Clinical trial NCT06835322: Effect of Finerenone in Patients With Non-diabetic Glomerulonephritis
Official title: Effect of Finerenone on Proteinuria and GFR Progression in Patients With Non Diabetic Glomerulonephritis: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glomerulonephritis
Keywords: finerenone
proteinuria
GFR progression
glomerulonephritis
Lead sponsor: Alexandria University
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This research is a prospective randomized multicentric clinical trial in which 100 patients with biopsy proven glomerulonephritis (exception is nephrotic patients with positive anti-PLA2R indicative of primary membranous) will be randomly assigned to one of the study groups using block randomization with a ratio of 1:1.

* Group A: 50 patients with biopsy proven glomerulonephritis who will receive 10 - 20 mg finerenone once daily orally in addition to their regular treatment protocol (RAAS blockers ± immunosuppression) for 6 months.
* Group B: 50 patients with biopsy proven glomerulonephritis who will receive placebo once daily in addition to their regular treatment protocol (RAAS blockers ± immunosuppression) for 6 months.
Primary purpose: TREATMENT

Brief summary: This study aims to assess the effect of finerenone on proteinuria and GFR progression in patients with non-diabetic glomerulonephritis.

Detailed description: In patients with type 2 diabetes and advanced CKD, finerenone resulted in lower risks of CKD progression and cardiovascular events. Mineralocorticoid receptor over activation in the kidney leads to inflammation and fibrosis with subsequent progressive kidney disease. Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, had more potent anti-inflammatory and ant fibrotic effects than steroidal mineralocorticoid receptor antagonists. Finerenone has been shown to reduce the urinary albumin-to-creatinine ratio in patients with CKD treated with an RAS blocker, while having smaller effects on serum potassium levels than spironolactone.

Glomerulonephritis (GN) is an inflammation affecting kidney glomeruli, and is considered an important cause of CKD. Reducing proteinuria is one of the main therapeutic targets in patients with GN.

Eligibility criteria: Inclusion Criteria:

1. GN patients on maximum tolerated doses of an ACEi or ARBs together with their immunosuppression protocol (if needed) for at least 4 weeks.
2. urinary protein excretion \>500 mg/g.
3. Adult patients with age above 18 years.
4. eGFR ≥ 25 mL/ min/1.73 m2.
5. baseline serum potassium level \<5 mEq/L.

Exclusion Criteria:

1. Patients with diabetes mellitus (type 1 or 2).
2. Other non-glomerular kidney diseases.
3. Heart failure.
4. Breast feeding or pregnancy.
5. Patients who received medications to treat hyperkalemia 4 weeks before study.
6. Uncontrolled hypertension (BP \> 160/100).

Primary outcomes:
measure: - Change in kidney function
timeFrame: 6 months
measure: - Change in proteinuria
timeFrame: 6 months
measure: Change in kidney function
timeFrame: 6 months
Secondary outcomes:
measure: - Occurrence of hyperkalemia (potassium level >5 mEq/L)
timeFrame: 6 months
measure: - Need for hospitalization
timeFrame: 6 months
measure: - Serious adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Faculty of Medicine, Aexandria University
Study officials:
affiliation: Associate professor
name: Mohamed Mamdouh Elsayed, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. Epub 2020 Oct 23.
citation: Ruilope LM, Pitt B, Anker SD, Rossing P, Kovesdy CP, Pecoits-Filho R, Pergola P, Joseph A, Lage A, Mentenich N, Scheerer MF, Bakris GL. Kidney outcomes with finerenone: an analysis from the FIGARO-DKD study. Nephrol Dial Transplant. 2023 Feb 13;38(2):372-383. doi: 10.1093/ndt/gfac157.
citation: Barrera-Chimal J, Girerd S, Jaisser F. Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int. 2019 Aug;96(2):302-319. doi: 10.1016/j.kint.2019.02.030. Epub 2019 Mar 13.
citation: Grune J, Beyhoff N, Smeir E, Chudek R, Blumrich A, Ban Z, Brix S, Betz IR, Schupp M, Foryst-Ludwig A, Klopfleisch R, Stawowy P, Houtman R, Kolkhof P, Kintscher U. Selective Mineralocorticoid Receptor Cofactor Modulation as Molecular Basis for Finerenone's Antifibrotic Activity. Hypertension. 2018 Apr;71(4):599-608. doi: 10.1161/HYPERTENSIONAHA.117.10360. Epub 2018 Feb 5.
citation: Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM; Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) Study Group. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA. 2015 Sep 1;314(9):884-94. doi: 10.1001/jama.2015.10081.
citation: Hou JH, Zhu HX, Zhou ML, Le WB, Zeng CH, Liang SS, Xu F, Liang DD, Shao SJ, Liu Y, Liu ZH. Changes in the Spectrum of Kidney Diseases: An Analysis of 40,759 Biopsy-Proven Cases from 2003 to 2014 in China. Kidney Dis (Basel). 2018 Feb;4(1):10-19. doi: 10.1159/000484717. Epub 2017 Dec 8.
citation: AlYousef A, AlSahow A, AlHelal B, Alqallaf A, Abdallah E, Abdellatif M, Nawar H, Elmahalawy R. Glomerulonephritis Histopathological Pattern Change. BMC Nephrol. 2020 May 18;21(1):186. doi: 10.1186/s12882-020-01836-3.