Clinical trial NCT04782258: A Study to See if Tolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years 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 18 Years of Age With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Autosomal Recessive Polycystic Kidney (ARPKD)
Keywords: ARPKD
TOLVAPTAN
Polycystic Kidney Disease
Autosomal Recessive Polycystic Kidney Disease
Adolescent
Renal Cysts
Oligohydramnios
Anhydramnios
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-04
Enrollment: 20
Sex: ALL
Minimum age (years): 28
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety of tolvaptan in pediatric subjects with autosomal recessive polycystic kidney disease (ARPKD)

Detailed description: This study is a multinational, multicenter, open-label, non-randomized trial. The study consist of three periods: Screening Period, Treatment period and Follow-up period.

Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (CKD stages 1 to 4), a closely related indication to ARPKD, as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV).

Participants in this study will be assigned to tolvaptan and followed for 18 months over the course of the study.

The overall trial duration is expected to be approximately 3.5 years.

Eligibility criteria: Inclusion Criteria:

1. Male or female subjects between 28 days and less than 18 years of age, with clinical features that are consistent with a diagnosis of ARPKD.
2. Ability for parent/legal 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. Ability to provide written informed assent from all subjects old enough per local laws to provide assent.

Exclusion Criteria:

1. Premature birth (≤ 32 weeks gestational age) for infants 28 days to \< 12 weeks of 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 (upper limit of normal).
5. Has splenomegaly or portal hypertension (HTN).
6. Parents with renal cystic disease.
7. Receiving chronic diuretic that could not be adjusted after tolvaptan initiation.
8. Cannot be monitored for fluid balance.
9. Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator.
10. Has or at risk of having significant hypovolemia as determined by investigator.
11. Clinically significant anemia, as determined by investigator.
12. Platelets \< 50000 µL.
13. Severe systolic dysfunction defined as ejection fraction \< 14%.
14. Serum sodium levels \< 130 mmol/L or \>145 mmol/L.
15. Taking any other experimental medications.
16. Require ventilator support.
17. Taking medications known to induce CYP3A4 (CYP = Cytochrome P).
18. Having an infection including viral that would require therapy disruptive to IMP dosing.
19. Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP.
20. Subjects with a history of substance abuse (within the last 6 months).
21. Subjects who have bladder dysfunction and/or difficulty voiding.
22. Subjects taking a vasopressin agonist (eg, desmopressin).
23. Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.
24. Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, vasopressin antagonists, anti-sense ribonucleic acid (RNA) therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).
25. Received or are scheduled to receive a liver transplant.
26. History of cholangitis within the last 6 months.
27. Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).

Primary outcomes:
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Enrollment up to 7 days post last dose
Secondary outcomes:
measure: Annual rate of change of eGFR (by Schwartz formula) from baseline to post-treatment after 18 months of treatment
timeFrame: From Enrollment to 18 months
measure: Change from baseline of eGFR (by Schwartz formula) while on treatment at Months 1, 6, 12, and 18
timeFrame: 1 month, 6 months, 12 months, and 18 months
measure: The percentage of subjects that will receive renal replacement therapy (RRT) by 18 months.
timeFrame: From Enrollment to 18 months
measure: The amount of time between enrollment and 18 months that a subject requires renal replacement therapy (RRT).
timeFrame: From enrollment to 18 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Research Site #104
state: District of Columbia
city: Atlanta
country: United States
facility: Research Site #100
state: Georgia
city: Chicago
country: United States
facility: Research Site #108
state: Illinois
city: Indianapolis
country: United States
facility: Research Site #110
state: Indiana
city: New Orleans
country: United States
facility: Research Site #101
state: Louisiana
city: Baltimore
country: United States
facility: Research Site #113
state: Maryland
city: Ann Arbor
country: United States
facility: Research Site #111
state: Michigan
city: Rochester
country: United States
facility: Research Site #107
state: Minnesota
city: Cincinnati
country: United States
facility: Research Site #102
state: Ohio
city: Cleveland
country: United States
facility: Research Site #105
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site #103
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Research Site #106
state: Utah
city: Brussels
country: Belgium
facility: Research Site #301
state: Brussels Capital Region
city: Gent
country: Belgium
facility: Research Site #302
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: Research Site #300
state: Vlaams Brabant
city: Cologne
country: Germany
facility: Research Site #260
state: Nordrhein-Westfalen
city: Warszawa
country: Poland
facility: Research Site #361
state: Mazowieckie
city: Bialystok
country: Poland
facility: Research Site #360
city: Esplugues De Llobregat
country: Spain
facility: Research Site #561
state: Barcelona
city: Sabadell
country: Spain
facility: Research Site #562
state: Barcelona
city: Barcelona
country: Spain
facility: Research Site #560
city: Sevilla
country: Spain
facility: Research Site #563
city: London
country: United Kingdom
facility: Research Site #200
Study officials:
References: