Effect of Treatment with Finerenone on Cardio-Renal Target Organ Damage in Patients with Type 2 Diabetes – A Randomized Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aarhus University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Eye Diseases [C11], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

15 Oct 2024 → ongoing

Decision date (initial)

2024-09-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Aarhus University · The Augustinus Foundation · Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond · Simon Spies Foundation · Steno Diabetes Center Aarhus · Karl G. Andersens Fond

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis

To examine the effect of combination therapy with finerenone and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our hypothesis is that the combination therapy will be either synergetic or additive on various cardio-renal endpoints.

Conditions and MedDRA coding

Type 2 diabetes, chronic kidney disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of type 2 diabetes according to the World Health Organization definition
2. Chronic kidney disease defined as eGFR ≥ 25 ml/min/1.73 m2 and elevated albuminuria (urinary albumin-to-creatine ratio of 30-5000 mg/g).
3. Current treatment with an sodium-glucose-cotransporter 2 (SGLT2)-inhibitor at maximally tolerated dose
4. Current treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) at maximally tolerated dose
5. Serum potassium level of 4.8 mmol/L or less at the time of screening
6. Age above 18 years
7. Speak and understand Danish fluently

Exclusion criteria 17

1. Inability to give informed consent
2. Poorly controlled medical condition, e.g. congestive heart failure (New York Heart Association III-IV or EF ≤ 40%), recent (within 3 months) stroke or acute myocardial infarction or any other condition that in the opinion of the investigator will put the trial participant at risk if participating in the trial.
3. Allergy to finerenone or any of the excipients contained in the drug.
4. Current systemic treatment with strong inhibitors of CYP3A4 (e.g. itraconazol, ketocona-zole, ritonavir, cobicistat, clarithromycin) or strong inducers of CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital).
5. Current treatment with other mineralocorticoid receptor antagonists (e.g. spironolactone, eplerenone etc.).
6. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
7. Addison’s disease.
8. Contraindications to magnetic resonance imaging (MRI).
9. Severe renal disease with eGFR<25 ml/min/1.73m2
10. Severe hepatic disease (serum ALAT above 3x upper limit of normal)
11. Active cancer diagnosis other than basal cell carcinoma
12. Treatment with systemic steroids at time of randomization.
13. Bariatric surgery within 2 years or other gastrointestinal surgeries that induce chronic malabsorption.
14. Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake.
15. Chronic or acute pancreatitis.
16. Pregnancy or breastfeeding
17. Previous renal or heart transplantation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in left ventricular mass measured by non-contrast cardiac MRI.
2. Change in albuminuria measured by urinary albumin-to-creatinine ratio (UACR) in morning spot urine samples (first morning voids).

Secondary endpoints 16

1. Change in the rate of myocardial fibrosis (extracellular cardiac volume – ECV %) measured by MRI of the heart using gadolinium-containing contrast.
2. Change in the rate of myocardial fibrosis measured by non-contrast T1-mapping, measured by non-contrast MRI of the heart.
3. Change in left ventricular ejection fraction (EF), left ventricular and atrial volumes measured by non-contrast MRI of the heart.
4. Change in the rate of pulse wave velocity in the aorta measured by non-contrast MRI of the heart.
5. Change in arterial stiffness assessed as carotid-femoral pulse wave velocity.
6. Change in 24-hour blood pressure.
7. Change in inflammatory and fibrotic biomarkers related to cardiovascular disease measured in blood and urine.
8. Change in measured glomerular filtration rate (mGFR) assessed by injection of a tracer.
9. Change in eGFR slope including all available outpatient eGFR measured a) from before treatment to last day of treatment b) from 4 weeks after treatment initiation to last day after treatment.
10. Change in UACR by repeated measures analysis including all available outpatient UACR measurements from before treatment to the last day after treatment.
11. Change in markers of the renin-angiotensin-aldosterone system measured in blood and urine.
12. Change in inflammatory and fibrotic biomarkers related to chronic kidney disease (e.g. markers of renal tubule damage) measured in blood and urine.
13. Change in kidney microstructure and fibrosis assessed as changes in T1-mapping and changes in the rate of apparent diffusion coefficient (ADC)-values of diffusion-weighted MRI of the kidneys using non-contrast MRI.
14. Change in renal oxygenation assessed by BOLD MRI and change in renal perfusion with a pseudo continuous arterial spin labeling (pCASL), both non-contrast MR techniques.
15. Change in kidney size measured by a Dixon water/fat sequence MRI, a non-contrast MRI technique.
16. Change in thoracic aortic wall volume (TWV) measured by MRI of the heart.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aarhus University Hospital

Sponsor organisation

Aarhus University Hospital

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus University Hospital

Contact name

Esben Laugesen

Public contact point

Organisation

Aarhus University Hospital

Contact name

Esben Laugesen

Third parties 1

Locations

1 EU/EEA country · 1 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 16 files

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

Application history

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