CKD-bioMatch: A biomarker-targeted clinical trial to optimize treatment for patients with chronic kidney disease

Prior treatment

• Concomitant treatment with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, cobicistat, clarithromycin)
• 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
• Treatment with two or all of the three study drugs
• Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrolment

Other illness

• Autosomal dominant or autosomal recessive polycystic kidney disease
• 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.
• History of pancreatitis at screening
• Type 1 diabetes
• NYHA class IV Congestive Heart Failure at screening
• Addison’s Disease

Lab values

• eGFR < 25 mL/min/1.73m2 at screening (FOR ITALY ONLY: eGFR < 30 and eGFR > 60 mL/min/1.73m2 at screening.)
• 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.)
• Serum potassium > 5.0 mmol/L at screening

Other

• A female who is pregnant, breastfeeding, or intends to become pregnant, or women of childbearing potential (WOCBP) who are 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).
• Body mass index < 18.5 kg/m2 at screening

• Age ≥ 18 and ≤ 75 years
• UACR 100-5000 mg/g (11.3-565 mg/mmol) in two consecutive first-morning void urine samples. (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 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.