Open-label, Long-term Safety, Efficacy, and Pharmacokinetics Study of Vibegron in Pediatric Subjects 2 Years to < 18 Years of Age With NDO and on CIC

Official title

A Phase 2/3, Open-label, Baseline-controlled, Multicenter, Long-term Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Vibegron in Pediatric Subjects 2 Years to < 18 Years of Age With Neurogenic Detrusor Overactivity (NDO) on Clean Intermittent Catheterization (CIC)

Overview

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

Interventions

• Drug Vibegron
  Participants will be administered Vibegron orally, once daily (QD)

Primary outcome measures

• Change from Baseline in maximum cystometric capacity (MCC) based on bladder filling urodynamics [Time frame: Optimized Treatment Week 24]

Secondary outcome measures (12)

• Change from Baseline in MCC [Time frame: Optimized Week 12]
• Change from Baseline in number of overactive detrusor contractions until the end of bladder filling [Time frame: Optimized Treatment Weeks 12 and 24]
• Change from Baseline in detrusor pressure at the end of bladder filling [Time frame: Optimized Treatment Weeks 12 and 24]
• Change from Baseline in bladder filling volume until first involuntary/hyperactive detrusor contraction [Time frame: Optimized Treatment Weeks 12 and 24]
• Change from Baseline in bladder compliance (mL/cm H2O) [Time frame: Optimized Treatment Weeks 12 and 24]
• Change from Baseline in average first morning catheterized volume [Time frame: through study completion, an average of 52 weeks]
• Change from Baseline in average catheterized volume per catheterization [Time frame: through study completion, an average of 52 weeks]
• Change from Baseline in average maximum catheterized volume per day [Time frame: through study completion, an average of 52 weeks]
• Change from Baseline in average maximum catheterized daytime volume [Time frame: through study completion, an average of 52 weeks]
• Change from Baseline in average number of leakage episodes per day [Time frame: through study completion, an average of 52 weeks]
• Change from Baseline in estimated number of dry (leakage-free) days/ 7 days [Time frame: through study completion, an average of 52 weeks]
• Change from Baseline in Pediatric Incontinence Questionnaire (PIN-Q) [Time frame: through study completion, an average of 52 weeks]

Eligibility criteria

Inclusion criteria

• Male or female participants, age 2 years to < 18 years and weighing at least 11 kg at the Screening Visit.
• Participant has been diagnosed with NDO due to one of the following: spinal dysraphism, which includes spina bifida (eg, myelomeningocele, meningocele) and all forms of tethered cord; or acquired NDO from a spinal cord injury or spinal cord surgery, with the injury/surgery having occurred at least 6 months prior to the Screening Visit; or acquired NDO due to transverse myelitis with diagnosis at least 12 months prior to the Screening Visit.
• Participant undergoes CIC at least 3 times per 24 hours (with the last CIC performed prior to going to sleep for the night) for at least 4 weeks prior to the Screening Visit.

Exclusion criteria

• Participant has cerebral palsy, uncontrolled epilepsy, diabetes insipidus, or Stage 2 hypertension
• Participant has an active malignancy in the 12 months prior to the Screening Visit.
• Participant has been administered intravesical botulinum toxin within 9 months prior to the Screening Visit and should remain off this therapy during the study.
• Participant is taking digoxin or lithium within 10 days prior to Screening Visit or plans to start taking either during the study.
• Participant currently uses or plans to use a baclofen pump during the study.
• Participant has had urethral dilatation or urethral surgery in the 3 months prior to the Screening Visit.
• Participant has undergone bladder augmentation surgery.
• Participant has a known genitourinary condition (other than NDO) that may cause overactive contractions or incontinence (bladder exstrophy, urinary tract obstruction, urethral diverticulum or fistula) or bladder stones or another persistent urinary tract pathology that may cause symptoms.
• Participant has an insufficient urethral sphincter, has had implantation of an artificial sphincter, has a surgically-treated underactive urethral sphincter, or, in the 6 months prior to the Screening Visit, has undergone pelvic gender reassignment surgery.
• Participant has one of the following gastrointestinal problems: partial or complete obstruction, decreased motility such as paralytic ileus, risk of gastric retention, or malabsorption syndrome of any form.
• Participant has acute fecal impaction or, within the 3 months prior to the Screening Visit, had fecal impaction that required hospitalization or ambulatory surgical treatment.
• Participant had a urinary indwelling catheter in the 4 weeks prior to the Screening Visit.
• Participant has moderate to severe dilating vesicoureteral reflux (Grade IV to V) or severe renal failure.
• Participant started electrostimulation/neuromodulation therapy in the 4 weeks before the Screening Visit, or is expected to start this therapy during the study period.
• Participant has participated in another clinical trial and/or has taken an investigational drug within 4 weeks prior to the Screening Visit.
• Participant is unable, or parent/caregiver is not willing, to washout any medication for the management of NDO.
• Participant is a female of childbearing potential who is unwilling or unable to use a highly effective method of contraception for the duration of the study.
• Female participants who are currently breastfeeding or plan to breastfeed any time from the Screening Visit until 28 days after the final study drug administration.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 11 centers

• Arkansas Childrens Hospital — Little Rock
• Children's Hospital of Orange County — Orange
• Children's Hospital Colorado — Aurora
• Nemours Childrens Health, Jacksonville — Jacksonville
• Wichita Urology Group — Wichita
• Childrens Hospital New Orleans — New Orleans
• Albany Medical College — Albany
• SUNY Upstate Medical University — Syracuse
• … and 3 more centers

Jordan · 3 centers

• Istiklal Hospital — Amman
• Jordan University Hospital — Amman
• Irbid Specialty Hospital — Irbid

Poland · 3 centers

• Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa — Bialystok
• Uniwersyteckie Centrum Kliniczne — Gdansk
• Instytut Pomnik - Centrum Zdrowia Dziecka — Warsaw

Belgium · 2 centers

• Universitair Ziekenhuis Antwerpen — Edegem
• UZ Gent — Ghent

Canada · 2 centers

• Alberta Children's Hospital — Calgary
• The Hospital for Sick Children — Toronto

Lithuania · 2 centers

• Hospital of Lithuanian University of Health Sciences Kauno klinikos — Kaunas
• Vilnius University Hospital Santaros Klinikos — Vilnius

Malaysia · 2 centers

• Kuala Lumpur Hospital — Kuala Lumpur
• Hospital Umum Sarawak — Kuching

Romania · 2 centers

• Institutul Clinic Fundeni — Bucharest
• Maria Sklodowska Curie Childrens Clinical Emergency Hospital — Bucharest

Serbia · 2 centers

• University Children's Hospital Tirsova — Belgrade
• Children and Youth Health Care Institute of Vojvodina — Novi Sad

Slovakia · 2 centers

• Detská fakultná nemocnica s poliklinikou/Národný ústav detských chorôb (NÚDCH) — Bratislava
• Urologická ambulancia J. BREZA MEDICAL s.r.o. — Bratislava

Turkey (Türkiye) · 2 centers

• Ankara University Faculty of Medicine Ibni Sina Hospital — Ankara
• Mersin University, Dept. of Urology — Yenişehir

Croatia · 1 center

• University Hospital Split - KBC Split — Split

Denmark · 1 center

• Aarhus University Hospital - Department of Paediatrics and Adolescent Medicine — Aarhus

Georgia · 1 center

• JSC Evex Hospital M. lashvili Childrens Central Hospital — Tbilisi

Latvia · 1 center

• Childrens Clinical University Hospital — Riga

Philippines · 1 center

• National Children's Hospital — Quezon City

Identifiers

NCT: NCT05491525 · URO-901-3007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