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 (KANGUROO)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sumitomo Pharma America Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

28 Jul 2023 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Urovant Sciences GmbH

External identifiers

EU CT number

2024-513995-16-00

EudraCT number

2021-000676-11

ClinicalTrials.gov

NCT05491525

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic, Others

To evaluate the efficacy of QD vibegron administration in pediatric subjects 2 years to < 18 years with NDO

Secondary objectives 2

1. To evaluate safety and tolerability of vibegron in pediatric subjects 2 years to < 18 years with NDO; - To evaluate the PK profile of vibegron after multiple-dose administration in pediatric subjects 2 years to < 18 years with NDO
2. To evaluate the pharmacokinetic (PK) profile of vibegron after multiple-dose administration in pediatric subjects 2 years to < 18 years with NDO

Conditions and MedDRA coding

Neurogenic Detrusor Overactivity (NDO)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001414-PIP02-21

Plan to share IPD

No

IPD plan description

Based on the draft Statistical Analysis Plan (SAP) and current regulatory plans, all study analysis will be via datasets and there is currently no reason (at this time) to provide individual analysis as part of registrational data release.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male or female participants, age 2 years to < 18 years at the Screening Visit. Participants age 12 to < 18 years (Cohort 1) must weigh at least 29.5 kilograms (kg). Participants age 2 to < 12 years (Cohort 2) must weigh at least 11 kg
2. 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.
3. 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 18

1. Participant has cerebral palsy, uncontrolled epilepsy, diabetes insipidus, or Stage 2 hypertension
2. Participant has an active malignancy in the 12 months prior to the Screening Visit.
3. Participant has been administered intravesical botulinum toxin within 9 months prior to the Screening Visit and should remain off this therapy during the study.
4. Participant is taking digoxin or lithium within 10 days prior to Screening Visit or plans to start taking either during the study.
5. Participant currently uses or plans to use a baclofen pump during the study.
6. Participant has urethral dilatation or has had urethral surgery in the 3 months prior to the Screening Visit
7. Participant has undergone bladder augmentation surgery
8. 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.
9. 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.
10. 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.
11. Participant has fecal impaction or a history of fecal impaction requiring hospitalization or ambulatory surgical treatment in the 3 months prior to the Screening Visit.
12. Participant has a urinary indwelling catheter in the 4 weeks prior to the Screening Visit
13. Participant has moderate to severe dilating vesicoureteral reflux (Grade III to V) or severe renal failure.
14. Participant started electrostimulation/neuromodulation therapy in the 4 weeks before the Screening Visit, or is expected to start this therapy during the study period.
15. Participant has participated in another clinical trial and/or has taken an investigational drug within 4 weeks prior to the Screening Visit.
16. Participant is unable, or parent/caregiver is not willing, to washout any medication for the management of NDO.
17. 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.
18. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline at Study Week 32 (Optimized Treatment Week 24) in MCC based on filling urodynamics

Secondary endpoints 5

1. Secondary Efficacy Endpoints: Based on Urodynamics: - Change from baseline at Study Week 20 (Optimized Treatment Week 12) in MCC - Change from baseline at Study Weeks 20 and 32 (Optimized Treatment Week 12 and 24) in: Number of overactive detrusor contractions until end of filling; Detrusor pressure at end of filling; Filling volume until first involuntary/hyperactive detrusor contraction; Bladder compliance
2. Secondary Efficacy Endpoints: Based on Bladder Diary: - Change from baseline at Study Weeks 1, 4, 8, 20, 32, 48, and 52 in: 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; Estimated number of dry days/7 days
3. Secondary Efficacy Endpoints: Based on Questionnaires: - Change from baseline at Study Weeks 20, 32, and 52 in PIN-Q - Change from baseline at Study Weeks 20, 32, and 52 in PGI-S Scale - CGI-C Scale assessment at Study Weeks 20, 32, and 52.
4. Safety and Tolerability: - Incidence of AEs - Incidence of AESIs - Upper urinary tract ultrasound assessment - eGFR - Vital signs measured at clinic visits: pulse rate, systolic and diastolic blood pressure - 12-lead ECG, centrally read
5. Pharmacokinetics: - PK of vibegron in plasma: Cmax, tmax, AUC(0-24h), Ctrough, t1/2, and CL/F

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sumitomo Pharma America Inc.

Sponsor organisation

Sumitomo Pharma America Inc.

Address

84 Waterford Drive

City

Marlborough

Postcode

01752-7010

Country

United States

Scientific contact point

Organisation

Urovant Sciences GmbH

Contact name

Vice-President, Medical Affairs & International Supply

Public contact point

Organisation

Urovant Sciences GmbH

Contact name

Vice-President, Medical Affairs & International Supply

Locations

9 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 179 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications