A Biomarker-targeted Clinical Trial to Optimize Treatment for Patients With Chronic Kidney Disease

The study is a prospective, randomized, open-label, parallel-group, multicenter study. CKD-bioMatch will enroll 125 individuals with CKD (eGFR ≥ 25 mL/min/1.73m² and UACR 100-5000 mg/g). Participants will be randomized 1:1 to a biomarker-targeted treatment approach versus standard of care.

In the treatment arm, a sequence of pharmacological treatments will be added (dapagliflozin, finerenone, and/or semaglutide), guided by the participant's characteristics and the urinary biomarkers urinary albumin-to-creatinine ratio (UACR) and urinary epidermal growth factor (UEGF). Participants will start treatment with one of the three study medications. After approximately four weeks on the maximum tolerated dose of the allocated medication, UACR and UEGF will be measured, and based on the biomarker response, a decision will be made to continue, switch, or add a new treatment. If a second drug is initiated, the treatment effect of that second drug will be evaluated on UACR and UEGF after four weeks on the maximum tolerated dose, and if the UACR response is insufficient, a third drug can be added, or the third drug can replace the second drug. The biomarker response of the third drug will be evaluated in the same manner as that of the first two drugs.

Inclusion criteria

• Age ≥ 18 and ≤ 75 years
• UACR 100-5000 mg/g (11.3-565 mg/mmol) in two consecutive first-morning void urine samples at screening. (UACR 80-100 mg/g is accepted if historical measurements are above 100 mg/g and if it cannot be explained by any new treatment.)
• Stable treatment with a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least four weeks prior to randomization. (Unless such treatment is contraindicated or not tolerated.)
• Ability to communicate with the study staff and understand and sign the informed consent.

Exclusion criteria

• eGFR < 25 mL/min/1.73m2 at screening.
• Treatment with two or all three of the study drugs
• History of pancreatitis at screening
• Body mass index < 18.5 kg/m2 at screening
• Type 1 diabetes
• Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrollment
• NYHA class IV Congestive Heart Failure at screening
• Potassium > 5.0 mmol/L at screening
• Addison's Disease
• Concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, cobicistat, clarithromycin)
• Treatment with a potassium-sparing diuretic or a mineralocorticoid receptor antagonist, except for finerenone (e.g., spironolactone, eplerenone, or amiloride)
• Elevated Alanine Aminotransferase (ALT) > 3 x upper normal limit at screening, autoimmune hepatitis, and/or severe hepatic impairment (including but not limited to a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt).
• Autosomal dominant or autosomal recessive polycystic kidney disease
• Lupus nephritis or ANCA-associated vasculitis, or any other primary or secondary kidney disease requiring immunosuppressive therapy within 6 months prior to screening
• Kidney transplant or dialysis
• Known or suspected hypersensitivity to the study medications or related products
• Presence or history of malignant neoplasms (except basal cell skin cancer or squamous cell skin cancer) within five years before screening.
• Any other history, condition, therapy, or uncontrolled intercurrent illness that could, as judged by the investigator, affect participant safety or compliance with study requirements.
• A female who is pregnant, breastfeeding, or intends to become pregnant, or a woman of childbearing potential (WOCBP) who is not using highly effective contraceptive methods.
• Known or suspected abuse of narcotics.
• Participant in another intervention study.
• Vulnerable (i.e., under guardianship) or mentally incapacitated subjects (i.e., not able to understand and sign the informed consent).