A study to learn how well 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 by children with chronic kidney disease and proteinuria in addition to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

4 Feb 2022 → ongoing

Decision date (initial)

2024-04-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-504884-17-00

EudraCT number

2021-002071-19

ClinicalTrials.gov

NCT05196035

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Therapy, Pharmacokinetic

The primary objective is to demonstrate that finerenone in addition to an ACEI or ARB is superior to placebo in reducing urine protein excretion

Secondary objectives 4

1. To assess the safety profile of finerenone in addition to SoC in pediatric CKD patients compared to placebo
2. To further support the efficacy of finerenone in addition to SoC compared to placebo
3. To confirm the dose and systemic exposure of finerenone in CKD patients
4. To assess the acceptability and palatability of the age-appropriate pediatric formulation

Conditions and MedDRA coding

Proteinuria

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001623-PIP01-14

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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. For participants with a creatinine of > 0.8 mg/dL at screening: no increase or decrease in eGFR by ≥ 20% at D0 b. For participants with a creatinine of ≤ 0.8 mg/dL at screening: no increase or decrease in creatinine ≥ 0.15 mg/dL at D0.
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

Exclusion criteria 11

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 (low-dose glucocorticoids or a short course of glucocorticoids for, e.g., treatment of an asthma exacerbation are allowed)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean reduction from baseline to Month 6 in Urinary Protein-toCreatinine Ratio (Percent change from baseline to day 180±7 in UPCR)

Secondary endpoints 6

1. Number of participants with a. AEs b. Serious TEAEs c. TEAEs and serious TEAEs leading to discontinuation of treatment d. Study drug related TEAEs and serious TEAEs e. TEAEs categorized by severity f. TEAEs by maximum intensity g. No. of participants hospitalized with hyperkalemia h. No. of participants discontinuing due to hyperkalemia i. No. of participants hospitalization for worsening of renal function j. No. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer AG

Sponsor organisation

Bayer AG

Address

Kaiser-Wilhelm-Allee 1, Wiesdorf Wiesdorf

City

Leverkusen

Postcode

51373

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 12

Locations

17 EU/EEA countries · 67 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 486 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications