Clinical trial NCT05457283: A Study to Learn More About How Safe the Study Treatment Finerenone is in Long-term Use When Taken With an ACE Inhibitor or Angiotensin Receptor Blocker Over 18 Months of Use in Children and Young Adults From 1 to 18 Years of Age With Chronic Kidney Disease and Proteinuria
Official title: An 18-month, Open-label, Single-arm Safety Extension Study of an age-and Bodyweight-adjusted Oral Finerenone Regimen, in Addition to an ACEI or ARB, for the Treatment of Children and Young Adults From 1 to 18 Years of Age With Chronic Kidney Disease and Proteinuria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Kidney Disease
Proteinuria
Children
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2022-07-13
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Researchers are looking for a better way to treat children who have chronic kidney disease (CKD), which is long-term kidney disease, and proteinuria, a condition in which a person´s kidneys leak protein into the urine.

The kidneys filter waste and fluid from the blood to form urine. In children with CKD, the kidney´s filters do not work as well as they should. This can lead to accumulation of waste and fluid in the body and proteinuria. CKD can lead to other medical problems, such as high blood pressure, also known as hypertension. Vice versa, hypertension and proteinuria can also contribute to worsening of CKD. Therefore, the treatment of CKD aims to control blood pressure and proteinuria. There are treatments available for doctors to prescribe to children with CKD and hypertension and/or proteinuria. These include "angiotensin-converting enzyme inhibitors" (ACEI) and "angiotensin receptor blockers" (ARB). Both ACEI and ARB can help improve kidney function by reducing the activity of the renin-angiotensin-aldosterone system (RAAS). The RAAS is a system that works with the kidneys to control blood pressure and the balance of fluid and electrolytes in the blood. In people with CKD, the RAAS is often too active, which can impair the ability of the kidneys to work properly and cause hypertension and proteinuria. However, ACEI or ARB treatment alone does not work for all patients with CKD as they only target the angiotensin part of the renin-angiotensin-aldosterone system.

The study treatment, finerenone, is expected to help control RAAS overactivation together with an ACEI or ARB.

So, the researchers in this study want to learn more about whether finerenone given in addition to either an ACEI or ARB can help their kidney function.

The main purpose of this study is to learn how safe the treatment is when used of finerenone in addition to an ACEI or ARB in long-term.

To see how safe the treatment is, the study team will collect information on medical problems which are also known as "treatment emergent adverse events" (TEAEs). And they will also collect levels of an electrolyte called potassium in the blood by taking blood samples, and measure blood pressure during the study.

The secondary purpose of this study is to learn how well long-term use of finerenone can reduce the amount of protein in the participants' urine and benefit kidney function when taken with standard of care.

To see how the treatment works, the study team will collect participants' urine samples to assess urinary albumin-to-creatinine ratio (UACR) and urinary protein-to-creatinine ratio (UPCR), which are important assessments for calculating the level of protein in the urine. Researchers will also collect blood samples to analyze serum creatinine and calculate estimated glomerular filtration rate (eGFR). A significant decline in eGFR indicates worsening kidney function.

The study will include participants who had previously participated in FIONA study (NCT05196035). The participants will be aged from 1 year up to 18 years.

The participants will be in the study for approximately 19 months. They will take study treatment for up to 18 months and will be follow up for 1 month. During this period, at least 12 visits are planned for patients who newly start finerenone, and at least 8 visits for patients who already received finerenone.

In the visit, the study team will:

* have their blood pressure, heart rate, temperature, height and weight measured
* have blood and urine samples taken
* have physical examinations
* have their heart examined by an electrocardiogram and echocardiography (a sonogram of the heart)
* answer questions about their medication and whether they have any adverse events, or have their parents or guardian's answer
* answer questions about how they are feeling, or have their parents or guardian's answer
* answer question about how they like the study medication, or have their parents or guardian's answer The doctors will keep track of any adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

The doctors will check the participants' health about 30 days after the participants take their last treatment.


