NCT06087835进行中（未招募）3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,835
- 试验地点
- 301
- 主要终点
- Change in eGFR from baseline
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Dapagliflozin alone
Active Comparator
Participants will receive daily oral dose of dapagliflozin.
干预措施: 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.
干预措施: Zibotentan/Dapagliflozin (Drug)
结局指标
主要结局
Change in eGFR from baseline
时间窗: At month 24
To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone to slow decline in kidney function
次要结局
- 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)
研究者
研究点 (301)
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