Evaluation of Vibegron for Safety, Efficacy, and Pharmacokinetics in Pediatric Patients with Neurogenic Detrusor Overactivity on Clean Intermittent Catheterization

The primary objective of this study is to evaluate the **efficacy** of once-daily (QD) administration of vibegron in pediatric subjects aged 2 years to less than 18 years with **Neurogenic Detrusor Overactivity (NDO)**. This is clinically relevant as NDO can significantly impact the quality of life in pediatric patients, and effective management is crucial for improving bladder function and reducing associated complications.

Secondary objectives include:

• To evaluate the safety and tolerability of vibegron in the same pediatric population, which is essential for ensuring that the treatment is not only effective but also safe for long-term use.
• To assess the pharmacokinetic (PK) profile of vibegron after multiple-dose administration, providing insights into the drug's absorption, distribution, metabolism, and excretion in pediatric subjects with NDO.

The clinical trial involves a total of **53 participants** diagnosed with **Neurogenic Detrusor Overactivity (NDO)**. The study population comprises both male and female subjects aged between 2 years and less than 18 years. Participants are divided into two cohorts based on age and weight: Cohort 1 includes those aged 12 to less than 18 years who must weigh at least 29.5 kilograms, while Cohort 2 includes those aged 2 to less than 12 years who must weigh at least 11 kilograms. The trial population was selected based on specific inclusion criteria, including a diagnosis of NDO due to conditions such as spinal dysraphism, acquired NDO from spinal cord injury or surgery, or transverse myelitis. Participants are required to perform clean intermittent catheterization (CIC) at least three times per 24 hours for a minimum of four weeks prior to the screening visit. The study includes a vulnerable population, and lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of **vibegron** in pediatric subjects aged 2 to less than 18 years with **neurogenic detrusor overactivity** (NDO) who are on clean intermittent catheterization (CIC). This is a Phase II/III, open-label, baseline-controlled, multicenter study. The trial will involve the administration of vibegron orally, in the form of granules or film-coated tablets, with a maximum treatment period of 52 weeks. The study is expected to commence recruitment on February 12, 2024, and conclude by March 31, 2029.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, weight, and diagnosis of NDO. The trial will include multiple follow-up visits to assess primary and secondary endpoints, including changes in maximum cystometric capacity (MCC) and other urodynamic parameters, as well as safety assessments through adverse event monitoring, vital signs, and laboratory tests. The primary endpoint will be evaluated at Study Week 32, while secondary endpoints will be assessed at various intervals, including Study Weeks 1, 4, 8, 20, 32, 48, and 52.

The expected duration of participant involvement is up to 52 weeks, with conditions for early termination including the occurrence of adverse events or withdrawal of consent. The study will also assess the pharmacokinetics of vibegron, measuring parameters such as Cmax, tmax, and AUC(0-24h). The trial's design ensures a comprehensive evaluation of vibegron's long-term safety and efficacy in the pediatric population with NDO.

The clinical trial involves the administration of **Vibegron**, a pharmaceutical product developed by Urovant Sciences GmbH. Vibegron is provided in two pharmaceutical forms: **granules** and **film-coated tablets**. The active substance in both forms is vibegron, which is of chemical origin. The granules are administered orally with a maximum daily dose of 5 mg, 10 mg, 20 mg, 50 mg, or 75 mg, depending on the specific formulation used in the trial. The maximum total dose for the granules ranges from 1,820 mg to 27,300 mg over a treatment period of up to 52 weeks. The film-coated tablets are also administered orally, with a maximum daily dose of 50 mg or 75 mg, and a maximum total dose of 18,200 mg to 27,300 mg over the same treatment period.

In this study, Vibegron is the experimental medication, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The administration of Vibegron is conducted under controlled conditions to ensure participant compliance, with dosing schedules tailored to the specific needs of pediatric subjects aged 2 to less than 18 years with neurogenic detrusor overactivity (NDO) on clean intermittent catheterization (CIC). The trial aims to evaluate the safety, efficacy, and pharmacokinetics of Vibegron in this population. Monitoring of participant compliance is integral to the study, ensuring adherence to the prescribed dosing regimen and accurate assessment of the drug's effects.

The efficacy of **vibegron** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline at Study Week 32 in Maximum Cystometric Capacity (MCC) based on filling urodynamics. Secondary efficacy endpoints will be evaluated through various measures, including changes from baseline in MCC at Study Week 20, as well as changes in the number of overactive detrusor contractions, detrusor pressure at the end of filling, filling volume until the first involuntary detrusor contraction, and bladder compliance at Study Weeks 20 and 32.

Additional secondary endpoints will be assessed using bladder diaries, with changes from baseline measured at Study Weeks 1, 4, 8, 20, 32, 48, and 52. These include average first morning catheterized volume, average catheterized volume per catheterization, average maximum catheterized volume per day, average maximum catheterized daytime volume, average number of leakage episodes per day, and estimated number of dry days per week. Questionnaires will also be utilized to assess changes from baseline in the Pediatric Incontinence Questionnaire (PIN-Q) and Patient Global Impression of Severity (PGI-S) Scale at Study Weeks 20, 32, and 52, along with the Clinical Global Impression of Change (CGI-C) Scale at the same timepoints.

The trial will employ validated scales and tools for these assessments, ensuring the reliability and accuracy of the data collected. The schedule for measuring and collecting these efficacy parameters is structured to provide comprehensive insights into the treatment's impact over time, with specific timepoints designated for each type of assessment. This structured approach will facilitate a thorough analysis of the efficacy of vibegron in pediatric subjects with neurogenic detrusor overactivity.