New Clinical Trial Underway to Evaluate Safety of Tolvaptan in Pediatric ARPKD Patients

A multinational, multicenter phase 3 clinical trial is in progress to evaluate the safety and efficacy of the drug Tolvaptan in treating infants and children with autosomal recessive polycystic kidney disease (ARPKD). The study officially launched in July 22 and is currently recruiting participants at 19 sites.

UPMC Children’s Division of Pediatric Nephrology is one of the participating centers. clinical Division Clinical Director and Medical Director of Pediatric Dialysis, Michael L. Moritz, MD, FASN, is the site principal investigator at UPMC Children’s.

“There are currently no effective treatments for ARPKD. Tolvaptan has proven to be beneficial in autosomal dominant polycystic kidney disease (ADPKD), and it will be important to know if these benefits will extend to ARPKD,” says Dr. Moritz.

What is ARPKD?

ARPKD is a rare autosomal genetic disorder that primarily affects infants and children. Caused by mutations in the PKHD1 gene, the condition typically involves the development of numerous fluid-filled cysts in the kidneys that lead to chronic kidney disease and progressive renal failure. ARPKD disrupts normal kidney function, often resulting in decreased urine-concentrating ability, high blood pressure, and end-stage renal disease. ARPKD also commonly affects the patient’s liver and functionality by inducing fibrosis and portal hypertension.

What is Tolvaptan?

Tolvaptan is a selective vasopressin V2-receptor antagonist, typically used to manage hyponatremia, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Tolvaptan functions by increasing the excretion of free water from the body without significantly affecting electrolytes. Tolvaptan has shown promise in slowing the progression of ADPKD by reducing the growth rate of kidney cysts, preserving kidney function over time. While the drug is approved for use in adults for the conditions above, it has yet to be tested and approved for use in pediatric patients with ARPKD.

Trial Details and Aims

The primary objective of this study is to assess the safety of tolvaptan in pediatric patients, with treatment-emergent adverse events (TEAEs) being the primary outcome measure. The secondary outcomes include the annual rate of change of estimated glomerular filtration rate (eGFR) after 18 months, changes in eGFR at specific monthly intervals, the percentage of subjects requiring renal replacement therapy (RRT), and the duration between enrollment and RRT.

Participants will be assigned to either tolvaptan suspension or tablets, with varying dosages based on the participant’s age and weight. Treatment with tolvaptan suspension will be administered orally or via feeding/nasogastric tube, while tolvaptan tablets will be administered orally as split-dose regimens based on weight.

Refer a Patient to UPMC Children’s

Primary care physicians and treating nephrologists are encouraged to consider referring suitable pediatric patients for this promising study. This trial represents a significant step in understanding and potentially improving treatment options for children suffering from ARPKD.

For additional information about the study, or to make a patient referral refer to UPMC Children’s, please contact the Division at 412-692-5182.