Eligibility criteria: Inclusion Criteria:

* Participants must be ≥1 year to 18 years of age, at the time of signing the informed consent/assent.
* Prior participation in the finerenone Phase 3 study FIONA (19920) and not permanently discontinued from treatment by the end of treatment (EoT) visit in FIONA.
* Participants must have a clinical diagnosis of chronic kidney disease (CKD) at Visit 1 which is defined as

  * CKD stages 1-3 (estimated glomerular filtration rate \[eGFR\] ≥30 mL/min/1.73m\^2) for children ≥1 year to \<19 years of age at FIONA EoT and at Visit 1
* Treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at optimized doses defined as maximally tolerable doses within the recommended dose range according to guidelines on blood pressure (BP) management, unchanged for at least 30 days prior to Visit 1.
* K+ ≤5.0 mmol/L for children ≥2 years of age at both FIONA EoT and Visit 1, and ≤5.3 mmol/L for children \<2 years of age at both FIONA EoT and Visit 1
* Participants who have reached legal age of consent: Capable of giving signed informed consent.
* Participant is able to receive enteral feeding (solid food, bottle or cup fed, feeding through nasogastric or gastric feeding tubes) with or without breastfeeding.

Exclusion Criteria:

* Planned urological surgery expected to influence renal function
* Patients who are candidates for renal transplantation, i.e., a kidney transplantation scheduled within the study time frame
* Systemic hypertension Stage 2 defined according to institutional guidelines on BP management at Visit 1.
* Systemic hypotension defined as symptomatic hypotension or a mean systolic BP below the 5th percentile for age, sex and height but no lower than 80 mmHg for participants \<18 years and symptomatic hypotension or a mean systolic blood pressure (SBP) \<90 mmHg in participants ≥18 years at Visit 1.
* Known hypersensitivity to the study treatment (active substance or excipients)
* Severe hepatic insufficiency defined by e.g. Child-Pugh C or analogous scores.
* Participants using rituximab, cyclophosphamide, abatacept, or intravenous glucocorticoids
* Concomitant therapy with a mineralocorticoid receptor antagonist (MRA)(eplerenone, spironolactone, esaxerenone, canrenone), any renin inhibitor (aliskiren, enalkiren, remikiren), any sodium-glucose co-transporter-2 (SGLT2) inhibitor (SGLT2i), sacubitril/valsartan combination (ARNI), or potassium-sparing diuretic (amiloride, triamterene)
* Concomitant therapy with both ACEI and ARBs together
* Concomitant therapy with strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors, moderate or strong CYP3A4 inducers
* Previous assignment to treatment during this study
* Simultaneous participation in another interventional clinical study (e.g., Phase 1 to 4 clinical studies).
* Any suspected (serious) adverse event related to study intervention which led to permanent discontinuation during the FIONA study.
* Pregnant or breastfeeding or intention to become pregnant during the study

