Chronic Kidney Disease With High ProteinuriaPhase 2ZODIACNCT06942910
A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria
A Phase 2 study testing Zibotentan/Dapagliflozin and Dapagliflozin in people with Chronic Kidney Disease With High Proteinuria, run by AstraZeneca at 14 sites in Russia.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease With High Proteinuria
- What is being tested?
- Zibotentan/Dapagliflozin and Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 14 sitesRussia
- Study dates
- 7 May 2025to 26 Sep 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Russia14 sites
Research Site
Aramil, 624002
Research Site
Izhevsk, 426061
Research Site
Krasnoyarsk, 660062
Research Site
Moscow, 111539
Research Site
Moscow, 117036
Research Site
Moscow, 129327
Research Site
Omsk, 644112
Research Site
Orenburg, 460018
Research Site
Perm, 614000
Research Site
Saint Petersburg, 195067
Research Site
Saratov, 410053
Research Site
Saratov, 410054
Research Site
Ulyanovsk, 432009
Research Site
Yaroslavl, 150062
About this study
Official title: A Multicentre, Randomised, Double-blind, Active-Controlled, 2-arm Parallel-group Treatment, Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria
A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants with Chronic Kidney Disease and High Proteinuria
Read the 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 compared to dapagliflozin alone, given QD on top of SoC, in adult participants with CKD and high proteinuria, with or without T2DM.
Participants who are not already on SGLT2i at screening will receive a 28 day run in intervention with SGLT2i (dapagliflozin) QD. All participants will undergo a 12-week double-blind period. At the end of the treatment visit, participants will discontinue the blinded study intervention and begin open-label dapagliflozin monotherapy until the conclusion of the 4-week safety follow-up period.
The results of this study will provide clinical data on efficacy and safety of an innovation treatment in the new region (the Russian Federation), which will be an important additional data source for Zibotentan/Dapagliflozin FDC approval process in the Eurasian Economic Union.
- Being tested
- Zibotentan/Dapagliflozin, Dapagliflozin
- Keywords
- Zibotentan, Nephrology, Dapagliflozin, Sodium-glucose co-transporter 2, sodium-glucose co-transporter 2 inhibitor, Kidney diseases, Endothelin antagonist, High Proteinuria
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zibotentan/DapagliflozinDrug
Participants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to
DapagliflozinDrug
Participants will receive monotherapy dapagliflozin as per the arms they are randomized to
| Study group | Role | What they receive |
|---|---|---|
| Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B | Experimental | Drug dose is determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination. Receives: Drug: Zibotentan/Dapagliflozin |
| Dapagliflozin alone | Active comparator | Participants will receive daily oral dose of dapagliflozin. Receives: Drug: Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in log-transformed Urinary Albumin to Creatinine Ratio (UACR) from baseline
To estimate the efficacy of zibotentan and dapagliflozin in FDC versus dapagliflozin alone in reducing albuminuria
Measured: At Week 12
Secondary outcomes (3)
Change in log-transformed Urinary Protein to Creatinine Ratio (UPCR) from baseline
To estimate the efficacy of zibotentan and dapagliflozin in FDC versus dapagliflozin alone in reducing proteinuria
Measured: At Week 12
Change in systolic and diastolic blood pressure (BP) from baseline
To estimate the efficacy of zibotentan and dapagliflozin in FDC versus dapagliflozin alone in reducing systolic and diastolic BP
Measured: At Week 12
Number of participants experiencing adverse events
To assess the safety and tolerability of treatment with zibotentan and dapagliflozin in FDC compared to dapagliflozin alone during 12 weeks of treatment and 4 weeks of safety follow-up
Measured: From Week 1 (Day 1) until Follow-up visit (Week 18, Day 112)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start7 May 2025
- Primary completion26 Sep 2026 (estimated)
- Study completion26 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney Disease With High ProteinuriaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06942910
- Sponsor's protocol ID
- AZ-RU-00010
- Acronym
- ZODIAC
- Status last verified
- Aug 2026
- First submitted
- 17 Apr 2025
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomised, Double-blind, Active-Controlled, 2-arm Parallel-group Treatment, Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin Alone in Adult Participants With Chronic Kidney Disease and High Proteinuria
- ClinicalTrials.gov ID
- NCT06942910
- Acronym / sponsor ID
- ZODIAC / AZ-RU-00010
- Keywords
- Zibotentan, Nephrology, Dapagliflozin, Sodium-glucose co-transporter 2, sodium-glucose co-transporter 2 inhibitor, Kidney diseases, Endothelin antagonist, High Proteinuria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 224 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 7 May 2025 (actual)
- Primary completion
- 26 Sep 2026 (estimated)
- Study completion
- 26 Sep 2026 (estimated)
- First posted
- 24 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants with Chronic Kidney Disease and High Proteinuria
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 compared to dapagliflozin alone, given QD on top of SoC, in adult participants with CKD and high proteinuria, with or without T2DM.
Participants who are not already on SGLT2i at screening will receive a 28 day run in intervention with SGLT2i (dapagliflozin) QD. All participants will undergo a 12-week double-blind period. At the end of the treatment visit, participants will discontinue the blinded study intervention and begin open-label dapagliflozin monotherapy until the conclusion of the 4-week safety follow-up period.
The results of this study will provide clinical data on efficacy and safety of an innovation treatment in the new region (the Russian Federation), which will be an important additional data source for Zibotentan/Dapagliflozin FDC approval process in the Eurasian Economic Union.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B | Experimental | Drug: Zibotentan/DapagliflozinDrug dose is determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination. |
| Dapagliflozin alone | Active comparator | Drug: DapagliflozinParticipants will receive daily oral dose of dapagliflozin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- ≥ 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zibotentan/DapagliflozinParticipants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to | Drug | Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B |
| DapagliflozinParticipants will receive monotherapy dapagliflozin as per the arms they are randomized to | Drug | Dapagliflozin alone |
Primary outcome
Change in log-transformed Urinary Albumin to Creatinine Ratio (UACR) from baseline
Time frame: At Week 12
To estimate the efficacy of zibotentan and dapagliflozin in FDC versus dapagliflozin alone in reducing albuminuria
3 secondary outcomes
Change in log-transformed Urinary Protein to Creatinine Ratio (UPCR) from baseline
Time frame: At Week 12
Change in systolic and diastolic blood pressure (BP) from baseline
Time frame: At Week 12
Number of participants experiencing adverse events
Time frame: From Week 1 (Day 1) until Follow-up visit (Week 18, Day 112)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Related trials for Chronic Kidney Disease With High Proteinuria
Active, not recruitingPhase 3
Study to Investigate Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin in Participants With Chronic Kidney Disease and High Proteinuria (ZENITH High Proteinuria)
Chronic Kidney Disease With High Proteinuria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zibotentan/Dapagliflozin and Dapagliflozin in people with Chronic Kidney Disease With High Proteinuria, run by AstraZeneca at 14 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in log-transformed Urinary Albumin to Creatinine Ratio (UACR) from baseline (time frame: At Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.