Ustekinumab for Ulcerative Colitis

(UNIFI Jr Trial)

Recruiting at 81 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

112 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate: a) the efficacy of ustekinumab dosing in inducing clinical remission, b) safety profile of ustekinumab, and c) ustekinumab exposure (pharmacokinetics \[PK\]) in pediatric participants with moderately to severely active UC.

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.

What data supports the effectiveness of the drug ustekinumab for treating ulcerative colitis?

Research shows that ustekinumab can provide early symptom relief in patients with moderate-to-severe ulcerative colitis within the first 16 weeks of treatment. Additionally, it has been effective in maintaining improvement in patients with ulcerative colitis, as demonstrated in phase III trials. ^{1 2 3 4 5}

Is ustekinumab safe for humans?

Ustekinumab has been shown to be generally safe in clinical trials for ulcerative colitis, with low rates of adverse events (unwanted side effects) reported in studies lasting up to three years. ^{4 6 7 8 9}

How is the drug ustekinumab unique for treating ulcerative colitis?

Ustekinumab is unique because it targets specific proteins (interleukin-12 and interleukin-23) involved in inflammation, offering a different approach compared to other treatments that often target tumor necrosis factor (TNF). It is also administered as an intravenous induction followed by subcutaneous maintenance, which can be more convenient for some patients. ^{1 5 10 11 12}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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 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 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 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 (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]

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 (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]

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]

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

Early Symptomatic Improvement After Ustekinumab Therapy in Patients With Ulcerative Colitis: 16-Week Data From the UNIFI Trial. [2023]

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

Relationship Between Combined Histologic and Endoscopic Endpoints and Efficacy of Ustekinumab Treatment in Patients With Ulcerative Colitis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study. [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

One-year effectiveness and safety of ustekinumab in ulcerative colitis: a multicenter real-world study from Italy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Ustekinumab as induction and maintenance therapy for ulcerative colitis - national extended follow-up and a review of the literature. [2023]

8. England 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. [2020]

9. Korea (South) 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). [2021]

10. United States 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. [2021]

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

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

12. England pubmed.ncbi.nlm.nih.gov

A critical review of ustekinumab for the treatment of active ulcerative colitis in adults. [2023]