Primary outcomes:
measure: Number of participants with treatment emergent adverse event (TEAEs)
timeFrame: Up to 550 days
measure: Change in serum potassium levels from baseline to Day 540±7
timeFrame: Up to 547 days
measure: Change in systolic blood pressure (SBP) from baseline to Day 540±7
timeFrame: Up to 547 days
Secondary outcomes:
measure: Change in urinary protein-to-creatinine ratio (UPCR) from baseline to Day 540±7
timeFrame: Up to 547 days
measure: Change in urinary albumin-to-creatinine ratio (UACR) from baseline to Day 540±7
timeFrame: Up to 547 days
measure: Change in estimated glomerular filtration rate (eGFR) from baseline to Day 540±7
timeFrame: Up to 547 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital | Main - Transplant Department
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Samuel Oschin Cancer Center
state: California
city: Palo Alto
country: United States
facility: Lucille Packard Children's Hospital Stanford - Pediatric Nephrology
state: California
city: Washington
country: United States
facility: Children's National Medical Center - Nephrology
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Transplant Institute - Pediatric Nephrology
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital/Children's Healthcare of Atlanta - Nephrology
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: The Charlotte R. Bloomberg Children's Center Building - Nephrology
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital - Main Campus - Nephrology
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital Kansas City - Nephrology
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center | Division of Nephrology and Hypertension
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic | Pediatric Nephrology
state: Ohio
city: Portland
country: United States
facility: OHSU Doernbecher Children's Hospital - Neurology
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Nephrology
state: Pennsylvania
city: San Antonio
country: United States
facility: Univ of Texas Health Science Center | Nephrology Res Dept
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital - Nephrology
state: Washington
city: La Plata
country: Argentina
facility: Hospital de Niños Sor María Ludovica
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aire
country: Argentina
facility: Hospital General de Ninos Ricardo Gutierrez | Pediatric Nephrology Department
state: Ciudad Auton. De Buenos Aires
city: San Luis
country: Argentina
facility: Centro de Rehabilitacion Cardiovascular | San Luis, Argentina
state: Provincia De San Luis
city: Santa Fe
country: Argentina
facility: Clinica de Nefrologia, Urologia y Enfermedades Cardiovascualares | Santa Fe, Argentina
state: Provincia De Santa Fe
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital de Pediatría Juan P. Garrahan
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital General de Ninos Pedro de Elizalde | Nephrology Department
city: Multiple Locations
country: Argentina
facility: Many Locations
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital Melbourne
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Campus IV
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Multiple Locations
country: Austria
facility: Many Locations
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg - Landeskrankenhaus
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Bruxelles - Brussel
country: Belgium
facility: Huderf / Ukzkf
city: Bruxelles - Brussel
country: Belgium
facility: CU Saint-Luc/UZ St-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg - Pediatric Nephrology
city: Liège
country: Belgium
facility: CHC Montlégia - Pediatrics
city: Multiple Locations
country: Belgium
facility: Many Locations
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de Belo Horizonte
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe
state: Parana
city: Ribeirão Preto/SP
country: Brazil
facility: Hosp Clínicas Facult. Med. de Ribeirão Preto / USP
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital PUC-Campinas | Centro de Pesquisa Clínica Sao Lucas
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Infantil Sabará - Instituto PENSI - Pesquisa e Ensino em Saúde Infantil
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto da Crianca e do Adolescente
city: Calgary
country: Canada
facility: Alberta Children's Hospital - Nephrology Clinic
state: Alberta
city: Toronto
country: Canada
facility: The Hospital for Sick Children (SickKids)
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Multiple Locations
country: Czechia
facility: Many Locations
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Børn og Unge
city: Multiple Locations
country: Denmark
facility: Many Locations
city: Odense C
country: Denmark
facility: Odense Universitetshospital - HC Andersen Børne og Ungehospital
city: Århus N
country: Denmark
facility: Aarhus Universitetshospital - Børn og Unge
city: Helsinki
country: Finland
facility: Helsinki University Hospital | Children's Hospital - Clinical Trial Unit, Nephrology Department
city: Multiple Locations
country: Finland
facility: Many Locations
city: Tampere
country: Finland
facility: Tays Service Centre | Tampere University Hospital - Pediatric Early Phase Clinical Trials Unit
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: BORDEAUX cedex
country: France
facility: CHU bordeaux - Hopital Pellegrin
city: Bron
country: France
facility: CHU de Lyon - Hopital Femme Mère Enfant
city: Montpellier
country: France
facility: Hopital Arnaud de Villeneuve CHU Montpellier
city: Multiple Locations
country: France
facility: Many Locations
city: Paris
country: France
facility: Hopital Robert Debre
city: Strasbourg
country: France
facility: CHU Strasbourg - Hopital Hautepierre
city: TOULOUSE Cedex 9
country: France
facility: Hôpital des Enfants
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH) | Zentrum Innere Medizin | Klinik fuer Kardiologie und Angiologie
state: Niedersachsen
city: Bonn
country: Germany
facility: Kindernierenzentrum Bonn
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Kindernierenzentrum Bonn
