuela-Calvo, LJ., Gomollón, F., et al.[2023]

A study involving 117 Crohn's disease patients, including 39 elderly (≥65 years) and 78 nonelderly (<65 years), found that ustekinumab (UST) is safe and effective for treating elderly patients, with nearly 90% experiencing a clinical response.

Elderly patients were less likely to achieve complete clinical remission compared to nonelderly patients (28.2% vs. 52.6%), but there were no significant differences in adverse events or complications between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. Garg, R., Aggarwal, M., Butler, R., et al.[2023]

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]

In a study of 52 pediatric patients with inflammatory bowel disease (IBD) treated with ustekinumab, 50% of those previously exposed to biologics and 90% of biologic-naïve patients achieved steroid-free remission after 52 weeks, indicating its effectiveness in this age group.

The treatment was found to be safe, with only two infusion reactions reported and no serious adverse events or infections, suggesting a favorable safety profile for ustekinumab in children and young adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Experience With Ustekinumab in Children and Young Adults at a Tertiary Care Pediatric Inflammatory Bowel Disease Center. Dayan, JR., Dolinger, M., Benkov, K., et al.[2023]

In a study of 122 Crohn's disease patients treated with ustekinumab, 72% showed a clinical response, and over 50% continued treatment for more than 2 years without losing effectiveness or needing surgery.

Ustekinumab demonstrated a good safety profile, with a 55% persistence rate at 36 months, although only one severe adverse event (anal adenocarcinoma) was reported, indicating it is a viable long-term treatment option for anti-TNF refractory patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience. Wils, P., Bouhnik, Y., Michetti, P., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39888083/

Ustekinumab is safe and effective in pediatric patients with ... The primary outcome was frequency of steroid-free clinical remission at 1 year. Secondary outcomes included time to steroid-free clinical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11043477/

Ustekinumab in pediatric patients with Crohn's disease Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was ...

3. jnjmedicalconnect.com jnjmedicalconnect.com/products/stelara/medical-content/stelara-treatment-of-pediatric-crohns-disease

STELARA - Treatment of Pediatric Crohn's Disease Effectiveness. Steroid-free clinical remission was achieved by 79.73% (59/74) of patients at the 1-year follow-up.

4. nature.com nature.com/articles/s41598-025-09802-5

Long-term efficacy of therapeutic drug monitoring-guided ... In a systematic review of 38 studies of ustekinumab in patients with CD, 60% and 34% of patients achieved clinical response and remission with ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/jgh.16790

Long‐term clinical and endoscopic outcomes of ... Conclusions. Ustekinumab appeared effective in maintaining long-term clinical remission with endoscopic improvement in pediatric-onset Crohn's ...

6. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1371322/full

Ustekinumab in pediatric patients with Crohn's disease Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38665375/

Ustekinumab in pediatric patients with Crohn's disease Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was ...

8. innovativemedicine.jnj.com innovativemedicine.jnj.com/emea/newsroom/stelara-ustekinumab-receives-positive-chmp-opinion-for-the-treatment-of-moderately-to-severely-active-crohns-disease-in-paediatric-patients

STELARA® (ustekinumab) receives positive CHMP ... The proportion of paediatric patients weighing at least 40 kg who achieved clinical remission at induction Week 8 was 52.1% (25/48), with ...