PMID- 38509517
OWN - NLM
STAT- MEDLINE
DCOM- 20240322
LR  - 20240323
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 25
IP  - 1
DP  - 2024 Mar 21
TI  - Investigating the use of finerenone in children with chronic kidney disease and 
      proteinuria: design of the FIONA and open-label extension studies.
PG  - 203
LID - 10.1186/s13063-024-08021-z [doi]
LID - 203
AB  - INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease 
      (CKD) progression in children. Finerenone, a selective, non-steroidal, 
      mineralocorticoid receptor antagonist (MRA) has been approved to treat adults 
      with CKD associated with type 2 diabetes mellitus (T2DM) following results from 
      the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD 
      (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), 
      finerenone was shown to have an acceptable safety profile and was efficacious in 
      decreasing the risk of adverse kidney and cardiovascular outcomes and of 
      proteinuria. OBJECTIVE: FIONA and the associated open-label extension (OLE) study 
      aim to demonstrate that combining finerenone with an angiotensin-converting 
      enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, 
      well-tolerated, and effective in sustainably reducing urinary protein excretion 
      in children with CKD and proteinuria. DESIGN: FIONA (NCT05196035; Eudra-CT: 
      2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, 
      multicenter, phase III study of 6 months' duration in approximately 219 pediatric 
      patients. Patients must have a clinical diagnosis of CKD (an 
      eGFR >/= 30 mL/min/1.73 m(2) if >/= 1 to < 18 years or a serum creatinine 
      level </= 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria 
      despite ACEi or ARB usage. The primary objective is to demonstrate that 
      finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary 
      protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) 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. FIONA has 
      two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction 
      of >/= 30% from baseline to day 180 and percent change in UPCR from baseline to day 
      180. 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. CONCLUSION: FIONA is evaluating the use of finerenone in 
      children with CKD and proteinuria. Should safety, tolerability, and efficacy be 
      demonstrated, finerenone could become a useful additional therapeutic agent in 
      managing proteinuria and improving kidney outcomes in children with CKD. TRIAL 
      REGISTRATION: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.
CI  - (c) 2024. The Author(s).
FAU - Schaefer, Franz
AU  - Schaefer F
AUID- ORCID: 0000-0001-7564-9937
AD  - Pediatric Nephrology Division, Heidelberg University Hospital, Heidelberg, 
      Germany. Franz.Schaefer@med.uni-heidelberg.de.
FAU - Montini, Giovanni
AU  - Montini G
AUID- ORCID: 0000-0002-7350-4475
AD  - Department of Clinical Sciences and Community Health, University of Milan, Milan, 
      Italy.
AD  - Department of Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione 
      IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Kang, Hee Gyung
AU  - Kang HG
AD  - Department of Pediatrics, Seoul National University College of Medicine, Seoul, 
      South Korea.
FAU - Walle, Johan Vande
AU  - Walle JV
AD  - Department of Pediatric Nephrology, Ghent University Hospital, Erknet Center, 
      C4C, Ghent, Belgium.
FAU - Zaritsky, Joshua
AU  - Zaritsky J
AD  - Department of Nephrology, Phoenix Children's Hospital, Phoenix, AZ, USA.
FAU - Schreuder, Michiel F
AU  - Schreuder MF
AD  - Department of Pediatric Nephrology, Radboudumc Amalia Children's Hospital, 
      Nijmegen, The Netherlands.
FAU - Litwin, Mieczyslaw
AU  - Litwin M
AD  - Department of Nephrology and Arterial Hypertension, Children's Memorial Health 
      Institute, Warsaw, Poland.
FAU - Scalise, Andrea
AU  - Scalise A
AD  - Bayer Hispania, S.L, Sant Joan Despi, Barcelona, Spain.
FAU - Scott, Helen
AU  - Scott H
AD  - Bayer U.S Pharmaceuticals, Whippany, NJ, USA.
FAU - Potts, James
AU  - Potts J
AD  - Bayer U.S Pharmaceuticals, Whippany, NJ, USA.
FAU - Iveli, Pablo
AU  - Iveli P
AD  - Bayer AG, Wuppertal, Germany.
FAU - Breitenstein, Stefanie
AU  - Breitenstein S
AD  - Bayer AG, Wuppertal, Germany.
FAU - Warady, Bradley A
AU  - Warady BA
AD  - Department of Pediatrics, University of Missouri-Kansas City School of Medicine, 
      Kansas City, MO, USA.
AD  - Children's Mercy Kansas City, Kansas City, MO, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT05196035
GR  - 777389/Innovative Medicines Initiative 2 Joint Undertaking (JU)/
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20240321
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
RN  - 0 (finerenone)
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (Naphthyridines)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Child
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Angiotensin Receptor Antagonists/therapeutic use
MH  - Angiotensin-Converting Enzyme Inhibitors/adverse effects
MH  - *Renal Insufficiency, Chronic/complications/diagnosis/drug therapy
MH  - Proteinuria/drug therapy/chemically induced
MH  - Mineralocorticoid Receptor Antagonists/adverse effects
MH  - *Diabetic Nephropathies/drug therapy
MH  - *Naphthyridines
PMC - PMC10956186
OTO - NOTNLM
OT  - Chronic kidney disease
OT  - Finerenone
OT  - Mineralocorticoid
OT  - Pediatric
OT  - Proteinuria
OT  - Renoprotective therapy
COIS- The authors wrote the article with the assistance of a medical writer funded by 
      the sponsor. The sponsor was involved in the study design and the writing of the 
      report. FS discloses consultant fees for Amgen, Bayer, GSK, Otsuka, and Roche, 
      and advisory committee fees for Alnylam and Bayer. GM discloses advisory 
      committee fees for Alynlam, Bayer, and Chiesi Farmaceutici. JVW discloses 
      advisory committee and consultant fees from Bayer. MFS discloses consultant fees 
      from Bayer and Travere Therapeutics. ML has nothing to disclose. JZ discloses 
      speaker honoraria (including speakers' bureau, symposia, and expert witness) for 
      Alnylam, Horizon, and Natera, and advisory board fees for Bayer and Kaneka. AS, 
      HS, JAP, PI, and SB are Bayer employees. BAW discloses consultant fees from 
      Amgen, Roche, and GSK.
EDAT- 2024/03/21 06:43
MHDA- 2024/03/22 06:44
PMCR- 2024/03/21
CRDT- 2024/03/21 00:46
PHST- 2023/12/05 00:00 [received]
PHST- 2024/02/26 00:00 [accepted]
PHST- 2024/03/22 06:44 [medline]
PHST- 2024/03/21 06:43 [pubmed]
PHST- 2024/03/21 00:46 [entrez]
PHST- 2024/03/21 00:00 [pmc-release]
AID - 10.1186/s13063-024-08021-z [pii]
AID - 8021 [pii]
AID - 10.1186/s13063-024-08021-z [doi]
PST - epublish
SO  - Trials. 2024 Mar 21;25(1):203. doi: 10.1186/s13063-024-08021-z.