Vibegron for Pediatric Bladder Disorder

(KANGUROO Trial)

Recruiting at 5 trial locations

Overseen By Study Director

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Urovant Sciences GmbH

Must not be taking: Digoxin, Lithium, others

Disqualifiers: Cerebral palsy, Uncontrolled epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

85 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, efficacy, and PK of vibegron in pediatric participants with NDO who are regularly using CIC

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as digoxin, lithium, and intravesical botulinum toxin, before joining. If you are taking medications for NDO, you must be willing to stop them for the study.

What data supports the effectiveness of the drug Vibegron for pediatric bladder disorder?

Research shows that Vibegron is effective in treating overactive bladder in adults and has shown high efficacy in pediatric patients with daytime urinary incontinence, which suggests it may help with pediatric bladder disorders. ^{1 2 3 4 5}

How is the drug vibegron unique for treating pediatric bladder disorders?

Vibegron is unique because it is a selective beta 3 adrenergic receptor agonist, which means it works by relaxing the bladder muscle to help reduce symptoms of overactive bladder. This mechanism is different from other treatments that may not target this specific receptor, making it a novel option for pediatric patients with bladder disorders. ^{1 4 6 7 8}

Eligibility Criteria

This trial is for children aged 2 to <18 with Neurogenic Detrusor Overactivity (NDO) due to spinal conditions or injury, who use Clean Intermittent Catheterization (CIC). They must weigh at least 11 kg if under 12 years old, and at least 29.5 kg if between 12 and <18 years old. Those with recent urethral procedures, bladder surgeries, active cancers, certain medication usage or unwillingness to stop NDO medications are excluded.

Inclusion Criteria

I am aged 2 to under 12 years and weigh at least 11 kg.

I am aged 12-17 and weigh at least 29.5 kg.

I am between 2 and 17 years old.

Exclusion Criteria

I am not breastfeeding nor plan to during the study and until 28 days after the last drug dose.

I have cerebral palsy, uncontrolled epilepsy, diabetes insipidus, or high blood pressure.

I have a serious digestive issue, like blockage or poor movement in my intestines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive vibegron based on their weight, with dose adjustments based on clinical condition, PK, and safety/tolerability data

20 weeks

Regular visits for dose adjustments and monitoring

Treatment Part B

Participants receive a DSMB-selected vibegron dose for their weight determined from Part A data

32 weeks

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vibegron

Trial Overview The study tests the safety and effectiveness of a drug called Vibegron in young patients with overactive bladders due to NDO. It will also assess how the body processes the drug. Participants are divided into two groups based on age: one for ages 2-<12 and another for ages 12-<18.

Participant Groups

Group I: Cohort 2: Vibegron Children (2 to < 12 years) Experimental Treatment 1 Intervention

Part A: Participants aged 2 to \< 12 years will receive vibegron based on their weight, after DSMB review of Cohort 1, Part A data, with dose reduction based on individual clinical condition, PK, and safety/tolerability data. Participants may be dose-reduced up to 2 times. Part B: Participants will receive a DSMB-selected vibegron dose for their weight determined from participants in their respective cohort and weight band of Part A.

Group II: Cohort 1: Vibegron Adolescents (12 to < 18 years) Experimental Treatment 1 Intervention

Part A: Participants aged 12 to \< 18 years will receive vibegron based on their weight, with dose reduction based on individual clinical condition, PK, and safety/tolerability data. Participants may be dose-reduced up to 2 times. Part B: Participants will receive a Data and Safety Monitoring Board (DSMB)-selected vibegron dose for their weight determined from participants in their respective cohort and weight band of Part A.

Vibegron is already approved in United States, Japan for the following indications:

Approved in United States as Gemtesa for:

• Overactive bladder symptoms of urge urinary incontinence, urgency, and urinary frequency in adults
• Men taking medicines for benign prostatic hyperplasia (BPH)

Approved in Japan as Vibegron for:

• Overactive bladder symptoms of urge urinary incontinence, urgency, and urinary frequency

Who Is Running the Clinical Trial?

Urovant Sciences GmbH

Lead Sponsor

Trials

11

Recruited

4,300+

Findings from Research

In a study of 15 patients with spina bifida and antimuscarinic-resistant neurogenic bladder dysfunction, vibegron significantly improved bladder compliance and maximum cystometric bladder capacity compared to previous antimuscarinic treatments.

No new adverse events were reported during vibegron treatment, indicating it is a safe and well-tolerated option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Video-urodynamic effects of vibegron, a new selective β3-adrenoceptor agonist, on antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida. Aoki, K., Momose, H., Gotoh, D., et al.[2022]

In a study involving 188 patients with overactive bladder (OAB), vibegron demonstrated significant improvement in OAB symptoms after 8 weeks of treatment, indicating its efficacy as a first-line therapy and for patients switching from other medications.

