ZODIACZibotentan/Dapagliflozin for Chronic Kidney Disease with High Proteinuria

Study start date: May 7, 2025

Inclusion Criteria: * ≥ 18 years of age at the time of signing the informed consent. * Diagnosis of CKD with eGFR ≥ 20 and \< 90 mL/min/1.73m2 AND UACR \> 700 mg/g (\> 79 mg/mmol) or UPCR \> 1000 mg/g (\> 113 mg/mmol). * Body mass index (BMI) within the range ≤40 kg/m2. * Female participants must be either - not of child-bearing potential or - women of childbearing potential (WOCBP) using at least one highly effective birth control method for at least 3 months prior to first dose of study intervention. * All WOCBP must have a negative serum pregnancy test result at screening. * Receiving RAASi therapy (ACEi or ARB), and for the patient maximum tolerated labelled daily dose, that has been stable for at least 4 weeks. Exclusion Criteria: * Clinically significant, unstable, or uncontrolled medical condition which in the Investigator's opinion makes it undesirable for the participant to participate in the study. * Known hypersensitivity to dapagliflozin or zibotentan or any of the excipients of the investigational product. History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i therapy or ERAs. * NYHA class III or class IV HF. * Participants hospitalised for HF and/or who have not been stable on HF therapy during the last 6 months prior to screening. * HF due to cardiomyopathies that would primarily require other specific treatment. * High output HF (eg, due to hyperthyroidism or Paget's disease). * HF due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement. * Evidence of rales or jugular venous distention on physical examination. * Type 1 diabetes mellitus. * History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal). * Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening. * History of solid organ transplantation or bone marrow transplant. * Any condition with a life expectancy of less than 1 year based on investigator´s clinical judgment. * Malignancy within the past 5 years. Exceptions to this criterion include non-melanoma skin cancer and curatively treated cervical carcinoma in situ. * Significant liver disease as judged by the investigator. * Renal replacement therapy or previous kidney transplant. * Known history of significant drug or alcohol abuse within 12 months of screening. * On treatment with strong or moderate CYP3A4 inducer. * On systemic immunosuppression therapy other than prespecified stable maintenance therapy. * Participants treated or expecting to be treated with tolvaptan (including as part of participation in a clinical trial), any other ERAs, or budesonide (where used to treat IBD or IgAN). * Systolic blood pressure above 160 mmHg and/or below 90 mmHg. * Significant impairment of liver function defined as AST or ALT \>3 x upper limit of normal (ULN) or Total serum bilirubin \>2 x ULN (an isolated increase in bilirubin in participants with known Gilbert's syndrome is not a reason for exclusion). * NT-proBNP ≥ 600 pg/mL (or NT-proBNP ≥ 1200 pg/mL, if associated with atrial fibrillation) measured by local laboratory at screening. * Any of the following results of echocardiography at screening: * left ventricular ejection fraction (LVEF) \< 50% * significant ventricular wall motion abnormality or severe cardiac valve abnormalities * isolated pulmonary arterial hypertension (as defined by local clinical practice) or right ventricular failure; in the absence of left-sided HF * Women who are pregnant, breast-feeding, or women with intent of getting pregnant. * Women who are not willing to use adequate contraception or cannot, in the opinion of the Investigator, understand and/or comply with the study requirements regarding contraception.