E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease Proteinuria |
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E.1.1.1 | Medical condition in easily understood language |
Chronic kidney disease, which is long-term kidney disease, and proteinuria, a condition in which a person has extra protein in the urine |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037032 |
E.1.2 | Term | Proteinuria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate that finerenone in addition to an ACEI or ARB is superior to placebo in reducing urine protein excretion |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: To assess the safety profile of finerenone in addition to SoC in pediatric CKD patients compared to placebo To further support the efficacy of finerenone in addition to SoC compared to placebo To confirm the dose and systemic exposure of finerenone in CKD patients To assess the acceptability and palatability of the age-appropriate pediatric formulation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants must be 6 months to <18 years old at the time when the informed consent/assent is signed 2. Participants must have a clinical diagnosis of chronic kidney disease (CKD) at screening which is defined as a. CKD stages 1-3 (eGFR ≥30 mL/min/1.73m^2) for children ≥1 year to <18 years of age or b. a serum creatinine ≤ 0.40 mg/dL for infants 6 months to < 1 year of age and c. severely increased proteinuria as defined by i. Urinary protein-to-creatinine ratio (UPCR) of ≥ 0.50 g/g in participants ≥ 2 years with CKD stage 2 and 3 or ii. UPCR ≥ 1.0 g/g for patients < 2 years of age or ≥ 2 years of age and with CKD stage 1 3. Participants must have stable kidney function between screening and D0 defined as: a. no increase or decrease in eGFR ≥ 15% for children ≥1 year or b. no increase or decrease in creatinine ≥ 0.10 mg/dL for children <1 year 4. 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 5. 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 |
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E.4 | Principal exclusion criteria |
1. Planned urological surgery expected to influence renal function 2. Children with hemolytic uremic syndrome (HUS) diagnosed ≤6 months prior to screening 3. Patients with nephrotic syndrome receiving albumin infusions within the last 6 months prior to screening 4. Patients who are candidates for renal transplantation, i.e., a kidney transplantation scheduled within the study time frame 5. Renal allograft in place 6. Bilateral renal artery stenosis 7. Acute kidney injury requiring dialysis within 6 months prior to screening 8. Systemic hypertension stage 2 in children ≥1 year of age defined according to guidelines on blood pressure management at screening or randomization 9. Systolic blood pressure (SBP) above 110 mmHg in infants 6 months to <1 year of age at screening or randomization 10. 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) 11. Participants with immune-mediated CKD using rituximab, cyclophosphamide, abatacept, or high-dose glucocorticoids (e.g., prednisolone ≥0.5 mg/kg/d), within <6 months prior to screening (lowdose glucocorticoids or a short course of glucocorticoids for, e.g., treatment of an asthma exacerbation are allowed) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean reduction from baseline to Month 6 in Urinary Protein-to-Creatinine Ratio (Percent change from baseline to day 180±7 in UPCR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to day 180±7 |
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E.5.2 | Secondary end point(s) |
1. Number of participants with a. Adverse Events (AEs) b. Serious Treatment Emergent Adverse Events (TEAEs) c. TEAEs and serious TEAEs leading to discontinuation of treatment d. Study drug related TEAEs and serious TEAEs e. TEAEs categorized by severity (mild, moderate, severe) f. TEAEs by maximum intensity g. Number of participants hospitalized with hyperkalemia h. Number of participants discontinuing due to hyperkalemia i. Number of participants hospitalization for worsening of renal function j. Number of participants discontinuing due to worsening of renal function 2. Change in serum potassium levels, serum creatinine, eGFR and systolic blood pressure from baseline to day 180±7 3. Urinary Protein-to-Creatinine Ratio (UPCR) reduction of at least 30% from baseline to day 180±7 (Proportion of responders at the day 180±7 time point, where a responder is defined as a >=30% reduction in UPCR compared to baseline 4. Change in UACR from baseline to day 180±7 5. PK (finerenone Cmax,md, AUCτ,md) based on total concentrations in plasma 6. Taste and texture of the pediatric formulation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From the start of study intervention to last follow-up visit (last study intervention + 3 days) 2. From baseline to day 180±7 3. From baseline to day 180±7 4. From baseline to day 180±7 5. From baseline to day 180±7 6. From baseline to day 180±7 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Switzerland |
Australia |
Austria |
Belgium |
Canada |
Czechia |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Korea, Republic of |
Lithuania |
Netherlands |
Poland |
Portugal |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last visit of the last participant in the study globally |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 11 |