A Study to Find Out How EMPAgliflozin is Tolerated and if it Helps Children and Adolescents With Chronic KIDNEY Disease (EMPA-KIDNEY® Kids)

Official title

A Randomised, Double-blind, Placebo-controlled Trial With an Open-label Extension to Assess the Pharmacokinetics, Safety, and Efficacy of Empagliflozin Tablets in Paediatric Patients With Chronic Kidney Disease (EMPA-KIDNEY® Kids)

Overview

This study is open to children aged 2 to 17 with chronic kidney disease (CKD). The purpose of this study is to find out if a medicine called empagliflozin helps children and adolescents with CKD. Other goals of the study are to find out how empagliflozin is tolerated and handled by the body in children and adolescents with CKD. Participants are put into 2 groups randomly, which means by chance. One group takes empagliflozin and the other group takes placebo. Placebo looks like empagliflozin but does not contain any medicine. Participants are twice as likely to be in the empagliflozin group. Participants take empagliflozin or placebo as tablets once a day for 6 months. After 6 months, participants in both groups take empagliflozin as tablets once a day for 1 year. Participants are in the study for a little over a year and a half. During this time, they visit the study site about 15 times and get at least 5 phone or video calls from the site staff. At the visits, the doctors take blood and urine samples from the participants. The doctors also regularly check participants' health and take note of any unwanted effects.

Interventions

• Drug Empagliflozin
  Empagliflozin
• Drug Placebo
  Placebo

Primary outcome measures

• Change from Day 1 to the Week 24 visit in urine albumin-creatinine (UACR) [mg/g] [Time frame: Up to week 24]
• Change from Day 1 to the Week 24 visit in urine glucose [mmol/L] [Time frame: Up to week 24]

Secondary outcome measures (5)

• Change in estimated glomerular filtration rate (eGFR) (U25Crea) over time during treatment with empagliflozin [Time frame: Up to week 73]
• Annual rate of change in eGFR (U25Crea) from the Week 8 to the Week 24 visit, including treatment effect extrapolation from (adult) EMPA-KIDNEY data [Time frame: Up to week 24]
• Change from Day 1 to the Week 24 visit in urine protein-creatinine ratio (UPCR) [Time frame: Up to week 24]
• The observed predose plasma concentrations of empagliflozin at the Week 26 visit [Time frame: Up to week 26]
• Occurrence of at least one SAE or AE of special interest (AESI) per participant between Day 1 and the Week 24 visit, and between the Week 24 visit and end of treatment (EoT) +7 days residual effect period (REP) [Time frame: Up to week 73]

Eligibility criteria

Inclusion criteria

• Signed and dated written informed consent provided by the patient's parent(s) (or legal guardian) and patient's assent in accordance with international council for harmonisation good clinical practice (ICH-GCP) and local legislation prior to admission to the trial (informed assent will be sought according to the patient's age, level of maturity, competence, and capacity).
• Age 2 to 17 years at screening Visit 1.
• Chronic kidney disease (CKD) of any underlying aetiology defined by (as measured by central laboratory at screening Visit 1): estimated glomerular filtration rate (eGFR) (U25Crea) ≥20 to <90 mL/min/1.73 m2 with a urine-albumine-creatinine (UACR) ≥300 mg/g
• Participants must be on a stable dose of maximally tolerated standard of care (SoC) therapy for 30 days before screening visit 1 with no plans to change the dose throughout the duration of the placebo-controlled duration of the trial. SoC is anticipated to include a single Renin-angiotensin-aldosterone system (RAAS) inhibitor, such as angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi) as appropriate and tolerated. Additional use of a mineralocorticoid receptor antagonist (MRA, including finerenone if available) is permitted if needed and the dose is stable for 30 days before screening Visit 1 and no planned dose changes for the placebo-controlled portion of the trial.
• Participants receiving daily immunosuppressive therapy for an underlying immunological cause of CKD must be on a stable dose for the duration specified for each drug prior to screening and must remain on a stable regimen throughout the placebo-controlled portion of the trial.
• Further inclusion criteria apply.

Exclusion criteria

• Confirmed type 1 or type 2 diabetes mellitus.
• History of ketoacidosis within 8 weeks prior to Visit 1 and up to randomisation.
• Chronic dialysis or functioning kidney transplant or scheduled for transplantation throughout the duration of the trial.
• Diagnosis of uncontrolled metabolic bone disease (at the Investigator's discretion).
• Body mass index (BMI) ≤10th percentile for children ≥4 years of age and ≤25th percentile for children <4 years of age according to Centers for Disease Control and Prevention (CDC) growth chart at screening Visit 1.
• Gastrointestinal disorders that might interfere with trial drug absorption according to investigator assessment.
• Presence of acute or active urinary tract infection (UTI) with signs or symptoms of an active UTI or therapeutic treatment for an active UTI within 14 days before screening Visit 1.
• Severe, uncontrolled hypertension (based on investigator's judgement).
• Further exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 30 centers

• University of Alabama at Birmingham — Birmingham
• Phoenix Children's Hospital — Phoenix
• University of California Los Angeles — Los Angeles
• Stanford University School of Medicine — Palo Alto
• University of California Davis — Sacramento
• University of California San Francisco — San Francisco
• University of Miami — Miami
• Emory University — Atlanta
• … and 22 more centers

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

France · 6 centers

• Hôpital Louis Pradel — Bron
• HOP Timone — Marseille
• HOP Enfants et Adolescents — Nantes
• HOP Armand-Trousseau — Paris
• Hopital Necker — Paris
• HOP des Enfants — Toulouse

Belgium · 5 centers

• HUB CHU Brugmann — Brussels
• Cliniques Universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Gent — Ghent
• UZ Leuven — Leuven
• CHC Mont Légia — Liège

Canada · 5 centers

• University of Alberta Hospital (University of Alberta) — Edmonton
• BC Children's Hospital — Vancouver
• The Hospital for Sick Children — Toronto
• McGill University Health Centre (MUHC) — Montreal
• Jim Pattison Children's Hospital — Saskatoon

Netherlands · 5 centers

• Amsterdam University Medical Center — Amsterdam
• Universitair Medisch Centrum Groningen — Groningen
• Radboud Universitair Medisch Centrum — Nijmegen
• Erasmus Medisch Centrum — Rotterdam
• UMC Utrecht — Utrecht

Poland · 5 centers

• Uniwersyteckie Centrum Kliniczne — Gdansk
• University Children's Hospital in Lublin — Lublin
• Wojewodzki Szpital Zespolony Im.L.Rydygiera W Toruniu — Torun
• The Children's Memorial Health Institute — Warsaw
• University Clinical Hospital in Wrocław — Wroclaw

Australia · 4 centers

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

Germany · 4 centers

• Universitätsklinikum Köln (AöR) — Cologne
• Universitätsklinikum Hamburg, Eppendorf — Hamburg
• Universitätsklinikum Heidelberg — Heidelberg
• Universitätsklinikum Tübingen — Tübingen

Italy · 4 centers

• Istituto G. Gaslini — Genova
• Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico — Milan
• Azienda Ospedaliera Universitaria di Padova — Padova
• Ospedale Pediatrico Bambino Gesù — Roma

Portugal · 4 centers

• CHUC - Centro Hospitalar e Universitario de Coimbra, EPE — Coimbra
• ULS de São José, E.P.E. - Hospital Dona Estefânia — Lisbon
• ULS de Santa Maria, E.P.E — Lisbon
• CHUP, EPE - Centro Materno Infantil do Norte — Porto

South Korea · 4 centers

Center list to be confirmed — check the primary protocol.

Spain · 4 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

Argentina · 3 centers

• Hospital Italiano de Buenos Aires — CABA
• Hospital de Niños Dr. Ricardo Gutierrez — CABA
• Equipo Ciencia — CABA

Hungary · 3 centers

• Semmelweis University, Faculty of Medicine — Budapest
• University of Debrecen Clinical Centre — Debrecen
• University of Pecs — Pécs

Singapore · 2 centers

• National University Hospital — Singapore
• KK Women's and Children's Hospital — Singapore

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07107945 · 1245-0256 · 2024-512577-27-00 · U1111-1312-1389

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