Autosomal Recessive Polycystic Kidney (ARPKD) Clinical Trial
Official title:
A Phase 3b Multicenter Open-label Trial of the Safety, Tolerability, and Efficacy of Tolvaptan in Infants and Children 28 Days to Less Than 18 Years of Age With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
The primary objective of this study is to evaluate the safety of tolvaptan in pediatric subjects with autosomal recessive polycystic kidney disease (ARPKD)
| Status | Recruiting |
| Enrollment | 10 |
| Est. completion date | April 27, 2026 |
| Est. primary completion date | April 27, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 28 Days to 18 Years |
| Eligibility | Inclusion Criteria: 1. Male or female subjects between 28 days and less than 18 years of age, with clinical features that are consistent with a diagnosis of ARPKD. 2. 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. Ability to provide written informed assent from all subjects old enough per local laws to provide assent. Exclusion Criteria: 1. Premature birth (= 32 weeks gestational age) for infants 28 days to < 12 weeks of age. 2. Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation. 3. Evidence of syndromic conditions associated with renal cysts (other than ARPKD). 4. Abnormal liver function tests including ALT and AST, > 1.2 × ULN (upper limit of normal). 5. Has splenomegaly or portal hypertension (HTN). 6. Parents with renal cystic disease. 7. Receiving chronic diuretic that could not be adjusted after tolvaptan initiation. 8. Cannot be monitored for fluid balance. 9. Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator. 10. Has or at risk of having significant hypovolemia as determined by investigator. 11. Clinically significant anemia, as determined by investigator. 12. Platelets < 50000 µL. 13. Severe systolic dysfunction defined as ejection fraction < 14%. 14. Serum sodium levels < 130 mmol/L or >145 mmol/L. 15. Taking any other experimental medications. 16. Require ventilator support. 17. Taking medications known to induce CYP3A4 (CYP = Cytochrome P). 18. Having an infection including viral that would require therapy disruptive to IMP dosing. 19. Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP. 20. Subjects with a history of substance abuse (within the last 6 months). 21. Subjects who have bladder dysfunction and/or difficulty voiding. 22. Subjects taking a vasopressin agonist (eg, desmopressin). 23. Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy. 24. Subjects taking medications or having concomitant illnesses 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 ribonucleic acid (RNA) therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin). 25. Received or are scheduled to receive a liver transplant. 26. History of cholangitis within the last 6 months. 27. Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia). |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Université Catholique De Louvain And Cliniques St Luc | Brussels | Brussels Capital Region |
| Belgium | UZ Leuven | Leuven | Vlaams Brabant |
| France | Centre Hospitalier Universitaire de Bordeaux (CHU) - Groupe | Bordeaux | |
| Germany | University Hospital Cologne AöR | Cologne | Nordrhein-Westfalen |
| Italy | Istituto G.Gaslini, Istituto Pediatrico di Ricovero e Cura a | Genova | Liguria |
| Italy | Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico - Clinica De Marchi | Milano | |
| Poland | Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa | Bialystok | |
| United Kingdom | Great Ormond Street Hospital for Children NHS Trust | London | |
| United Kingdom | Central Manchester University Hospitals Nhs Foundation Trust | Manchester | |
| United States | Emory University Hospital | Atlanta | Georgia |
| United States | Northwestern University Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago - Neonatology | Chicago | Illinois |
| United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
| United States | Cleveland Clinic | Cleveland | Ohio |
| United States | Children's Hospital - New Orleans | New Orleans | Louisiana |
| United States | The Children's Hospital of Philadelphia (CHOP) | Philadelphia | Pennsylvania |
| United States | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania |
| United States | Mayo Clinic - Rochester | Rochester | Minnesota |
| United States | Primary Children's Hospital | Salt Lake City | Utah |
| United States | Children's National Medical Center | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Otsuka Pharmaceutical Development & Commercialization, Inc. |
United States, Belgium, France, Germany, Italy, Poland, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Enrollment up to 7 days post last dose | ||
| Secondary | Annual rate of change of eGFR (by Schwartz formula) from baseline to post-treatment after 18 months of treatment | From Enrollment to 18 months | ||
| Secondary | Change from baseline of eGFR (by Schwartz formula) while on treatment at Months 1, 6, 12, and 18 | 1 month, 6 months, 12 months, and 18 months | ||
| Secondary | The percentage of subjects that will receive renal replacement therapy (RRT) by 18 months. | From Enrollment to 18 months | ||
| Secondary | The amount of time between enrollment and 18 months that a subject requires renal replacement therapy (RRT). | From enrollment to 18 months |