A study to learn how well the treatment combination of finerenone and empagliflozin works and how safe it is compared to each treatment alone in adult participants with long-term kidney disease (chronic kidney disease) and type 2 diabetes.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

25 May 2022 → 14 Mar 2025

Decision date (initial)

2024-05-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bayer AG

External identifiers

EU CT number

2023-506981-30-00

EudraCT number

2021-003037-11

ClinicalTrials.gov

NCT05254002

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Therapy

To demonstrate that combination therapy using finerenone and empagliflozin is superior in reducing UACR (Urinary albumin to-creatinine ratio) than either empagliflozin or finerenone alone.

Secondary objectives 2

1. To further investigate the efficacy of combination therapy using finerenone and empagliflozin versus either finerenone or empagliflozin alone
2. To evaluate the safety of combination therapy using finerenone and empagliflozin versus either finerenone or empagliflozin alone

Conditions and MedDRA coding

Chronic kidney disease in type 2 diabetes mellitus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Participant with a clinical diagnosis of chronic kidney disease (CKD) and the following: a. In Part A: eGFR 40-90 ml/min/1.73m^2 (with no more than 20% having an eGFR >75 ml/min/1.73m^2) using Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula at screening visit and at least one historical value of eGFR <60 mL/min/1.73 m^2 within 3 months or have a registered diagnosis of CKD. b. In Part B: eGFR 30-90 ml/min/1.73m^2 (with no more than 20% having an eGFR >75 ml/min/1.73m^2) using CKD-EPI formula at screening visit and at least one historical value of eGFR <60 mL/min/1.73 m^2 within 3 months or have a registered diagnostic of CKD. c. 100 ≤UACR <5000 mg/g at screening visit (mean value from 3 morning void samples) and documentation of albuminuria/proteinuria (quantitative or semi-quantitative measurement) in the participant's medical records at least 3 months prior to screening
2. Participant with type 2 diabetes (T2D) as defined by the American Diabetes Association (ADA 2021), with glycated hemoglobin (HbA1c) at screening <11%.
3. Participant treated with the clinically maximum tolerated dose, as per investigator judgment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), but not both, for more than 1 month at screening visit.

Exclusion criteria 7

1. Participants with type 1 diabetes (T1D).
2. Participant with hepatic insufficiency classified as Child-Pugh C.
3. Participant with blood pressure at Day 1 visit (Visit 2) higher than 160 SBP or 100 DBP or SBP lower than 90 mmHg.
4. Participant currently treated with a sodium/glucose cotransporter-2 inhibitor (SGLT2i) or SGLT-1/2i or who received a SGLT2i or SGLT-1/2i which cannot be discontinued at least 8 weeks prior to the screening visit and during study intervention treatment.
5. Participant treated with another mineralocorticoid receptor antagonist (MRA) (e.g., eplerenone, esaxerenone, spironolactone, canrenone), a renin inhibitor, potassium supplements, a potassium sparing diuretic (e.g., amiloride, triamterene), a potassium binder agent, or angiotensin receptor-neprilysin inhibitor (ARNI) which cannot be discontinued at least 8 weeks prior to the screening visit and during study intervention treatment.
6. Participants currently treated or who were treated with Finerenone (Kerendia©) within 8 weeks prior to the screening visit.
7. Participant with serum/plasma potassium (K+) above 4.8 mmol/L at screening (central laboratory value).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Mean ratio of change from baseline to Day 180 in Urinary albumin to creatinine ratio (UACR) for the combination therapy group, to empagliflozin alone.
2. Mean ratio of change from baseline to Day 180 in UACR for the combination therapy group, to finerenone alone.

Secondary endpoints 23

1. Relative change in UACR between end of treatment visit and 30 days after end of treatment visit.
2. Relative change in UACR between 30 days after end of treatment visit and baseline.
3. Relative change in UACR category (>30%, >40%, >50%) at 180 days.
4. Ratio of change from baseline in eGFR at 30 days.
5. eGFR decline greater than 30% at 30 days from baseline.
6. Ratio of change in eGFR at 180 days and 210 days from day 30.
7. Proportion of participants with of AKI events.
8. Total number of AKI events.
9. Number of participants with hyperkalemia events (moderate hyperkalemia [5.5 6.0 mmol/L])
10. Total number of hyperkalemia events (moderate hyperkalemia [5.5 6.0 mmol/L])
11. Change from baseline in K+
12. Proportion of participants with severe hypoglycemia events.
13. Total number of events of severe hypoglycemia events.
14. Proportion of participants with symptomatic hypotension events.
15. Total number of symptomatic hypotension events.
16. Proportion of participants with genital mycotic events.
17. Total number of genital mycotic events.
18. Proportion of participants with ketoacidosis events.
19. Total number of ketoacidosis events.
20. Proportion of participants with necrotizing fasciitis of the perineum events.
21. Total number of necrotizing fasciitis of the perineum events.
22. Proportion of participants with urosepsis and pyelonephritis events.
23. Total number of urosepsis and pyelonephritis events.

Investigational products

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

Test 3

Placebo 2

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 6

Locations

7 EU/EEA countries · 57 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 85 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