A Phase 3b Multicenter Open-label Trial of the Safety, Tolerability, and Efficacy of Tolvaptan in Infants and Children 28 days to less than 12 weeks of Age with Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Otsuka Pharmaceutical Development & Commercialization Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

completed 10 Dec 2025

Decision date (initial)

2024-05-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-508217-17-00

EudraCT number

2020-005991-36

ClinicalTrials.gov

NCT04786574

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effect of tolvaptan on the need for RRT in pediatric subjects with ARPKD.

Secondary objectives 2

1. Evaluate changes in eGFR and palatability and acceptability of formulation.
2. To evaluate the pharmacodynamics, safety, tolerability, and efficacy of tolvaptan in pediatric subjects with ARPKD.

Conditions and MedDRA coding

Autosomal Recessive Polycystic Kidney Disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001231-PIP02-13

Plan to share IPD

Yes

IPD plan description

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing. Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data. Otsuka will share data supported by the protocol, statistical analysis plan (SAP) and clinical study report (CSR) on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male or female subjects between 28 days and < 12 weeks of age, inclusive.
2. Must have clinical and imaging features that are consistent with a diagnosis of ARPKD with all the following characteristics: Nephromegaly (> 2 standard deviations from age-appropriate standard via ultrasound) Multiple renal cysts History of oligohydramnios or anhydramnios.
3. Ability for parent/legal guardian to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.

Exclusion criteria 23

1. Premature birth (≤ 32 weeks gestational age).
2. Has or at risk of having significant hypovolemia (eg, subjects that lack free access to water, without adequate fluid monitoring and management) as determined by investigator.
3. Severe systolic dysfunction defined as ejection fraction < 14%.
4. Serum sodium levels < 130 mmol/L or >145 mmol/L (or the ULN of the local laboratory, whichever is lower).
5. Clinically significant anemia, as determined by investigator.
6. Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation.
7. Evidence of syndromic conditions associated with renal cysts (other than ARPKD).
8. Abnormal liver function tests including ALT and AST, > 1.2 × ULN.
9. Parents with renal cystic disease.
10. Receiving chronic diuretic that could not be adjusted after tolvaptan initiation.
11. Cannot be monitored for fluid balance.
12. Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator.
13. Taking any other experimental medications.
14. Require ventilator support.
15. Taking medications known to induce CYP3A4.
16. Having an active infection including viral that would require therapy disruptive to IMP dosing.
17. Platelet count <50,000 µL.
18. Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).
19. Subjects who have bladder dysfunction and/or difficulty voiding.
20. Subjects taking a vasopressin agonist (eg, desmopressin).
21. Subjects having concomitant illnesses or taking medications likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, vasopressin antagonists, anti-sense RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).
22. History of cholangitis.
23. Received or are scheduled to receive a liver transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Efficacy: Percentage of subjects having RRT by 1 year of age

Secondary endpoints 8

1. Main secondary efficacy endpoint: Rate of change of eGFR (eGFR Schwartz formula = 0.413 × height [or length, cm] /serum creatinine mg/dL) from pretreatment to post‑treatment after 2 years of treatment.
2. Age-appropriate assessment of palatability and acceptability of suspension formulation.
3. Change in sNa+ from baseline at each visit.
4. Percentage of change in kidney size of height adjusted TKV at every time point from baseline to 24 months of treatment via ultrasound using ellipsoid methodology.
5. Change from baseline (last assessment prior to dosing) in growth percentile trajectories for height (stature), weight, and head circumference at 3 months, 6 months, 12 months, 18 months, and 24 months.
6. Summary of vital signs data.
7. Adverse events (AEs), including rate of aquaretic AEs.
8. Changes from baseline in serum creatinine and laboratory values including liver function tests (total bilirubin, ALT, AST, ALP, GGT).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Otsuka Pharmaceutical Development & Commercialization Inc.

Sponsor organisation

Otsuka Pharmaceutical Development & Commercialization Inc.

Address

2440 Research Boulevard

City

Rockville

Postcode

20850-3238

Country

United States

Scientific contact point

Organisation

Otsuka Pharmaceutical Development & Commercialization Inc.

Contact name

Olga Sergeyeva

Public contact point

Organisation

Otsuka Pharmaceutical Development & Commercialization Inc.

Contact name

Leslyn Hermonstine

Third parties 19

Locations

4 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 88 files

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

Application history

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