Vibegron was well-tolerated, with an overall adverse event rate of 25%, and no severe adverse events (grade 3 or higher) reported, highlighting its safety in real-world clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vibegron in patients with overactive bladder: Multicenter prospective study of real-world clinical practice in Japan, SCCOP study 19-01. Tachikawa, K., Kyoda, Y., Fukuta, F., et al.[2022]

In a study involving Korean patients with overactive bladder (OAB), a daily dose of 50 mg vibegron significantly improved symptoms such as daily micturition and urgency incontinence compared to placebo over 12 weeks.

Vibegron was found to be safe and well-tolerated, with a similar incidence of adverse events compared to the placebo group, and no serious side effects or significant changes in heart function were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder. Shin, JH., Jeong, SJ., Kim, SO., et al.[2023]

In a study of 57 pediatric patients treated with vibegron for daytime urinary incontinence (DUI), the overall response rate after 6 months was 68.3%, indicating that vibegron is an effective treatment option for this condition.

Patients with neurodevelopmental disorders (NDDs) showed a slightly higher response rate of 72.0%, and those treated with vibegron as a first choice had the best response rate of 85.0%, suggesting that vibegron can be particularly beneficial for children with DUI, including those with complex needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vibegron shows high efficacy in pediatric patients with refractory daytime urinary incontinence. Hyuga, T., Tanabe, K., Kubo, T., et al.[2023]

In a study comparing 180 patients on mirabegron and 132 on vibegron for overactive bladder, vibegron had a significantly higher 1-year continuation rate of 83.8% compared to 58.2% for mirabegron, indicating better long-term adherence.

Discontinuation due to inadequate efficacy was much lower for vibegron (8.7%) than for mirabegron (29.1%), suggesting that vibegron may provide more effective symptom control for patients with overactive bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 1-year continuation rate and discontinuation factors of vibegron and mirabegron: A retrospective comparative study in a rehabilitation hospital in Japan. Mukai, S., Nomi, M., Yamada, S., et al.[2021]

Vibegron is a selective beta 3 adrenergic receptor agonist developed for treating overactive bladder (OAB), and it received approval in Japan in September 2018 based on positive results from phase III trials.

The development of vibegron marks a significant milestone in OAB treatment, as it is being introduced globally by Urovant Sciences, expanding treatment options for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vibegron: First Global Approval. Keam, SJ.[2019]

Vibegron, a β3-adrenoceptor agonist, was found to be equally effective in treating overactive bladder symptoms in patients aged 65 and older compared to those younger than 65, based on a 12-week study with randomized, placebo-controlled design.

The treatment did not significantly affect cardiovascular parameters such as blood pressure and pulse rate, indicating that vibegron is safe for use in older adults with minimal cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of vibegron, a new β3-adrenoceptor agonist, in older patients with overactive bladder: Post-hoc analysis of a randomized, placebo-controlled, double-blind comparative phase 3 study. Yoshida, M., Takeda, M., Gotoh, M., et al.[2022]

Vibegron, a β3-adrenergic receptor agonist, significantly reduced symptoms of overactive bladder (OAB) in a pooled analysis of three high-quality randomized controlled trials involving 2120 patients, showing improvements in micturition and urgency episodes.

The treatment was well-tolerated with a favorable safety profile, indicating that Vibegron is a promising option for managing OAB symptoms without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of Vibegron in treating overactive bladder: A systematic review and pooled analysis of randomized controlled trials. Shi, H., Chen, H., Zhang, Y., et al.[2020]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Video-urodynamic effects of vibegron, a new selective β3-adrenoceptor agonist, on antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of vibegron in patients with overactive bladder: Multicenter prospective study of real-world clinical practice in Japan, SCCOP study 19-01. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder. [2023]

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

Vibegron shows high efficacy in pediatric patients with refractory daytime urinary incontinence. [2023]

5. Australia pubmed.ncbi.nlm.nih.gov

The 1-year continuation rate and discontinuation factors of vibegron and mirabegron: A retrospective comparative study in a rehabilitation hospital in Japan. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Vibegron: First Global Approval. [2019]

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

Cardiovascular safety of vibegron, a new β3-adrenoceptor agonist, in older patients with overactive bladder: Post-hoc analysis of a randomized, placebo-controlled, double-blind comparative phase 3 study. [2022]

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

The efficacy and safety of Vibegron in treating overactive bladder: A systematic review and pooled analysis of randomized controlled trials. [2020]