50 - Use of Finerenone in Children with Chronic Kidney Disease and Proteinuria: Design of the FIONA and Open-Label Extension Studies

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 50
Publication Number: 50.35

Joshua Zaritsky, University of Florida Health, Gainesville, FL, United States; Franz Schaefer, Heidelberg University Hospital, Heidelberg, Baden-Wurttemberg, Germany; Giovanni Montini, University of Milano, Milano, Lombardia, Italy; Hee G. Kang, Seoul National University College of Medicine, Seoul, Seoul-t'ukpyolsi, Republic of Korea; Johan GJ. vande Walle, University Hospital Ghent, GENT, Oost-Vlaanderen, Belgium; Michiel F. Schreuder, Radboudumc Amalia Children's Hospital, Nijmegen, Gelderland, Netherlands; Mieczysław Litwin, The Children's Memorial Health Institute, Warsaw, Mazowieckie, Poland; Andrea Scalise, BAYER HISPANIA S.L, Barcelona, Catalonia, Spain; Helen Scott, Bayer Pharmaceuticals, Whippany, NJ, United States; James A.. Potts, Bayer U.S. Pharmaceuticals, Whippany, NJ, United States; Pablo Iveli, Bayer AG, Bonn, Nordrhein-Westfalen, Germany; Stefanie Breitenstein, Bayer AG, Wuppertal, Nordrhein-Westfalen, Germany; Brad A. Warady, Children's Mercy, Kansas City, MO, United States

Presenting Author(s)

Joshua Zaritsky, MD, PhD (he/him/his)

Pediatric Nephrologist
University of Florida Health
Gainesville, Florida, United States

Background:

Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone (FIN), a selective, nonsteroidal, mineralocorticoid receptor antagonist has been approved to treat adult patients (pts) with CKD associated with type 2 diabetes mellitus (T2DM) following results from phase III clinical trials (FIDELIO-DKD [NCT02540993] and FIGARO-DKD [NCT02545049]). In a prespecified pooled analysis of both studies (n=13026), FIN was safe and efficacious in decreasing the risk of kidney and cardiovascular outcomes as well as proteinuria. Based on results in adults with CKD and T2DM, it is anticipated that combining FIN with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) will exert comparable beneficial effects on urinary protein excretion and kidney function in children with CKD and proteinuria.

Objective:

FIONA and the associated open-label extension study (FIONA OLE) aim to demonstrate that combining FIN with an ACEi or ARB is safe, well tolerated and efficacious in sustainably reducing urinary protein excretion in children with CKD and proteinuria.

Design/Methods:

FIONA (NCT05196035) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in ∼219 pediatric pts (Figure 1). Pts must have a clinical diagnosis of CKD and proteinuria, despite ACEi and ARB usage (Table 1). The primary objective is to demonstrate that FIN added to an ACEi or ARB is superior to placebo in reducing protein excretion (Table 2). FIONA OLE (NCT05457283) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data (Table 2).

Results:

Enrolment for FIONA follows an age-staggered approach and started in March 2022, with the adolescent cohort (aged 12 to < 18 years). First pts were successfully transitioned to FIONA OLE in Nov 2022. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥30% from baseline to day 180±7 and percent change in UPCR from baseline to day 180±7. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. The primary endpoints for FIONA OLE are listed in Table 2.

Conclusion(s):

FIONA will evaluate the use of FIN in children with CKD and proteinuria. Should safety, tolerability and efficacy be demonstrated, FIN could become a useful addition in managing proteinuria and improving kidney outcomes in children with CKD.