A Study to Learn More About How Well the Study Treatment Finerenone Works, How Safe it is, How it Moves Into, Through, and Out of the Body, and the Effects it Has on the Body When Taken With an ACE Inhibitor or Angiotensin Receptor Blocker in Children With Chronic Kidney Disease and Proteinuria

Официальное название

A 6-month Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and PK/PD of an age-and Body Weight-adjusted Oral Finerenone Regimen, in Addition to an ACEI or ARB, for the Treatment of Children, 6 Months to <18 Years of Age, With Chronic Kidney Disease and Proteinuria

Обзор

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 improve kidney function by helping the renin-angiotensin-aldosterone system (RAAS) to work normally. 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 stop the kidneys from working 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 more about whether finerenone added to either ACEI or ARB can help reduce the amount of protein in the participants' urine more than a placebo. A placebo looks like a treatment but does not have any medicine in it. Participants will also continue to receive their other medications. To see how the treatment work, the doctors will take samples of the participants' urine to measure their protein levels before and during taking treatment and after their last treatment. In addition, blood samples will be taken to monitor kidney function, electrolytes and the amount of finerenone in the blood as well as for other tests. This study will include children with CKD and proteinuria aged from 6 months up to less than 18 years. The participants will take: * either finerenone or the placebo, in addition to * either ACEI or ARB, whichever they take as part of their normal treatment Two visits are required up to 104 days, to check whether a child can take part in the treatment phase of the study. If participants qualify for the treatment phase, they will then undergo treatment for about 180 days. During this time, they will visit the study site at least 7 times. During these visits, the participants 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 guardians answer * answer questions about how they are feeling, or have their parents or guardians answer * answer question about how they like the study medication, or have their parents or guardians 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.

Вмешательства

• Препарат Finerenone (Kerendia, BAY94-8862)
  Finerenone in different doses, treatment duration will be 180±7 days
• Препарат Placebo
  Placebo to finerenone, treatment duration will be 180±7 days

Первичные конечные точки

• Percent change in Urinary protein-to-creatinine ratio (UPCR) reduction from baseline to day 180+/-7 [Срок оценки: From baseline to day 180+/-7]

Вторичные конечные точки (10)

• Number participants with treatment emergent adverse events (TEAEs） [Срок оценки: From the start of study intervention to last study intervention + 3 days (up to 190 days)]
• Change in serum potassium levels from baseline to day 180±7 [Срок оценки: From baseline to day 180±7]
• Change in serum creatinine from baseline to day 180±7 [Срок оценки: From baseline to day 180±7]
• Change in eGFR from baseline to day 180±7 [Срок оценки: From baseline to day 180±7]
• Change in systolic blood pressure from baseline to day 180±7 [Срок оценки: From baseline to day 180±7]
• UPCR reduction of at least 30% from baseline to day 180+/-7 [Срок оценки: From baseline to day 180±7]
• Change in UACR from baseline to day 180±7 [Срок оценки: From baseline to day 180±7]
• Pharmacokinetics (PK) finerenone Cmax, md [Срок оценки: Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7]
• Pharmacokinetics (PK) finerenone AUCτ,md [Срок оценки: Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7]
• Taste and texture questionnaire of the pediatric formulation [Срок оценки: On day 30±3 and day 180±7]

Критерии участия

Критерии включения

• Participants must be 6 months to <18 years old at the time when the informed consent/assent is signed
• Participants must have a clinical diagnosis of chronic kidney disease (CKD) at screening which is defined as

• CKD stages 1-3 (eGFR ≥30 mL/min/1.73m\^2) for children ≥1 year to <18 years of age or
• a serum creatinine ≤ 0.40 mg/dL for infants 6 months to < 1 year of age and
• severely increased proteinuria as defined by

• Urinary protein-to-creatinine ratio (UPCR) of ≥ 0.50 g/g in participants ≥ 2 years with CKD stage 2 and 3 or
• UPCR ≥ 1.0 g/g for patients < 2 years of age or ≥ 2 years of age and with CKD stage 1
• Participants must have stable kidney function between screening and D0 defined as:

