NCT06942910

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

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
224

participants targeted

Target at P75+ for phase_2

Timeline
3mo left

Started May 2025

Shorter than P25 for phase_2

Geographic Reach
1 country

15 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress81%
May 2025Jul 2026

First Submitted

Initial submission to the registry

April 17, 2025

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 24, 2025

Completed
13 days until next milestone

Study Start

First participant enrolled

May 7, 2025

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2026

Last Updated

April 17, 2026

Status Verified

March 1, 2026

Enrollment Period

1.2 years

First QC Date

April 17, 2025

Last Update Submit

April 14, 2026

Conditions

Chronic Kidney Disease With High Proteinuria

Keywords

ZibotentanNephrologyDapagliflozinSodium-glucose co-transporter 2sodium-glucose co-transporter 2 inhibitorKidney diseasesEndothelin antagonistHigh Proteinuria

Outcome Measures

Primary Outcomes (1)

  • 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

    At Week 12

Secondary Outcomes (3)

  • Change in log-transformed Urinary Protein to Creatinine Ratio (UPCR) from baseline

    At Week 12

  • Change in systolic and diastolic blood pressure (BP) from baseline

    At Week 12

  • Number of participants experiencing adverse events

    From Week 1 (Day 1) until Follow-up visit (Week 18, Day 112)

Other Outcomes (3)

  • Change in estimated Glomerular Filtration Rate (eGFR) from baseline

    At Week 12

  • Proportion of participants achieving Urine Protein to Creatinine Ratio (UPCR) < 1000 mg/g and > 30% reduction from baseline

    Across the visits from Week 2 (Day 14) up to Week 12 (Day 84)

  • Proportion of participants achieving Urinary Albumin to Creatinine Ratio (UACR) < 300 mg/g

    Across the visits from Week 2 (Day 14) up to Week 12 (Day 84)

Study Arms (2)

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.

Drug: Zibotentan/Dapagliflozin

Dapagliflozin alone

ACTIVE COMPARATOR

Participants will receive daily oral dose of dapagliflozin.

Drug: Dapagliflozin

Interventions

Zibotentan/DapagliflozinDRUG

Participants will receive zibotentan/dapagliflozin in fixed-dose combination as per the arms they are randomized to

Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B
DapagliflozinDRUG

Participants will receive monotherapy dapagliflozin as per the arms they are randomized to

Dapagliflozin alone

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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.

You may not qualify if:

  • 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.
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Research Site

Aramil, 624002, Russia

RECRUITING

Research Site

Izhevsk, 426061, Russia

SUSPENDED

Research Site

Krasnoyarsk, 660062, Russia

RECRUITING

Research Site

Moscow, 105554, Russia

SUSPENDED

Research Site

Moscow, 111539, Russia

RECRUITING

Research Site

Moscow, 117036, Russia

RECRUITING

Research Site

Moscow, 129327, Russia

RECRUITING

Research Site

Omsk, 644112, Russia

RECRUITING

Research Site

Orenburg, 460018, Russia

RECRUITING

Research Site

Perm, 614000, Russia

RECRUITING

Research Site

Saint Petersburg, 195067, Russia

SUSPENDED

Research Site

Saratov, 410053, Russia

RECRUITING

Research Site

Saratov, 410054, Russia

RECRUITING

Research Site

Ulyanovsk, 432009, Russia

RECRUITING

Research Site

Yaroslavl, 150062, Russia

RECRUITING

MeSH Terms

Conditions

Kidney Diseases

Interventions

ZD4054dapagliflozin

Condition Hierarchy (Ancestors)

Urologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479information.center@astrazeneca.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 17, 2025

First Posted

April 24, 2025

Study Start

May 7, 2025

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

July 31, 2026

Last Updated

April 17, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at : https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

Locations

RU(15)