| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Chronic kidney disease
Proteinuria
|
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Participants must be 6 months to <18 years at the time when the informed consent/assent is signed
2. Participants must have a clinical diagnosis of CKD at screening which is defined as
a. CKD stages I-III (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. UPCR of ≥ 0.50 g/g in participants ≥ 2 years with CKD stage II and III or
ii. UPCR ≥ 1.0 g/g for patients < 2 years of age or ≥ 2 years of age and with CKD stage I
3. Participants must have stable kidney function defined as no change in eGFR ≥± 15% for children ≥1 year to <18 years of age, or no change in serum creatinine ≥ ±0.10 mg/dL for infants 6 months to <1 year of age
between screening and D0
4. Treated with an ACEI or 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
6. Participants can be enrolled in the outpatient or inpatient setting
7. Study participants must have a body weight ≥4kg
8. Pregnancy testing as well as highly effective female contraception as appropriate for sexual maturity and activity and as required by local regulations are required for female participants
9. Participant has understood the study and if applicable, has signed an informed assent. The parent(s) or guardian(s) is capable of giving signed informed consent as described which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol
10. Participant is able to receive enteral feeding (solid food, bottle or cup fed, feeding through nasogastric or gastric feeding tubes) with or without breastfeeding
11. A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow up; accompany the participant to the study site on each assessment day (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant; accurately and reliably dispense study intervention as directed.
12. A legal guardian or primary caregiver must be able to accurately maintain the child's take-home record, including items of general health. |
|
| E.4 | Principal exclusion criteria |
1. Planned urological surgery expected to influence renal function
2. Children with hemolytic uremic syndrome diagnosed ≤6 months prior to screening
3. Patients with nephrotic syndrome receiving albumin infusions within the last 6 months prior to screening
4. Scheduled renal transplant within the next 6 months
5. Renal allograft in place
6. Bilateral renal artery stenosis
7. Acute kidney injury requiring dialysis within 6 months prior to screening
8. Patients with genetically defined primary tubulopathies leading to tubular proteinuria, such as Dent´s disease
9. Systemic hypertension stage 2 in children ≥1 year of age defined according to institutional guidelines on blood pressure management at screening or randomization
10. SBP above 110 mmHg in infants 6 months to <1 year of age at screening or randomization
11. 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).
12. Known hypersensitivity to the study treatment (active substance orexcipients)
13. Addison's disease
14. Severe hepatic insufficiency defined by e.g. Child-Pugh C or analogous scores
15. Participants using rituximab, cyclophosphamide, abatacept, or intravenous glucocorticoids, within <6 months prior to screening for any reason
16. Concomitant therapy with an MRA (eplerenone, spironolactone, esaxerenone, canrenone), any renin inhibitor (aliskiren, enalkiren, remikiren), any SGLT2 inhibitor (SGLT2i), sacubitril/valsartan combination (ARNI), or potassium-sparing diuretic (amiloride, triamterene) which cannot be discontinued at least 30 days prior to the screening visit
17. Concomitant therapy with both ACEI and ARBs in case one of those cannot be discontinued at least 30 days prior to the screening visit
18. Concomitant therapy with potent CYP3A4 inhibitors, moderate or potent CYP3A4 inducers and/or the moderate CYP3A4 inhibitor erythromycin (to be stopped at least 7 days before randomization)
19. Previous assignment to treatment during this study
20. Simultaneous participation in another interventional clinical study (e.g., Phase 1-3 clinical studies) or treatment with any investigational medicinal product within 30 days prior to Run-in visit
21. Any other condition or therapy, which would make the participant unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 6 months)
22. Any other history, condition, therapy, or uncontrolled intercurrent illness which could in the opinion of the investigator affect compliance with study requirements
23. Pregnant or breast-feeding or intention to become pregnant during the study
24. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the
investigational site) |
|
| 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) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From baseline to day 180±7 |
|
| 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, AUCĪ,md) based on total concentrations in plasma
6. Taste and texture of the pediatric formulation |
|
| 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 |
|
| 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 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
| Australia |
| Canada |
| Israel |
| Korea, Republic of |
| Turkey |
| United States |
| United Kingdom |
| Switzerland |
|
| 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
|
| The end of the study is defined as the date of the last visit of the last participant in the study globally |
|
| E.8.9 Initial estimate of the duration of the trial |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 16 |
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