Ustekinumab for Ulcerative Colitis

(UNIFI Jr Trial)

No longer recruiting at 98 trial locations

Overseen By Study Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Rectal UC, Obstruction, Infections, Malignancy, 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 the effectiveness of ustekinumab (Stelara) for children with moderate to severe ulcerative colitis (UC), a condition causing inflammation in the colon and symptoms like frequent diarrhea and abdominal pain. Researchers aim to determine if ustekinumab can induce clinical remission (a reduction or disappearance of symptoms) and ensure its safety for children. The study includes different groups: one group receives an initial intravenous dose, followed by doses every 8 or 12 weeks. The trial seeks children diagnosed with UC whose symptoms significantly disrupt daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering early access to a potentially effective treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that ustekinumab, also known as STELARA®, is generally safe. In studies involving over 2,500 patients, it was monitored for a total of 4,826 patient-years, indicating long-term observation. The results showed that ustekinumab was usually well-tolerated, with most side effects being mild or moderate.

The most common side effects included headaches, fatigue, and upper respiratory infections, similar to a cold. Serious side effects were rare. These studies suggest that ustekinumab is safe for individuals with inflammatory bowel diseases, such as ulcerative colitis. However, discussing any concerns with a doctor before joining a trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Researchers are excited about ustekinumab for ulcerative colitis because it offers a unique approach to treatment by targeting interleukin-12 and interleukin-23, proteins involved in inflammatory processes. Unlike traditional therapies like corticosteroids or mesalamine, which broadly suppress the immune response, ustekinumab specifically blocks these proteins, potentially reducing inflammation more precisely and with fewer side effects. Additionally, its dosing schedule is convenient, with an initial IV administration followed by infrequent maintenance doses every 8 or 12 weeks, which could improve adherence and quality of life for patients. This targeted mechanism and patient-friendly dosing set ustekinumab apart from current treatment options.

What evidence suggests that ustekinumab might be an effective treatment for ulcerative colitis?

Studies have shown that ustekinumab effectively treats ulcerative colitis (UC), even in patients unresponsive to other treatments. In one study, 42% to 54% of patients were symptom-free after 56 weeks of ustekinumab treatment. Another long-term study found that about 70% of patients remained symptom-free after 200 weeks. Real-world data supports these findings, demonstrating that ustekinumab works well and is safe for many UC patients. Overall, the evidence suggests that ustekinumab can help reduce symptoms and maintain symptom-free status in people with UC. Participants in this trial will receive ustekinumab during both the induction and maintenance periods, with different dosing schedules tested to determine the most effective regimen. ^{6 7 8 9 10}

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 moderate to severe Ulcerative Colitis (UC). They must have a confirmed diagnosis of UC, a Mayo score of 6-12, and an endoscopy subscore >=2. Girls who can have babies need a negative pregnancy test. Kids can't join if they only have rectal UC, recent bowel blockages, certain infections like TB or fungal diseases, any cancer history, or allergies to ustekinumab.

Inclusion Criteria

Medically stable on the basis of physical examination, medical history, and vital signs, performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and acknowledged by the investigator

My ulcerative colitis is moderate to severe, with a Mayo score of 6-12.

I was diagnosed with ulcerative colitis before screening.

Exclusion Criteria

I have had infections like histoplasmosis or similar conditions before.

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

My ulcerative colitis affects only my rectum or less than 20 cm of my colon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive a single intravenous administration of ustekinumab at induction Week 0 based on body surface area or weight-tiered induction dose

8 weeks

1 visit (in-person)

Maintenance

Participants receive subcutaneous administration of ustekinumab every 8 or 12 weeks based on body surface area or weight-tiered induction dose

44 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

22 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ustekinumab

Trial Overview The study tests Ustekinumab's effectiveness in causing remission in kids with UC and checks its safety and how the body processes it. Participants will either receive Ustekinumab doses based on their size or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Maintenance (M) Period: Ustekinumab once every 8 Week (q8w) Experimental Treatment 2 Interventions

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

Group II: Maintenance (M) Period: Ustekinumab once every 12 Week (q12w) Experimental Treatment 2 Interventions

Participants will receive SC administration of ustekinumab every 12 weeks (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: Induction Period (I): Ustekinumab Experimental Treatment 1 Intervention

All participants will receive a single intravenous (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

Ustekinumab (STELARA) is effective for treating moderate-to-severe plaque psoriasis in pediatric patients aged 6 to 12, as shown by a phase III study that developed a pharmacokinetic model to predict its behavior in this age group.

The study successfully used data from adult patients to create a model that predicts clinical responses in children, indicating that ustekinumab's efficacy and safety profile can be extrapolated from adults to younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. Zhou, W., Hu, C., Zhu, Y., et al.[2021]

Ustekinumab (UST) demonstrated efficacy in inducing and maintaining clinical remission in East-Asian patients with moderate to severe ulcerative colitis, with 11.4% and 11.1% of patients achieving remission at week 8 compared to 0% in the placebo group.

