Clinical trial NCT04786574: 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)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Keywords: ARPKD
Tolvaptan
Polycystic Kidney Disease
Autosomal Recessive Polycystic Kidney Disease
Renal Cysts
Nephromegaly
Oligohydramnios
Anhydramnios
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-08
Enrollment: 20
Sex: ALL
Minimum age (years): 28
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The percentage of subjects that will have Renal Replacement Therapy (RRT) by 1 year of age.
timeFrame: From Enrollment to 1 year of age
Secondary outcomes:
measure: Rate of change of eGFR by Schwartz formula from pre-treatment to after 2 years of treatment
timeFrame: From Enrollment to 2 years of age
measure: Palatability of the suspension formulation as assessed by a parent questionnaire immediately after and within 15-20 minutes after the first oral dose
timeFrame: From Enrollment to 2 years of age
measure: Acceptance of the suspension formulation as assessed by a parent questionnaire immediately after and within 15-20 minutes after the first oral dose
timeFrame: From Enrollment to 2 years of age
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago - Neonatology
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Pediatric Specialty Clinic
state: Maryland
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven
city: Cologne
country: Germany
facility: University Hospital of Cologne
state: Nordrhein-Westfalen
city: Białystok
country: Poland
facility: Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
city: Warszawa
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka"
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D Hebron
city: Barcelona
country: Spain
facility: Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: London
country: United Kingdom
facility: Great Ormond Street
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Olga Sergeyeva, MD
role: STUDY_DIRECTOR
References: