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)

• ClinicalTrials.gov Identifier: NCT04786574
• Recruitment Status: Not yet recruiting
• First Posted: March 8, 2021
• Last Update Posted: March 8, 2021
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Autosomal Recessive Polycystic Kidney Disease (ARPKD)	Drug: Tolvaptan (OPC-41061)	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Estimated Study Start Date: April 1, 2021
• Estimated Primary Completion Date: March 31, 2025
• Estimated Study Completion Date: July 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tolvaptan (OPC-41061)	Drug: Tolvaptan (OPC-41061); 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.

Outcome Measures

Primary Outcome Measures :

1. The percentage of subjects that will have RRT by 1 year of age. [ Time Frame: From Enrollment to 1 year of age ]

Secondary Outcome Measures :

1. Rate of change of eGFR by Schwartz formula from pre-treatment to after 2 years of treatment [ Time Frame: From Enrollment to 2 years of age ]
2. Acceptance and palatability of the suspension formulation will be assessed by a parent questionnaire immediately after and within 15-20 minutes after the first oral dose [ Time Frame: From Enrollment to 2 years of age ]

Eligibility Criteria

• Ages Eligible for Study: up to 12 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female subjects between 28 days and < 12 weeks of age, inclusive.

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
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. Critical electrolyte imbalances, as determined by the investigator
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
13. Cannot be 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

Contacts and Locations

Contacts

Contact: Lindsay Getz; (919) 797-9591; lindsay.getz@paidion.com

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

• Study Director: Rosa Real, MD; Otsuka Pharmaceutical Development & Commercialization, Inc.

More Information

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT04786574
• Other Study ID Numbers: 156-12-204
• First Posted: March 8, 2021
• Last Update Posted: March 8, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

ARPKD; Tolvaptan; Polycystic Kidney Disease; Autosomal Recessive Polycystic Kidney Disease; Renal Cysts; Nephromegaly; Oligohydramnios; Anhydramnios

Additional relevant MeSH terms:

Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Recessive; Urologic Diseases; Kidney Diseases, Cystic; Abnormalities, Multiple; Congenital Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Tolvaptan; Antidiuretic Hormone Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Physiological Effects of Drugs