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitaetsklinikum Muenster
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité / Pädiatrie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf (UKE)
city: Multiple Locations
country: Germany
facility: Many Locations
city: Athens
country: Greece
facility: Children's Hospital of Athens P&A Kyriakou - Pediatric Nephrology Department
city: Athens
country: Greece
facility: Children's Hospital of Athens Agia Sofia - Pediatric Nephrology Department
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion - Department of Paediatrics
city: Ioannina
country: Greece
facility: Univ. General Hospital of Ioannina - Department of Paediatrics, Nephrology Unit
city: Multiple Locations
country: Greece
facility: Many Locations
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki - 3rd Department of Paediatrics, Nephrology Unit'
city: Budapest
country: Hungary
facility: Semmelweis University
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Multiple Locations
country: Hungary
facility: Many Locations
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
city: Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS) - New Delhi
city: Kolkata
country: India
facility: NRS Medical college
city: Beer Sheva
country: Israel
facility: Clalit Health | Soroka Medical Center - Internal Medicine Department
city: Jerusalem
country: Israel
facility: Wilf Children's Hospital Shaare Zedek Medical Center
city: Multiple Locations
country: Israel
facility: Many Locations
city: Nahariya
country: Israel
facility: Health Corporation of Galilee Medical Center
city: Petach Tikva
country: Israel
facility: Clalit Health Services Schneider Children's Medical Center
city: Tel Aviv
country: Israel
facility: Dana-Dwek Children's Hospital
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola - Pediatria
state: Emilia-Romagna
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - Nefrologia
state: Lazio
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini - Nefrologia e Trapianto Rene
state: Liguria
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Nefrologia e Dialisi Pediatrica, Trapianti di Rene
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Meyer IRCCS - Nefrologia e Dialisi
city: Multiple Locations
country: Italy
facility: Many Locations
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino_Regina Margherita - Nefrologia Pediatrica
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
state: Daegu Gwang''yeogsi
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggido
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnamdo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Multiple Locations
country: Korea, Republic of
facility: Many Locations
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Kaunas
country: Lithuania
facility: Hospital of LT University of Health Sciences Kaunas Clinics
city: Klaipeda
country: Lithuania
facility: Klaipeda Children's Hospital
city: Multiple Locations
country: Lithuania
facility: Many Locations
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos Children's Hospital Paediatrics Centre
city: Aguascalientes
country: Mexico
facility: Sitio Alfredo Chew Wong | Aguascalientes, Mexico
state: Agguascalientes
city: México D.F.
country: Mexico
facility: Hospital Infantil de México "Dr. Federico Gómez"
state: Distrito Federal
city: México, D.F.
country: Mexico
facility: Instituto Nacional de Pediatría
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Hospital Universitario "José Eleuterio González"
state: Nuevo Leon
city: Veracruz
country: Mexico
facility: Instituto Veracruzano en Investigación Clinica SC
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Multiple Locations
country: Netherlands
facility: Many Locations
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Bialystok
country: Poland
facility: Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Multiple Locations
country: Poland
facility: Many Locations
city: Warszawa
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka"
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
city: Missing
country: Portugal
facility: Hospital Santa Maria | Centro de Investigacao Clinica
state: Lisboa
city: Braga
country: Portugal
facility: Centro Clinico Academico Braga | Braga, Portugal
city: Coimbra
country: Portugal
facility: Hospital Pediátrico de Coimbra I ULS Coimbra
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto | Servico de Investigacao Clinica
city: Barcelona
country: Spain
facility: Ciutat Sanitaria i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital la Paz
city: Multiple Locations
country: Spain
facility: Many Locations
city: Málaga
country: Spain
facility: Hospital Universitario Regional De Malaga - Nefrologia pediatrica
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio S.L. - Nefrologia pediatrica
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Multiple Locations
country: Sweden
facility: Many Locations
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Basel
country: Switzerland
facility: Universitäts-Kinderspital UKBB
state: Basel-Stadt
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
city: Geneva
country: Switzerland
facility: Hopital des Enfants HUG
city: Multiple Locations
country: Switzerland
facility: Many Locations
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Baskent Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Health Ministry Of Türkiye Republic Ankara Bilkent City Hospital
city: Istanbul
country: Turkey
facility: Istanbul Faculty of Medicine, Department of Internal Medicine, Department of Pediatrics
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa - Cocuk Nefrolojisi
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty | Pediatric Nephrology
city: Multiple Locations
country: Turkey
facility: Many Locations
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde | Royal Hospital for Children - Glasgow Clinical Research Facility
state: Stratchclyde
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Multiple Locations
country: United Kingdom
facility: Many Locations
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
Study officials:
References: