NCT06087835Active, not recruitingPhase 3
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
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- AstraZeneca
- Enrollment
- 1,835
- Locations
- 301
- Primary Endpoint
- Change in eGFR from baseline
Study Overview
Brief 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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 95 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •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).
- •All female participants must have a negative serum pregnancy test result at screening.
- •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
- •Capable of giving signed informed consent
- •Provision of signed informed consent prior to any study specific procedure.
- •Provision of electronic informed consent prior to completion of the optional Study Participant Feedback Questionnaire (SPFQ).
- •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.
- •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 Criteria
- •Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
- •Participants hospitalised for HF during the last 6 month prior to screening.
- •Evidence of rales or jugular venous distention on physical examination.
- •Participants with type 1 diabetes mellitus.
- •History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
- •Blood pressure above 160 mmHg systolic.
- •Blood pressure below 90 mmHg systolic.
- •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.
- •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).
- •Any condition with a life expectancy of less than 2 years 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 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.
- •Known blood-borne diseases.
- •Clinically significant, unstable, or uncontrolled medical condition as assessed by the Investigator.
- •Participants on renal replacement therapy or previous kidney transplant.
- •Known history of drug or alcohol abuse within 12 months of screening.
- •Participants on treatment with strong or moderate CYP3A4 inducer.
- •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
- •Inhaled, nasal or dermatological steroids are also allowed.
- •Participants treated or expecting to be treated with tolvaptan, any other ERAs, or budesonide (where used to treat IBD or IgAN).
- •Participation in another clinical study with a study intervention administered in the last 3 months.
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- •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.
- •Previous randomisation in the present study.
- •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 procedures.
Arms & Interventions
Dapagliflozin alone
Active Comparator
Participants will receive daily oral dose of dapagliflozin.
Intervention: Dapagliflozin (Drug)
Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B
Experimental
Drug dose (dose A or B) are determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination.
Intervention: Zibotentan/Dapagliflozin (Drug)
Outcomes
Primary Outcomes
Change in eGFR from baseline
Time Frame: At month 24
To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone to slow decline in kidney function
Secondary Outcomes
- Change in Urine Albumin to Creatinine Ratio (UACR) from baseline(at Month 9)
- Change in Urine Protein to Creatinine Ratio (UPCR) from baseline(at Month 9)
- Change in Urine Albumin to Creatinine Ratio (UACR) from baseline to each participant's mean level(at Month 9)
- 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(Through study completion, approximately 38 months)
- Change in Urine Protein to Creatinine Ratio (UPCR) from baseline to each participant's mean level(at Month 9)
Investigators
Study Sites (301)
Loading locations...
Similar Trials
Not yet recruiting
Phase 3
A Study to Assess the Prevention of Bone-related Events in Patients With Bone Metastases From Malignant Solid Tumors Treated With JMT103 Compared to Zoledronic AcidImaging Examination Shows at Least One Site With Bone Metastases From Soild TumorsNCT06221072Shanghai JMT-Bio Inc.1,360
Completed
Phase 3
Efficacy and Safety of Pasireotide Administered Monthly in Patients With Cushing's DiseaseCushing's DiseaseNCT01374906Novartis Pharmaceuticals150
Completed
Phase 3
Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab in Patients With HER2 Positive Breast CancerHER2-positive Breast CancerNCT03588091Jiangsu HengRui Medicine Co., Ltd.355
Unknown
Phase 3
A Efficacy and Safety Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy Versus Placebo Combined With Chemotherapy as First-line Treatment in Subjects With Advanced Non-squamous Cell Non-small Cell Lung CancerAdvanced Non-squamous Cell Non-small Cell Lung CancerNCT04439890Chia Tai Tianqing Pharmaceutical Group Co., Ltd.369
Completed
Phase 3
Safety of Daily Dose Esomeprazole for GERD for Pediatric and Adolescent PatientsGastroesophageal Reflux Disease (GERD)NCT00241501AstraZeneca140