Back to Trials
NCT04782258PHASE3Recruiting

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)

Otsuka Pharmaceutical Development & Commercialization, Inc.

Start Date

1/23/2023

Completion Date

8/14/2028

Summary

To evaluate the pharmacodynamics and safety of tolvaptan in pediatric subjects with 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 24 months over the course of the study. The overall trial duration is expected to be approximately 4.1 years.

Eligibility Criteria

Age Range: No minimum to 18 years

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 (Investigational Medicinal Product) 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). 28. Subjects who do not agree to remain abstinent or assent to use a combination of 2 of the following highly effective birth control methods for at least 28 days before the first dose of IMP, during the trial (including during IMP dose interruptions), and for at least 30 days after the last dose of IMP: * Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide * Intrauterine device * Hormone-based contraceptives which are associated with inhibition of ovulation.

Interventions

DRUG

Tolvaptan Suspension

DRUG

Tolvaptan Tablets

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Autosomal Recessive Polycystic Kidney (ARPKD)

Locations

Children's National Medical Center

Washington D.C., District of Columbia 20010

United States

Emory University Hospital

Atlanta, Georgia 30322

United States

Northwestern University Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago - Neonatology

Chicago, Illinois 60611

United States

Riley Hospital for Children

Indianapolis, Indiana 46202-5119

United States

Children's Hospital - New Orleans

New Orleans, Louisiana 70118

United States

Johns Hopkins Pediatric Specialty Clinic

Baltimore, Maryland 21287

United States

C.S. Mott Children's Hospital

Ann Arbor, Michigan 48109-5000

United States

Mayo Clinic - Rochester

Rochester, Minnesota 55905

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229-3039

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania 15213

United States

Primary Children's Hospital

Salt Lake City, Utah 84113

United States

Université Catholique De Louvain And Cliniques St Luc

Brussels, Brussels Capital 1200

Belgium

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen 9000

Belgium

UZ Leuven

Leuven, Vlaams Brabant 3000

Belgium

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia 50937

Germany

Instytut "Pomnik - Centrum Zdrowia Dziecka"

Warsaw, Masovian Voivodeship 04-730

Poland

Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa

Bialystok, 15-274

Poland

Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB)

Esplugues de Llobregat, Barcelona 8950

Spain

Hospital Universitari Parc Tauli

Sabadell, Barcelona 08208

Spain

Hospital Universitari Vall D Hebron

Barcelona, 8035

Spain

Hospital Universitario Virgen del Rocío Avenida Manuel Siurot

Seville, 41013

Spain

Great Ormond Street Hospital for Children NHS Trust

London, WC1N 3JH

United Kingdom