• For participants with a creatinine of > 0.8 mg/dL at screening: no increase or decrease in eGFR by ≥ 20% at D0
• For participants with a creatinine of ≤ 0.8 mg/dL at screening: no increase or decrease in creatinine ≥ 0.15 mg/dL at D0.
• 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 management, unchanged for at least 30 days prior to screening
• K+ ≤5.0 mmol/L for children ≥2 years of age at both screening and D0, and ≤5.3 mmol/L for children <2 years of age at both screening and D0

Критерии исключения

• Planned urological surgery expected to influence renal function
• Children with hemolytic uremic syndrome (HUS) diagnosed ≤6 months prior to screening
• Patients with nephrotic syndrome receiving albumin infusions within the last 6 months prior to screening
• Patients who are candidates for renal transplantation, i.e., a kidney transplantation scheduled within the study time frame
• Renal allograft in place
• Bilateral renal artery stenosis
• Acute kidney injury requiring dialysis within 6 months prior to screening
• Systemic hypertension stage 2 in children ≥1 year of age defined according to guidelines on blood pressure management at screening or randomization
• Systolic blood pressure (SBP) above 110 mmHg in infants 6 months to <1 year of age at screening or randomization
• Systemic hypotension defined as a systolic blood pressure below the 5th percentile for age, sex and height at either screening or randomization but no lower than 80 mmHg (although for some participants the 5th percentile of SBP is < 80 mmHg they must be excluded if their SBP is <80 mmHg)
• Participants with immune-mediated CKD using rituximab, cyclophosphamide, abatacept, or high-dose glucocorticoids, within <6 months prior to screening

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 19 центров

• Phoenix Children's Hospital | Main - Transplant Department — Phoenix
• Cedars-Sinai Medical Center - Nephrology — Los Angeles
• Lucille Packard Children's Hospital Stanford - Pediatric Nephrology — Palo Alto
• UC San Diego - Altman Clinical and Translational Research Institute (ACTRI) - Linda Vista — San Diego
• Children's National Hospital - Nephrology — Washington D.C.
• Memorial Transplant Institute - Pediatric Nephrology — Hollywood
• Emory University Hospital/Children's Healthcare of Atlanta - Nephrology — Atlanta
• University of Iowa Health Care Medical Center - Nephrology — Iowa City
• … и ещё 11 центров

Германия · 8 центров

• Universitätsklinikum Heidelberg — Heidelberg
• Universitätsklinikum Erlangen AöR — Erlangen
• Medizinische Hochschule Hannover (MHH) — Hanover
• Kindernierenzentrum Bonn — Bonn
• Universitätsklinikum Essen — Essen
• Universitätsklinikum Münster — Münster
• Charité / Pädiatrie — Berlin
• Universitätsklinikum Hamburg Eppendorf (UKE) — Hamburg

Turkey (Türkiye) · 8 центров

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Польша · 7 центров

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Аргентина · 6 центров

• Instituto Universitario Hospital Italiano de Buenos Aires | Hospital Italiano de Buenos Ai — Ciudad Autonoma de Buenos Aire
• Hospital General de Ninos Ricardo Gutierrez | Pediatric Nephrology Department — Ciudad Autonoma de Buenos Aire
• Centro de Rehabilitacion Cardiovascular | San Luis, Argentina — San Luis
• Clinica de Nefrologia, Urologia y Enfermedades Cardiovascualares | Santa Fe, Argentina — Santa Fe
• Hospital de Pediatría Juan P. Garrahan — Buenos Aires
• Hospital General de Ninos Pedro de Elizalde | Nephrology Department — Buenos Aires

Бразилия · 6 центров

• Hospital Pequeno Principe — Curitiba
• Hosp Clínicas Facult. Med. de Ribeirão Preto / USP — Ribeirão Preto
• Hospital Infantil Sabará - Instituto PENSI - Pesquisa e Ensino em Saúde Infantil — São Paulo
• Instituto da Crianca e do Adolescente — São Paulo
• Hospital PUC-Campinas | Centro de Pesquisa Clínica Sao Lucas — São Paulo
• Santa Casa de Misericórdia de Belo Horizonte — São Paulo

