Status:
RECRUITING
A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria
Lead Sponsor:
AstraZeneca
Conditions:
Chronic Kidney Disease With High Proteinuria
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants with Chronic Kidney Disease and High Proteinuria (ZODIAC)
Detailed Description
This is a Phase II, multicentre, randomised, double-blind, active-controlled, 2-arm parallel group study to evaluate the efficacy, safety, and tolerability of zibotentan and dapagliflozin in FDC compa...
Eligibility Criteria
Inclusion
- ≥ 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
- 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.
Key Trial Info
Start Date :
May 7 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 31 2026
Estimated Enrollment :
224 Patients enrolled
Trial Details
Trial ID
NCT06942910
Start Date
May 7 2025
End Date
July 31 2026
Last Update
October 29 2025
Active Locations (10)
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1
Research Site
Aramil, Russia, 624002
2
Research Site
Izhevsk, Russia, 426061
3
Research Site
Moscow, Russia, 111539
4
Research Site
Moscow, Russia, 117036