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)

Description

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)Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (CKD stages 1 to 3), a closely related indication to ARPKD, as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV). The trial will be the first trial of tolvaptan in a pediatric ARPKD population. Participants in this study will be assigned to tolvaptan for 24 months and closely monitored over the course of the study.

Trial 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

Study Info

Interventions

Locations Recruiting

Interested in joining this trial?

Our dedicated patient navigators are here to guide you through the validation and enrollment process with ease.