PODOMOUNT-Basket, a Study to Test Whether BI 764198 Helps Adults and Adolescents With Different Types of Kidney Disease

Официальное название

PODOMOUNT-Basket, a Phase II, Multicentre, Randomised, 2-arm Parallel-group, Double-blind, Placebo-controlled Basket Trial to Assess Safety, Tolerability, PK, and Efficacy of BI 764198 in Four Proteinuric Kidney Diseases

Обзор

This study is open to adults with certain kidney conditions, including secondary focal segmental glomerulosclerosis (sFSGS), treatment-resistant primary minimal change disease (TR-pMCD), Alport Syndrome (AS), and treatment-resistant primary membranous nephropathy (TR-pMN). Adolescents with treatment-resistant primary MCD can also participate in this study. The purpose of this study is to find out whether a medicine called BI 764198 helps people with these kidney conditions. Participants are put into 2 groups randomly, which means by chance. One group takes BI 764198 tablets, and the other group takes placebo tablets. Placebo tablets look like BI 764198 tablets but do not contain any medicine. Participants take a tablet once a day for 20 weeks. All participants also continue their standard medication for their kidney condition during the study. Participants have twice the chance of being placed in the BI 764198 group than in the placebo group. Participants are in the study for about 7 months. During this time, they visit the study site 6 times and have 3 phone calls. Doctors regularly test the protein levels in participants' urine by collecting urine samples. They also check kidney function by taking blood samples. The results are compared between the two groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Вмешательства

• Препарат BI 764198
  BI 764198
• Препарат Placebo matching BI 764198
  Placebo matching BI 764198

Первичные конечные точки

• Relative change from baseline to Week 20 in 24-hr Urine protein-to-Creatinine Ratio (UPCR) [Срок оценки: At baseline and week 20]

Вторичные конечные точки (3)

• Treatment response, defined as at least 25% relative reduction in 24-hr UPCR from baseline to Week 20 [Срок оценки: At baseline and week 20]
• Treatment response, defined as at least 40% relative reduction in 24-hr UPCR from baseline to Week 20 [Срок оценки: At baseline and week 20]
• Absolute change in estimated glomerular filtration rate (eGFR) in mL/min/1.73m2 (based on cystatin C) from baseline to Week 20 [Срок оценки: At baseline and week 20]

Критерии участия

Критерии включения

• Male or female participants ≥18 years of age (≥12 years of age for Treatment resistant primary Minimal Change Disease (TR-pMCD)) on the day of signing informed consent/assent (Visit 1)
• Body Mass Index (BMI) of ≤40 kg/m2 at screening visit (Visit 1)
• Weight of ≥40 kg at screening
• Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 (chronic kidney disease (CKD) EPI formula based on serum cystatin C) at screening visit

• For adult participants (≥18); ≥25 mL/min/1.73 m2 (CKD-EPI formula based on serum cystatin C) at the screening visit
• For adolescent participants (<18); ≥25 mL/min/1.73 m2 (chronic kidey disease under 25 years (CKiD U25) formula using height and serum cystatin C) at the screening visit
• Seated blood pressure (mean of 3 values) systolic blood pressure (SBP) ≤160 mmHg (adult participants ≥18) or SBP ≤140 mmHg (participants <18) at the screening visit (Visit 1). A participant with a documented history of white coat hypertension may be included as long as the participant is considered medically stable by the investigator and "true" blood pressure can be considered to be ≤160 mmHg (adult participants ≥18) or ≤140 mmHg (adolescent participants <18)
• Participants should be treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), at a stable optimised dose for at least 8 weeks prior to the screening visit (Visit 1), with no plan to change the dose until the end of the randomised treatment period (i.e. end of trial (EoT), Week 20) unless not tolerated or indicated as per the discretion of the investigator
• If treated with (non-steroidal) mineralocorticoid receptor antagonist (MRA), endothelin receptor antagonists (ERA), glucagon-like peptide-1 (GLP-1) or Sodium-glucose co-transporter-2 (SGLT2) inhibitors (SGLT2i), participants must be on a stable dose for at least 8 weeks prior to the screening visit (Visit 1), preferably with no plan to change the dose until the end of the randomised double-blind treatment period (i.e. EoT, Week 20)
• Participants treated with oral immunosuppressive therapy except glucocorticoids (e.g. Calcineurin inhibitor(s) (CNI), mycophenolate mofetil/-sodium, cyclophosphamide) must be on a stable dose for at least 12 weeks prior to the screening visit (Visit 1) with no plans to change their dose during the trial treatment period
• Patients treated/to be treated with oral glucocorticoids have to be at a dose ≤10 mg/d prednisolone or equivalent for ≥4 weeks prior to screening with no plan to increase the dose during the treatment period.

Further inclusion criteria apply.

