Ustekinumab for Pediatric Crohn's Disease

(UNITI Jr Trial)

No longer recruiting at 85 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called ustekinumab to determine its effectiveness for children with Crohn's disease, a condition that inflames the digestive tract. Researchers aim to assess how well ustekinumab induces and maintains remission, reducing symptoms and flare-ups, and to evaluate its safety for children. The trial includes different treatment groups: one group receives ustekinumab through an IV once, while others receive injections every 8 or 12 weeks. Children with moderate to severe Crohn's disease, confirmed by a doctor, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for Crohn's disease in children.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ustekinumab is generally well-tolerated by children with Crohn's disease. Studies have found that ustekinumab helps many children achieve significant improvement in their symptoms, known as clinical remission. While the treatment has proven effective, awareness of possible side effects is important. Common side effects include headache, tiredness, and nausea, though not everyone experiences these.

Regarding safety, previous data suggest that ustekinumab usually does not cause serious side effects in most patients. However, as each person's body can react differently, staying informed and discussing any concerns with a healthcare provider is crucial. This treatment is in advanced testing, and its safety is well-understood, but ongoing studies continue to monitor its effects to ensure safety for all participants. ^{1 2 3 4 5}

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

Researchers are excited about ustekinumab for pediatric Crohn's disease because it offers a different approach compared to traditional treatments like corticosteroids and immunosuppressants. Unlike these options, which broadly suppress the immune system, ustekinumab targets specific proteins (IL-12 and IL-23) that play key roles in inflammation. This targeted action could potentially reduce side effects while effectively managing symptoms. Additionally, its flexible dosing options, including both intravenous and subcutaneous methods, offer convenience and adaptability for young patients.

What evidence suggests that ustekinumab might be an effective treatment for pediatric Crohn's disease?

Research has shown that ustekinumab effectively treats Crohn's disease in children. Studies found that 79.73% of children taking ustekinumab achieved steroid-free remission after one year, no longer needing steroids to control symptoms. The treatment has a good safety record for children. Overall, evidence supports that ustekinumab can help children with Crohn's disease feel better and manage symptoms more effectively. Participants in this trial will receive ustekinumab either intravenously during the induction period or subcutaneously during the maintenance period. ^{1 6 7 8 9}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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 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 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]

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 The primary outcomes were clinical remission at weeks 24–32 and weeks 48–56 of UST therapy. Secondary outcomes were clinical response at the ...

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. naspghan.org naspghan.org/wp-content/uploads/2019/10/July-2019-Article-A.pdf

Real World Experience With Ustekinumab in Children and ... Conclusions: Our results suggest that ustekinumab is efficacious and safe in pediatric patients with IBD. Controlled clinical trial data are ...

5. 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 ... STELARA® (ustekinumab) receives positive CHMP opinion for the treatment of moderately to severely active Crohn's disease in paediatric patients.

6. 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 ...

7. stelarahcp.com stelarahcp.com/crohns-disease/safety-profile

Crohn's Disease (CD): Safety Profile View STELARA® (ustekinumab) safety profile data, including common adverse reactions and additional safety information. See full Prescribing & Safety ...

8. fda.gov fda.gov/media/187210/download?attachment

Pediatric Postmarketing Pharmacovigilance Review The safety and effectiveness of STELARA® have not been established in pediatric patients with Crohn's disease or ulcerative colitis. 2 METHODS ...

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

Ustekinumab in pediatric patients with Crohn's disease Conclusions: UST is efficacious and safe in pediatric patients with CD. Pediatric patients could benefit from UST as either a primary or ...