Autosomal Recessive Polycystic Kidney Disease (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 12 Weeks of Age With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
The primary objective of this study is to evaluate the effect of tolvaptan on the need for renal replacement therapy in pediatric subjects with autosomal recessive polycystic kidney disease (ARPKD)
| Status | Recruiting |
| Enrollment | 20 |
| Est. completion date | October 11, 2027 |
| Est. primary completion date | October 11, 2027 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 28 Days to 12 Weeks |
| Eligibility | Inclusion Criteria: 1. Male or female subjects between 28 days and < 12 weeks of age, inclusive at the time of enrollment. 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 or 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: 1. Premature birth (= 32 weeks gestational 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 5. Parents with renal cystic disease 6. Need for chronic diuretic use 7. Cannot be monitored for fluid balance 8. Has or at risk of having sodium and potassium electrolyte imbalances 9. Has or at risk of having significant hypovolemia as determined by investigator 10. Clinically significant anemia, as determined by investigator 11. Severe systolic dysfunction defined as ejection fraction < 14% 12. Serum sodium levels < 130 mmol/L or >145 mmol/L 13. Taking any other experimental medications 14. Require ventilator support 15. Taking medications known to induce CYP3A4 16. Having an infection including viral that would require therapy disruptive to IMP dosing 17. Platelet count <50,000 µL 18. Significant Portal Hypertension 19. Bladder dysfunction or difficulty voiding 20. Taking vasopressin agonist 21. Having concomitant illness or taking medications that are likely to confound endpoint assessments. 22. History of cholangitis 23. Received or scheduled to receive a liver transplant |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Universitair Ziekenhuis Gent | Gent | Oost-Vlaanderen |
| Belgium | UZ Leuven | Leuven | |
| Germany | University Hospital of Cologne | Cologne | Nordrhein-Westfalen |
| Poland | Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa | Bialystok | |
| Poland | Instytut "Pomnik - Centrum Zdrowia Dziecka" | Warszawa | |
| Spain | Hospital Universitari Vall D Hebron | Barcelona | |
| Spain | Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB) | Barcelona | |
| Spain | Hospital Universitario Virgen del Rocio | Sevilla | |
| United Kingdom | Great Ormond Street | London | |
| United States | C.S. Mott Children's Hospital | Ann Arbor | Michigan |
| United States | Emory University | Atlanta | Georgia |
| United States | Johns Hopkins Pediatric Specialty Clinic | Baltimore | Maryland |
| 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 | Cincinnati | Ohio |
| United States | Cleveland Clinic | Cleveland | Ohio |
| United States | Mayo Clinic | 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, Germany, Poland, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The percentage of subjects that will have Renal Replacement Therapy (RRT) by 1 year of age. | From Enrollment to 1 year of age | ||
| Secondary | Rate of change of eGFR by Schwartz formula from pre-treatment to after 2 years of treatment | From Enrollment to 2 years of age | ||
| Secondary | Palatability of the suspension formulation as assessed by a parent questionnaire immediately after and within 15-20 minutes after the first oral dose | From Enrollment to 2 years of age | ||
| Secondary | Acceptance of the suspension formulation as assessed by a parent questionnaire immediately after and within 15-20 minutes after the first oral dose | From Enrollment to 2 years of age |