Критерии исключения

• A history of organ transplantation or planned transplantation during the course of the study
• Use of intravenous immunosuppressive agents (e.g. cyclophosphamide, rituximab, obinutuzumab) in the past 6 months prior to screening visit (Visit 1)
• Participants in whom initiation of oral or IV immunosuppression is anticipated during the course of the trial
• Treatment with metformin or dofetilide (multidrug and toxin extrusion protein 1 (MATE1) substrates) within one week prior to randomisation visit (Visit 2) through 5 days after the EoT visit
• Treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (CYP3A4/5) within one week or 5 half-lives (whichever is longer) prior to randomisation visit (Visit 2)
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3X the upper limit of normal (ULN) at screening visit (Visit 1)
• Clinically significant laboratory abnormalities or medical conditions which pose a safety risk for the participant or may interfere with the trial objectives in the investigator's opinion (except for renal function tests or deviation of clinical laboratory values that are related to the podocytopathy in question) at screening visit
• QTc intervals (QTcF) greater than 450 ms in males or greater than 470 ms in females, or any other clinically relevant ECG findings (at the investigator's discretion) at screening visit (Visit 1) Further exclusion criteria apply.

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 · 25 центров

• Nephrology Consultants, LLC — Huntsville
• Kidney Disease Medical Group — Glendale
• Amicis Research Center - Balboa — Granada Hills
• Academic Medical Research Institute - Glendale — Los Angeles
• University of California Los Angeles — Los Angeles
• Colorado Kidney Care — Denver
• Florida Kidney Physicians - Boca Raton — Boca Raton
• Florida Kidney Physicians, LLC - Fort Lauderdale — Fort Lauderdale
• … и ещё 17 центров

Китай · 12 центров

• Peking University First Hospital — Пекин
• Beijing Tsinghua Changgung Hospital — Пекин
• West China Hospital, Sichuan University — Чэнду
• Guangdong Provincial People's Hospital — Гуанчжоу
• The First Affiliated Hospital of Nanchang University — Nanchang
• Zhongda Hospital Southeast University — Нанкин
• The First People's Hospital of Nanning — Nanning
• Ruijin Hospital Shanghai Jiao Tong University School of Medicine — Шанхай
• … и ещё 4 центра

Индия · 9 центров

• Aartham Multi Super Speciality Hospital — Ahmedabad
• AIIMS Bhubaneshwar — Bhubaneswar
• Osmania Medical College & Hospital — Hyderabad
• … и ещё 6 центров

Италия · 8 центров

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Германия · 6 центров

• Vivantes Klinikum im Friedrichshain — Berlin
• Universitätsklinikum Köln (AöR) — Cologne
• Universitätsklinikum Hamburg, Eppendorf — Hamburg
• Medizinische Hochschule Hannover — Hanover
• Universitätsmedizin der Johannes Gutenberg-Universität Mainz — Mainz
• Klinikum rechts der Isar der Technischen Universität München — München

Япония · 6 центров

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Мексика · 6 центров

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Turkey (Türkiye) · 6 центров

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Бразилия · 5 центров

• Universidade Federal do Ceara — Fortaleza
• Hospital de Clinicas de Porto Alegre — Porto Alegre
• Fundacao Oswaldo Ramos (Hospital do Rim) — São Paulo
• Hospital das Clínicas da Faculdade de Medicina da USP — São Paulo
• Instituto da Crianca e do Adolescente — São Paulo

Хорватия · 5 центров

• Specijalna Bolnica Medico — Rijeka
• General Hospital Vinkovci — Vinkovci
• Clinical Hospital Sveti Duh — Zagreb
• Solmed Polyclinic — Zagreb
• University Hospital Dubrava — Zagreb

Франция · 5 центров

• CHU Amiens-Picardie — Amiens
• HOP Pellegrin — Bordeaux
• Hopital Henri Mondor — Créteil
• Hopital Pasteur — Nice
• Hopital Necker — Paris

Польша · 5 центров

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Португалия · 5 центров

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Словакия · 5 центров

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Испания · 5 центров

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Аргентина · 4 центра

• Terapia Renal Domiciliaria — Buenos Aires
• Centro Medico Dra Laura Maffei — Ciudad Autonoma Buenos Aires
• Clinica Privada Velez Sarfield — Córdoba
• CardioAlem Investigaciones — San Isidro

Австралия · 4 центра

• Nepean Hospital — Kingswood
• John Hunter Hospital — New Lambton Heights
• Royal Brisbane and Women's Hospital — Brisbane
• Princess Alexandra Hospital — Woolloongabba

Бельгия · 4 центра

• AZORG Ziekenhuis — Aalst
• Hopital Erasme — Brussels
• Az Maria Middelares Gent — Ghent
• UZ Leuven — Leuven

Норвегия · 4 центра

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Тайвань · 4 центра

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Великобритания · 4 центра

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Канада · 3 центра

• CaRe Clinic (Calgary) — Calgary
• Victoria Hospital (LHSC) — London
• Maisonneuve-Rosemont Hospital — Monteral

Малайзия · 3 центра

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Швеция · 3 центра

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Греция · 2 центра

• University General Hospital of Heraklion — Heraklion
• General University Hospital of Patras — Pátrai

Нидерланды · 2 центра

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Новая Зеландия · 2 центра

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Румыния · 2 центра

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Сингапур · 2 центра

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South Korea · 2 центра

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Дания · 1 центр

• Zealand University Hospita; Roskilde — Roskilde

Эстония · 1 центр

• Tartu University Hospital — Tartu

Швейцария · 1 центр

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Идентификаторы

NCT: NCT07355296 · 1434-0027 · 2025-523425-17 · U1111-1328-7108

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