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)

NCT06087835
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,835
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Lead sponsor
AstraZeneca
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Start date
2023-11-07
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Number of sites
296
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Summary
This is a Phase III, randomised, multicentre, double-blinded study to evaluate efficacy, safety and tolerability of treatment with zibotentan/dapagliflozin and dapagliflozin alone in participants with chronic kidney disease (CKD) and high proteinuria
clinicaltrials.gov
Short title
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)
clinicaltrials.gov
Official title
A Phase III, Randomised, Multicentre, Double-blind Study to Evaluate the Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin Alone in Participants With Chronic Kidney Disease and High Proteinuria
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2027-02-18
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First posted
2023-10-18
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Registry last updated
2026-08-19
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Primary completion date
2027-02-18
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Start date
2023-11-07
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Actual participants
1,835
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Participants
1,835
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Participant count basis
Actual
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Protocol amendments
6
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Number of sites
296
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06087835
clinicaltrials.gov
ClinicalTrials.gov ID
NCT06087835
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Change in eGFR from baseline

    Timeframe: At month 24

    To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone to slow decline in kidney function

  1. Change in Urine Albumin to Creatinine Ratio (UACR) from baseline

    Timeframe: at Month 9

    To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone in reducing albuminuria

  2. Time to the first occurrence of any of the components of the renal composite endpoint of 40% sustained decline in eGFR or ESKD or renal death

    Timeframe: Through study completion, approximately 38 months

    To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone in reducing the incidence of the renal composite endpoint of 40% sustained decline in eGFR or ESKD or renal death

  3. Change in Urine Protein to Creatinine Ratio (UPCR) from baseline

    Timeframe: at Month 9

    To determine whether zibotentan and dapagliflozin in FDC is superior to dapagliflozin alone in reducing proteinuria in the biopsy-confirmed IgAN subgroup

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
95 Years
Healthy volunteers
No

  1. Participant must be ≥ 18 years of age and of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.

  2. Diagnosis of CKD, defined as eGFR ≥ 20 and < 90 mL/min/1.73 m2 and UACR > 700 mg/g (> 79 mg/mmol) or UPCR > 1000 mg/g (> 113 mg/mmoL).

  3. All female participants must have a negative serum pregnancy test result at screening.

  4. Female participants must be either

    • not of child-bearing potential or
    • women of child bearing potential (WOCBP) using at least one highly effective birth control method for at least 3 months prior to first dose of study intervention

  5. Capable of giving signed informed consent

  6. Provision of signed informed consent prior to any study specific procedure.

  7. Provision of electronic informed consent prior to completion of the optional Study Participant Feedback Questionnaire (SPFQ).

  8. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics imitative research that supports the Genomic Initiative.

  9. Receiving RAASi therapy (ACEi or ARB), and for the patient maximum tolerated labelled daily dose, that has been stable for at least 4 weeks.

  1. Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
  2. Participants hospitalised for HF during the last 6 month prior to screening.
  3. Evidence of rales or jugular venous distention on physical examination.
  4. Participants with type 1 diabetes mellitus.
  5. History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
  6. Blood pressure above 160 mmHg systolic.
  7. Blood pressure below 90 mmHg systolic.
  8. Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening.
  9. History of solid organ transplantation or bone marrow transplant.
  10. History or ongoing allergy/hypersensitivity, as judged by the Investigator, to SGLT2i therapy (eg, dapagliflozin, canagliflozin, empagliflozin or other SGLT2 inhibitors) or Endothelin Receptor Antagonists (eg, ambrisentan, atrasentan, bosentan, or other).
  11. Any condition with a life expectancy of less than 2 years based on investigator´s clinical judgment.
  12. Malignancy within the past 5 years. Exceptions to this criterion include non-melanoma skin cancer and curatively treated cervical carcinoma in situ.
  13. Significant liver disease as judged by the investigator or severe hepatic impairment with AST or ALT > 3 × ULN; or total bilirubin > 2 × ULN at time of screening. An isolated increase in bilirubin in participants with known Gilbert's syndrome is not a reason for exclusion.
  14. Known blood-borne diseases.
  15. Clinically significant, unstable, or uncontrolled medical condition as assessed by the Investigator.
  16. Participants on renal replacement therapy or previous kidney transplant.
  17. Known history of drug or alcohol abuse within 12 months of screening.
  18. Participants on treatment with strong or moderate CYP3A4 inducer.
  19. Participants on systemic immunosuppression therapy other than stable maintenance therapy defined as prednisone 10 mg/day (or equivalent) or less, aziothioprine 100 mg/day or less; MMF 1000 mg/day or less for at least 3 months prior to Visit 1. Inhaled, nasal or dermatological steroids are also allowed.
  20. Participants treated or expecting to be treated with tolvaptan, any other ERAs, or budesonide (where used to treat IBD or IgAN).
  21. Participation in another clinical study with a study intervention administered in the last 3 months.
  22. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  23. Inability of the participant, in the opinion of the investigator, to understand and/or comply with IMP, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the participant unable to complete the study.
  24. Previous randomisation in the present study.
  25. Women who are pregnant, breast-feeding, or women with intent of getting pregnant.
  26. Women who are not willing to use adequate contraception or cannot, in the opinion of the investigator, understand and/or comply with the study procedures.
Sources for eligibility
clinicaltrials.gov

  • Research SiteHuntsville, United States
  • Research SiteSun City West, United States
  • Research SiteBakersfield, United States
  • Research SiteHuntington Park, United States
  • Research SiteLos Alamitos, United States
  • Research SiteLos Angeles, United States
  • Research SiteNorthridge, United States
  • Research SiteOxnard, United States
  • Research SiteSan Carlos, United States
  • Research SiteSan Dimas, United States
  • Research SiteTarzana, United States
  • Research SiteVictorville, United States
  • Research SiteArvada, United States
  • Research SiteDenver, United States
  • Research SiteBoynton Beach, United States
  • Research SiteHialeah, United States
  • Research SiteHollywood, United States
  • Research SiteJacksonville, United States
  • Research SiteJensen Beach, United States
  • Research SiteMiami, United States
  • Research SiteMiami, United States
  • Research SiteOrlando, United States
  • Research SiteFayetteville, United States
  • Research SiteChampaign, United States
  • Research SiteChicago, United States

And 271 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-504124-26
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (1)

Targets (2)