Long-Term Ustekinumab for Pediatric Crohn's Disease

(UNITED Trial)

Recruiting in Palo Alto (17 mi)

+57 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Must be taking: Ustekinumab

Disqualifiers: Pregnancy, COVID-19, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to collect long-term safety data of subcutaneous (SC) ustekinumab

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.

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

Ustekinumab has shown effectiveness in achieving clinical remission in about 50% of adult Crohn's disease patients after one year, and a case study reported a 10-year-old girl with Crohn's disease achieving remission without adverse effects over 75 weeks. This suggests ustekinumab may be a promising option for pediatric patients as well. ^{1 2 3 4 5}

Is ustekinumab safe for children with Crohn's disease?

In a case study of a 10-year-old girl with Crohn's disease, ustekinumab was used without any adverse events like infusion reactions or increased risk of infection over 75 weeks, suggesting it may be a safe treatment option for pediatric patients. ^{4 6 7 8 9}

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

Ustekinumab is unique because it targets specific proteins (interleukin-12 and interleukin-23) involved in inflammation, unlike other treatments that target tumor necrosis factor (TNF). It is used when other treatments like immunomodulators or TNF antagonists have failed, and it can be administered both intravenously and subcutaneously. ^{1 3 5 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Ustekinumab (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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]

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 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]

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

Ustekinumab in Pediatric Crohn Disease Patients. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry. [2023]

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

Real-World Effectiveness and Safety of Ustekinumab in Elderly Crohn's Disease Patients. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Real World Experience With Ustekinumab in Children and Young Adults at a Tertiary Care Pediatric Inflammatory Bowel Disease Center. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience. [2019]