Efficacy, Safety, and Pharmacokinetics of Ustekinumab in Pediatric Patients with Moderate to Severe Ulcerative Colitis: A Phase 3 Randomized Controlled Trial

The primary objective of this Phase 3 study is to evaluate the **efficacy** of ustekinumab dosing in inducing clinical remission in pediatric participants with moderately to severely active **ulcerative colitis**. This is clinically relevant as achieving remission can significantly improve the quality of life and reduce the long-term complications associated with this chronic inflammatory condition. Additionally, the study aims to assess the **safety profile** of ustekinumab in this population, which is crucial for understanding the risk-benefit ratio of the treatment. Another primary objective is to evaluate ustekinumab **exposure** (pharmacokinetics) to ensure appropriate dosing and therapeutic levels are achieved in pediatric patients.

The clinical trial involves a total of **59 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population comprises pediatric subjects, including both male and female participants, indicating a diverse gender representation. Participants are medically stable, as determined by physical examination, medical history, and vital signs, with any abnormalities being consistent with the underlying illness. The trial includes individuals with a baseline Mayo score ranging from 6 to 12, and a screening Mayo endoscopy subscore of 2 or higher. The selection process ensures that participants have been diagnosed with ulcerative colitis prior to screening. The trial also considers lifestyle factors such as the requirement for females of childbearing potential to have a negative highly sensitive urine pregnancy test at screening and prior to study intervention administration. The study population includes vulnerable groups, reflecting the careful consideration of ethical standards in the selection process.

The clinical trial is designed to evaluate the **efficacy**, safety, and pharmacokinetics of **ustekinumab** in pediatric participants with moderately to severely active **ulcerative colitis**. This is a Phase 3 study involving an open-label intravenous induction treatment followed by a randomized, double-blind, subcutaneous maintenance phase. The trial is expected to last until June 2025, with recruitment having commenced in January 2021. Participants will be involved in the study for a maximum treatment period of 40 weeks.

The trial includes several key study visits. Initially, a screening visit will be conducted to confirm eligibility based on inclusion criteria, such as a diagnosis of ulcerative colitis and a baseline Mayo score of 6 through 12. Participants must also have a negative pregnancy test if applicable. Following the screening, eligible participants will undergo an induction phase with intravenous ustekinumab, followed by randomization into the maintenance phase where they will receive either subcutaneous ustekinumab or placebo. The primary endpoint is clinical remission at Week 8.

Follow-up visits will be scheduled to monitor the participants' response to the treatment and assess any adverse events. The end-of-study visit will conclude the trial, where final assessments will be made. Participants may be withdrawn from the study early if they experience significant adverse effects or if they do not adhere to the study protocol. The trial aims to provide comprehensive data on the use of ustekinumab in this patient population, contributing to the understanding of its therapeutic potential in managing ulcerative colitis.

The clinical trial involves the administration of **STELARA** in various formulations to evaluate its efficacy, safety, and pharmacokinetics in pediatric participants with moderately to severely active **ulcerative colitis**. The experimental medication, **STELARA 90 mg**, is provided as a solution for injection in a pre-filled syringe. The active substance is **ustekinumab**, a protein-based therapeutic agent. The medication is administered via **subcutaneous use**. The maximum daily dose is 90 mg, with a total dose not exceeding 450 mg over a treatment period of up to 40 weeks. The administration is facilitated by the UltraSafe Passive Delivery System, a needle guard system that complies with ISO standards, ensuring safe and effective delivery.

Another formulation, **STELARA 130 mg**, is a concentrate for solution for infusion, also containing **ustekinumab**. This formulation is administered through **intravenous use**. The maximum dose for this formulation is 520 mg, administered as a single infusion. This formulation is intended for the induction phase of the treatment, providing a rapid onset of action.

Additionally, the trial includes the use of **STELARA 45 mg**, a solution for injection, which is also administered subcutaneously. This formulation contains the same active substance, **ustekinumab**, and is used in a similar dosing regimen as the 90 mg formulation, with a maximum daily dose of 60 mg and a total dose not exceeding 300 mg over a 40-week period.

To maintain the integrity of the study, two placebo groups are included, referred to as **Placebo 1** and **Placebo 2**. These placebos do not contain any active substance and are used to ensure the double-blind nature of the trial. The placebo administration mimics the experimental treatments in terms of appearance and administration route, ensuring that participants and investigators remain blinded to the treatment assignments.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to provide comprehensive data on the therapeutic potential of **ustekinumab** in the target population, contributing to the understanding of its role in managing **ulcerative colitis**.

The efficacy of **ustekinumab** in the clinical trial will be assessed by evaluating its ability to induce clinical remission in pediatric participants with moderately to severely active **ulcerative colitis**. The primary endpoint for efficacy is clinical remission at Week I-8. This endpoint will be measured using the Mayo score, which is a validated scale for assessing disease activity in ulcerative colitis. Participants must have a baseline Mayo score of 6 through 12, inclusive, with a screening Mayo endoscopy subscore of at least 2, as determined by a central review of the endoscopy video.

The trial involves an open-label intravenous induction treatment followed by a randomized double-blind subcutaneous maintenance phase. The efficacy assessments will be conducted at specified timepoints, including the critical assessment at Week I-8. The trial is designed to ensure that the efficacy of ustekinumab is thoroughly evaluated in terms of its ability to achieve clinical remission in the target population. The data collected will be analyzed to determine the effectiveness of ustekinumab in managing the symptoms of ulcerative colitis in pediatric patients.