The safety profile of UST was generally favorable, with only a few serious adverse events reported and no deaths during the study, indicating that UST is a safe treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ustekinumab in East Asian patients with moderately to severely active ulcerative colitis: a subpopulation analysis of global phase 3 induction and maintenance studies (UNIFI). Hisamatsu, T., Kim, HJ., Motoya, S., et al.[2021]

In a study of 14 patients with moderate-to-severe ulcerative colitis, ustekinumab demonstrated sustained efficacy beyond 3 years, with 85.7% of patients continuing treatment and a clinical relapse rate of 42.9%.

The safety profile remained favorable, with only three serious adverse events reported and no new safety signals identified during a median follow-up of 5.7 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab as induction and maintenance therapy for ulcerative colitis - national extended follow-up and a review of the literature. Chetwood, JD., Gupta, S., Subramaniam, K., et al.[2023]

In a study of 103 patients with moderate-to-severe ulcerative colitis, ustekinumab achieved steroid-free clinical remission in 35% of patients within 12-16 weeks, indicating its effectiveness in a real-world setting, especially among those with multiple prior treatment failures.

The study found that higher disease severity at the start and a history of treatment with both anti-TNF agents and vedolizumab were linked to lower rates of remission, while adverse events were relatively low at 7.8%, suggesting ustekinumab is a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real-world cohort study. Amiot, A., Filippi, J., Abitbol, V., et al.[2020]

Ustekinumab is an effective treatment for moderate-to-severe ulcerative colitis, demonstrating the ability to induce and maintain clinical, endoscopic, and histologic remission in both phase 3 trials and real-world studies.

The drug has a favorable safety profile and is considered a strong option for first, second, or third-line therapy, especially for patients who have not responded to other biologics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical review of ustekinumab for the treatment of active ulcerative colitis in adults. Vieujean, S., Louis, E., Danese, S., et al.[2023]

In a real-world study of 103 patients with ulcerative colitis treated with ustekinumab, 32% achieved steroid-free clinical remission after 52 weeks, indicating its effectiveness in managing refractory cases.

However, 44% of patients discontinued treatment mainly due to lack of effectiveness, and there were adverse effects in 16.9% of patients, including severe cases, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study. Fumery, M., Filippi, J., Abitbol, V., et al.[2021]

Ustekinumab (STELARA) is a safe and effective treatment for skin conditions related to inflammatory bowel diseases (IBD), including metastatic Crohn's disease and pyoderma gangrenosum, based on a review of 22 articles.

It also effectively addresses paradoxical skin reactions caused by TNF-α inhibitors, such as psoriasis, particularly when these reactions do not improve with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases. Wu, J., Smogorzewski, J.[2021]

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]

Citations

1. stelarahcp.com stelarahcp.com/ulcerative-colitis/efficacy

Ulcerative Colitis (UC): Efficacy - Stelara Find STELARA® (ustekinumab) efficacy data, including clinical response and study design information. See full Prescribing & Safety Information.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38531068/

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis ... Ustekinumab was shown to be efficacious and safe in a population of patients with refractory ulcerative colitis.

3. gi.org gi.org/journals-publications/ebgi/dalal_jul2024/

Long-Term Efficacy and Safety of Ustekinumab for ... Of 171 patients who completed endoscopic evaluations at week 200, approximately 70% in both groups had clinical remission and approximately 80% ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10565585/

Real-world effectiveness of ustekinumab for patients with ... The effectiveness of ustekinumab in real-world patients with UC was consistent with the results clinical trials. Moreover, previous treatment with anti-TNF ...

5. academic.oup.com academic.oup.com/crohnscolitis360/article/6/2/otae024/7645311

Effectiveness and Persistency of Ustekinumab Treatment for ... In UC with bio-failure, at 56 weeks following UST induction, the remission and response rates were 42%–54% and 65%–75% in this cohort; ...

6. stelarahcp.com stelarahcp.com/ulcerative-colitis/safety

Ulcerative Colitis (UC): Safety Profile - Stelara The safety of STELARA® was evaluated in 2 randomized, double-blind, placebo-controlled clinical studies in 960 adult patients with moderately to severely ...

7. jnj.com jnj.com/media-center/press-releases/new-stelara-ustekinumab-long-term-data-support-its-established-safety-profile-in-inflammatory-bowel-disease-and-durable-efficacy-in-ulcerative-colitis

New STELARA® (ustekinumab) Long-Term Data Support ... A final pooled safety analysis of six Phase 2/3 IBD studies included 2,575 patients treated with STELARA and a total of 4,826 patient-years (PY) ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38310565/

Safety of Ustekinumab in Inflammatory Bowel Disease The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo.

9. academic.oup.com academic.oup.com/ecco-jcc/article/18/7/1091/7600484

Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled ... The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo and continue to support ...

10. ema.europa.eu ema.europa.eu/en/documents/product-information/stelara-epar-product-information_en.pdf

Stelara, INN-ustekinumab - EMA The safety and efficacy of STELARA for the treatment of Crohn's disease in paediatric patients weighing less than 40 kg or ulcerative colitis in children less ...