A study to learn how effective and safe the drug “mirabegron” is and how long it stays in the body of children aged 6 months to less than 3 years of age with neurogenic detrusor overactivity

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Biological Phenomena [G16]

Trial duration

28 Feb 2024 → 12 Dec 2025

Decision date (initial)

2023-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astellas Pharma Global Development Inc.

External identifiers

EU CT number

2023-507903-74-00

EudraCT number

2021-005455-37

ClinicalTrials.gov

NCT05621616

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy, Safety

To evaluate the efficacy of mirabegron prolonged-release microgranula-based suspension after multiple dose administration in the pediatric population.

Secondary objectives 3

1. To evaluate the additional efficacy of mirabegron prolonged-release microgranula-based suspension
2. To evaluate the safety and tolerability of mirabegron prolonged release microgranula-based suspension after multiple-dose administration.
3. To evaluate the PK of mirabegron prolonged-release microgranula-based suspension after multiple-dose administration

Conditions and MedDRA coding

Neurogenic detrusor overactivity (NDO)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000597-PIP03-15

Plan to share IPD

No

IPD plan description

Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas’ data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. IRB/IEC approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for US study sites) must be obtained from the participant’s LAR prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. 2. Participant is male or female and 6 months to less than 3 years of age.
3. 3. Participant’s weight is a minimum of 9 kg.
4. 4. Participant has a previous myelomeningocele (documented at the screening visit).
5. 5. Participant has a diagnosis of NDO confirmed by urodynamic investigation at baseline (day 1). The diagnosis of NDO should be confirmed by the presence of ≥ 1 involuntary detrusor contraction > 15 cm H2O from baseline detrusor pressure, and/or a decrease in bladder compliance leading to an increase in baseline detrusor pressure of > 20 cm H2O.
6. 6. Participant has a diagnosis of DSD.
7. 7. Participant is using CIC.
8. 8. Participant is suitable for a regimen of 4 to 6 CICs per day, fixed for the duration of the study in the opinion of the investigator using the 7-day baseline e-diary.
9. 9. Participant is able to swallow the study drug.
10. 10. Participant’s LAR is willing and able to comply with the study requirements (including compliant use of the e-diary) and with the concomitant medication restrictions.
11. 11. Participant’s LAR agree not to allow participant to participate in another interventional study while receiving study intervention and throughout the pretreatment period.

Exclusion criteria 25

1. 1. Participant has a bladder capacity less than 25% of expected age-related capacity, confirmed by urodynamic investigation at baseline (day 1).
2. 2. Participant has vesicoureteral reflux grade 3 to 5 in the opinion of the investigator.
3. 3. Participant has a known genitourinary condition, other than NDO, that may cause overactive contractions and/or incontinence (e.g., bladder exstrophy, urinary tract obstruction, urethral diverticulum or fistula) or kidney/bladder stones or another persistent local pathology that may cause urinary symptoms.
4. 4. Participant has had an indwelling urinary catheter within 4 weeks prior to the baseline visit.
5. 5. Participant has undergone bladder augmentation surgery.
6. 6. Participant with surgically corrected underactive sphincter.
7. 7. Participant receives electrostimulation therapy, if started within 30 days before visit 1 screening or is expected to start during the study period. Participants who are on an established regimen (defined as starting more than 30 days before visit 1 screening) may remain on this for the duration of the study.
8. 8. Participant has been administered intravesical botulinum toxin; except if given > 4 months prior to visit 1 screening and the participant experiences symptoms comparable to those existing prior to the botulinum toxin injections.
9. 9. Participant has a current symptomatic UTI confirmed by urinalysis (urine culture containing > 100,000 cfu/mL) at baseline. If at screening and start of washout a UTI is present, the participant will be eligible for enrollment if the UTI has been treated successfully prior to baseline. If a symptomatic UTI is present at baseline, all baseline assessments should be postponed for a maximum of 7 days until the UTI is successfullu treated. Successful treatment is defined as a symptom free patient with a white blood cell count in the urine < 100/microliter and urine culture below 100,000 cfu/mL.
10. 10. Participant is using prohibited medications listed in [Section 10.5].
11. 11. Participant has a diagnosis of central or congenital nephrogenic diabetes insipidus.
12. 12. Participant with severe gastrointestinal (GI) condition (including toxic megacolon) or any of the following GI conditions: partial or complete obstruction, decreased motility like paralytic ileus or at risk for gastric retention.
13. 13. Participant suffers from malnutrition or is severely overweight, in the opinion of the investigator. See [Section 10.8.1].
14. 14. Participant has an average QTcB > 440 ms (based on the QTcB mean from the screening and baseline ECG triplicates), history of QTc prolongation or risk of QT prolongation (e.g., hypokalemia, LQTS, or family history of LQTS, exercise induced syncope).
15. 15. Participant has severe renal impairment (eGFR < 30 mL/min per 1.73 m2 for participants 1 year of age and older; serum creatinine ≥ 2 × ULN, with ULN defined as 97.5th percentile, for participants 6 to < 12 months of age [Table 9; Boer et al, 2010]).
16. 16. Participant’s AST or ALT is ≥ 2 × ULN or TBL greater than or equal to 1.5 × ULN.
17. 17. Participant has a current or previous history of epilepsy
18. 18. Participant has a history or presence of any malignancy prior to visit 1 screening.
19. 19. Participant has any other clinically significant out of range results of urinalysis, biochemistry, hematology or coagulation as per the investigator’s interpretation.
20. 20. Participant has an established hypertension and systolic or diastolic blood pressure greater than the 99th percentile of their normal range determined by gender, body size and age, plus 5 mmHg (reference for normal blood pressure for children < 1 year old is [Report of the second task force on blood pressure control in children, 1987] and for children ≥ 1 years old is [Flynn et al, 2017]).
21. 21. Participant has a (median) resting heart rate > 99th percentile [Section 10.7.3].
22. 22. Participant has any clinically significant or unstable medical condition or disorder which, in the opinion of the investigator, precludes the participant from participating in the study.
23. 23. Participant has known or suspected hypersensitivity to mirabegron, any of the excipients used in the current formulation or previous severe hypersensitivity to any drug.
24. 24. Participant has participated in another clinical trial and/or has taken an investigational drug within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1 screening.
25. 25. Participant is being breast-fed by a woman taking any prohibited medication or fed with a milk product in which the presence of prohibited medication ingredients cannot be excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in MCC after 24 weeks of study intervention (based on filling urodynamics)

Secondary endpoints 10

1. Change from baseline in urodynamic measures: o Bladder compliance (ΔV/ΔP) at weeks 4 and 24 o Filling volume until first detrusor contraction (> 15 cm H2O) at weeks 4 and 24 o Number of uninhibited detrusor contractions until leakage or until maximum 135% of age-related bladder capacity
2. Change from baseline in e-diary measures: o Maximum and average catheterized daytime volume o Average morning catheterized volume (based on first catheterization after participant woke up) o Number of leakage episodes (per 24 h) o Number of dry (leakage-free) days per 7 days
3. Acceptability by P-OMAQ-C at weeks 4, 24, and 52
4. AEs
5. Vital signs, on site and SBPM; SBPM from baseline to EOS
6. Clinical laboratory tests (hematology, coagulation, biochemistry, eGFR, urinalysis)
7. 12-lead ECG
8. Upper urinary tract ultrasound
9. AUC24, Ctrough, CL/F, VZ/F, Cmax and Tmax
10. Additional PK parameters may be calculated based on the model used

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6111

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head Regulatory Affairs

Third parties 8

Locations

4 EU/EEA countries · 5 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 45 files

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

Application history

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