Rationale and design of a randomised phase III registration trial investigating finerenone in participants with type 1 diabetes and chronic kidney disease: The FINE-ONE trial

Hiddo J L Heerspink; Andreas L Birkenfeld; David Z I Cherney; Helen M Colhoun; Linong Ji; Chantal Mathieu; Per-Henrik Groop; Richard E Pratley; Sylvia E Rosas; Peter Rossing; Jay S Skyler; Katherine R Tuttle; Robert Lawatscheck; Charlie Scott; Robert Edfors; Markus F Scheerer; Peter Kolkhof; Janet B McGill

doi:10.1016/j.diabres.2023.110908

Rationale and design of a randomised phase III registration trial investigating finerenone in participants with type 1 diabetes and chronic kidney disease: The FINE-ONE trial

Diabetes Res Clin Pract. 2023 Oct:204:110908. doi: 10.1016/j.diabres.2023.110908. Epub 2023 Oct 5.

Authors

Hiddo J L Heerspink¹, Andreas L Birkenfeld², David Z I Cherney³, Helen M Colhoun⁴, Linong Ji⁵, Chantal Mathieu⁶, Per-Henrik Groop⁷, Richard E Pratley⁸, Sylvia E Rosas⁹, Peter Rossing¹⁰, Jay S Skyler¹¹, Katherine R Tuttle¹², Robert Lawatscheck¹³, Charlie Scott¹⁴, Robert Edfors¹⁵, Markus F Scheerer¹⁶, Peter Kolkhof¹⁷, Janet B McGill¹⁸

Affiliations

¹ Clinical Pharmacy and Pharmacology, University of Groningen University Medical Centre Groningen, PO Box 30.001, 9700 RB Groningen, Netherlands. Electronic address: h.j.lambers.heerspink@umcg.nl.
² Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Otfried Müller Street 47, 72076 Tübingen, Germany; German Centre for Diabetes Research (DZD), Neuherberg, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany.
³ Division of Nephrology, University Health Network, Toronto General Hospital, University of Toronto, 585 University Ave, 8N-845, Toronto, Ontario M5G 2N2, Canada.
⁴ Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
⁵ Departments of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Centre, No 11, Xizhimen South Street, Beijing 100044, China.
⁶ Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
⁷ Department of Nephrology, University of Helsinki and Helsinki University Hospital, Biomedicum Helsinki (C318b), Haartmaninkatu 8, FIN-00290 Helsinki, Finland.
⁸ AdventHealth Translational Research Institute, Orlando, FL 32804, USA.
⁹ Kidney and Hypertension Unit, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
¹⁰ Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, 2730 Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
¹¹ Department of Medicine, University of Miami, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
¹² Providence Inland Northwest Health, University of Washington School of Medicine, 105 W. 8th Avenue, Suite 250 E, Spokane, WA 99204, USA.
¹³ Cardiology and Nephrology Clinical Research, Bayer AG, Research & Development, Pharmaceuticals, Clinical Development, Building S101, 13342 Berlin, Germany.
¹⁴ Data Science and Analytics, Bayer PLC, Research & Development, Pharmaceuticals, 400 South Oak Way, Reading RG2 6AD, UK.
¹⁵ Cardiovascular Studies & Pipeline, Medical Affairs & Pharmacovigilance, Pharmaceuticals, Bayer AG, Building S102, 13342 Berlin, Germany.
¹⁶ Medical Affairs & Pharmacovigilance, Pharmaceuticals, TA CardioRenal & Heart Disease, Bayer AG, Building S102, 04/160, 13353 Berlin, Germany.
¹⁷ Research and Development, Pharmaceuticals, Cardiovascular Precision Medicines, Bayer AG, 42113 Wuppertal, Germany.
¹⁸ Division of Endocrinology, Metabolism & Lipid Research, Washington University in St. Louis, School of Medicine, 660 S. Euclid, Campus Box 8127, St. Louis, MO 63110, USA.

PMID: 37805000
DOI: 10.1016/j.diabres.2023.110908

Abstract

Aims: Despite guideline-recommended treatments, including renin angiotensin system inhibition, up to 40 % of individuals with type 1 diabetes develop chronic kidney disease (CKD) putting them at risk of kidney failure. Finerenone is approved to reduce the risk of kidney failure in individuals with type 2 diabetes. We postulate that finerenone will demonstrate benefits on kidney outcomes in people with type 1 diabetes.

Methods: FINE-ONE (NCT05901831) is a randomised, placebo-controlled, double-blind phase III trial of 7.5 months' duration in ∼220 adults with type 1 diabetes, urine albumin/creatinine ratio (UACR) of ≥ 200-< 5000 mg/g (≥ 22.6-< 565 mg/mmol) and eGFR of ≥ 25-< 90 ml/min/1.73 m².

Results: The primary endpoint is relative change in UACR from baseline over 6 months. UACR is used as a bridging biomarker (BB), since the treatment effect of finerenone on UACR was associated with its efficacy on kidney outcomes in the type 2 diabetes trials. Based on regulatory authority feedback, UACR can be used as a BB for kidney outcomes to support registration of finerenone in type 1 diabetes, provided necessary criteria are met. Secondary outcomes include incidences of treatment-emergent adverse events, treatment-emergent serious adverse events and hyperkalaemia.

Conclusions: FINE-ONE will evaluate the efficacy and safety of finerenone in type 1 diabetes and CKD. Finerenone could become the first registered treatment for CKD associated with type 1 diabetes in almost 30 years.

Trial registration: ClinicalTrials.gov NCT05901831.

Keywords: Albuminuria; Chronic kidney disease; Finerenone; Type 1 diabetes.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase III

MeSH terms

Adult
Biomarkers
Diabetes Mellitus, Type 1* / complications
Diabetes Mellitus, Type 1* / drug therapy
Diabetes Mellitus, Type 2* / complications
Diabetic Nephropathies* / etiology
Double-Blind Method
Glomerular Filtration Rate
Humans
Renal Insufficiency* / complications
Renal Insufficiency, Chronic* / complications
Renal Insufficiency, Chronic* / drug therapy

Substances

finerenone
Biomarkers

Associated data

ClinicalTrials.gov/NCT05901831