A Study to See if Tolvaptan Can Delay Dialysis in Infants and Children Who at Enrollment Are 28 Days to Less Than 12 Weeks Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Study Overview
=================
Brief Summary
-----------------
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)

Detailed Description
-----------------
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.

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)

Conditions
-----------------
Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Intervention / Treatment
-----------------
* Drug: Tolvaptan (OPC-41061)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects between 28 days and < 12 weeks of age, inclusive at the time of enrollment. 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 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: Premature birth (≤ 32 weeks gestational age) Anuria or RRT, defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation Evidence of syndromic conditions associated with renal cysts (other than ARPKD) Abnormal liver function tests including ALT and AST, > 1.2 × ULN Parents with renal cystic disease Need for chronic diuretic use Cannot be monitored for fluid balance Has or at risk of having sodium and potassium electrolyte imbalances Has or at risk of having significant hypovolemia as determined by investigator Clinically significant anemia, as determined by investigator Severe systolic dysfunction defined as ejection fraction < 14% Serum sodium levels < 130 mmol/L or >145 mmol/L Taking any other experimental medications Require ventilator support Taking medications known to induce CYP3A4 Having an infection including viral that would require therapy disruptive to IMP dosing Platelet count <50,000 µL Significant Portal Hypertension Bladder dysfunction or difficulty voiding Taking vasopressin agonist Having concomitant illness or taking medications that are likely to confound endpoint assessments. History of cholangitis Received or scheduled to receive a liver transplant

Ages Eligible for Study
-----------------
Minimum Age: 28 Days
Maximum Age: 12 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolvaptan (OPC-41061)<br> | Drug: Tolvaptan (OPC-41061)<br>* Tolvaptan suspension will be administered orally or via nasogastric tube at doses of 0.15 mg/kg once daily in the AM, 0.30 mg/kg once daily in the AM, 0.5 mg/kg once daily in the AM, 0.75 mg/kg split dose (0.5 mg/kg AM and 0.25 mg/kg 8 hours later), and 1 mg/kg split dose (0.67 mg/kg AM and 0.33 mg/kg 8 hours later) based on age. Treatment duration is 2 years.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects that will have Renal Replacement Therapy (RRT) by 1 year of age. |  | From Enrollment to 1 year of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of change of eGFR by Schwartz formula from pre-treatment to after 2 years of treatment |  | From Enrollment to 2 years of age | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ARPKD, Tolvaptan, Polycystic Kidney Disease, Autosomal Recessive Polycystic Kidney Disease, Renal Cysts, Nephromegaly, Oligohydramnios, Anhydramnios