A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria

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 (> 79mg/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 ofchildbearing potential (WOCBP) using at least one highly effective birth controlmethod 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 toleratedlabelled daily dose, that has been stable for at least 4 weeks.

Exclusion Criteria:

• Clinically significant, unstable, or uncontrolled medical condition which in theInvestigator's opinion makes it undesirable for the participant to participate inthe study.

• Known hypersensitivity to dapagliflozin or zibotentan or any of the excipients ofthe investigational product. History or ongoing allergy/hypersensitivity, as judgedby 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 therapyduring 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 ortricuspid 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-19during 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´sclinical judgment.

• Malignancy within the past 5 years. Exceptions to this criterion includenon-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 maintenancetherapy.

• Participants treated or expecting to be treated with tolvaptan (including as part ofparticipation in a clinical trial), any other ERAs, or budesonide (where used totreat 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 ofnormal (ULN) or Total serum bilirubin >2 x ULN (an isolated increase in bilirubin inparticipants 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 atrialfibrillation) 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 valveabnormalities

• isolated pulmonary arterial hypertension (as defined by local clinicalpractice) 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 ofthe Investigator, understand and/or comply with the study requirements regardingcontraception.