Франция · 6 центров

• CHU de Lyon - Hopital Femme Mère Enfant — Bron
• CHU Strasbourg - Hopital Hautepierre — Strasbourg
• CHU bordeaux - Hopital Pellegrin — Bordeaux
• Hopital Arnaud de Villeneuve CHU Montpellier — Montpellier
• Hôpital des Enfants — Toulouse
• Hopital Robert Debre — Paris

Индия · 6 центров

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Италия · 6 центров

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Мексика · 6 центров

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Испания · 6 центров

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Тайвань · 6 центров

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Бельгия · 5 центров

• Huderf / Ukzkf — Bruxelles - Brussel
• CU Saint-Luc/UZ St-Luc — Bruxelles - Brussel
• UZ Gent — Ghent
• UZ Gasthuisberg - Pediatric Nephrology — Leuven
• CHC Montlégia - Pediatrics — Liège

Греция · 5 центров

• Children's Hospital of Athens P&A Kyriakou - Pediatric Nephrology Department — Athens
• Children's Hospital of Athens Agia Sofia - Pediatric Nephrology Department — Athens
• University General Hospital of Heraklion — Heraklion
• University General Hospital Of Ioannina-Child Health Sector — Ioannina
• Ippokratio General Hospital Of Thessaloniki-Pediatric Nephrology Unit, 3rd Department of P — Thessaloniki

Израиль · 5 центров

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Малайзия · 5 центров

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South Korea · 5 центров

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Великобритания · 5 центров

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Австралия · 4 центра

• The Children's Hospital at Westmead — Westmead
• Queensland Children's Hospital — South Brisbane
• Monash Children's Hospital — Clayton
• Royal Children's Hospital Melbourne — Parkville

Австрия · 4 центра

• Uniklinikum Salzburg - Landeskrankenhaus — Vienna
• Medizinische Univ Graz | Kinder & Jugendheilkunde — Graz
• Kepler Universitätsklinikum Campus IV — Innsbruck
• AKH Wien | Kinder & Jugendheilkunde, Kindernephrologie — Vienna

Канада · 4 центра

• Alberta Children's Hospital | Nephrology Clinic — Calgary
• McMaster University Medical Centre | McMaster Children's Hospital | Cardiology — Hamilton
• The Hospital for Sick Children (SickKids) — Toronto
• Centre hospitalier universitaire Sainte-Justine | Cardiology — Montreal

Венгрия · 4 центра

• Pecsi Tudomanyegyetem Klinikai Kozpont — Pécs
• Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ — Szeged
• … и ещё 2 центра

Португалия · 4 центра

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Болгария · 3 центра

• UMHAT Sveti Georgi — Plovdiv
• SHATPD "Prof. Ivan Mitev" — Sofia
• MHAT prof. Stoyan Kirkovitch AD — Stara Zagora

Дания · 3 центра

• Rigshospitalet - Børn og Unge — Copenhagen
• Aarhus Universitetshospital - Børn og Unge — Aarhus N
• Odense Universitetshospital - HC Andersen Børne og Ungehospital — Odense

Финляндия · 3 центра

• Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS) - Lasten lääketutki — Tampere
• Turun yliopistollinen keskussairaala — Turku
• HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Uusi lastensairaala, nefrologia — Helsinki

Литва · 3 центра

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Нидерланды · 3 центра

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Швеция · 3 центра

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Швейцария · 3 центра

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Чехия · 2 центра

• Všeobecná fakultní nemocnice v Praze — Prague
• Fakultní nemocnice Motol a Homolka, Pracovište MOTOL — Prague

ЮАР · 1 центр

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Публикации

• Schaefer F, Montini G, Kang HG, Walle JV, Zaritsky J, Schreuder MF, Litwin M, Scalise A, Scott H, Potts J, Iveli P, Breitenstein S, Warady BA. Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies. Trials. 2024 Mar 21;25(1):203. doi: 10.1186/s13063-024-08021-z. PMID 38509517

Идентификаторы

NCT: NCT05196035 · 19920 · 2023-504884-17-00 · 2021-002071-19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