Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema 2.4 mg/2.4 mg) Once Weekly Versus Semaglutide 2.4 mg, Cagrilintide 2.4 mg and Placebo in People With Chronic Kidney Disease and Type 2 Diabetes Living With Overweight or Obesity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 626
- 试验地点
- 118
- 主要终点
- Change in urinary albumin-to-creatinine ratio (UACR)
研究概览
简要总结
This study will look if CagriSema can lower kidney damage in people with chronic kidney disease (CKD), type 2 diabetes (T2D) and overweight or obesity. CagriSema is a new investigational medicine. CagriSema cannot yet be prescribed by doctors. The study will compare CagriSema to the 2 medicines semaglutide and cagrilintide, when they are taken alone. It will also compare CagriSema to a "dummy" medicine (also called placebo) without any active ingredient. Participant will either get CagriSema, semaglutide, cagrilintide or placebo. Which treatment participant will get is decided by chance (like flipping a coin). Study doctor will not know which of the study medicines participant will get. For each participant, the study will last for about 35 weeks.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female.
- •Age 18 years or above at the time of signing the informed consent.
- •Diagnosed with type 2 diabetes mellitus ≥ 180 days before screening.
- •Body mass index (BMI) ≥ 27.0 kilograms per meter square (kg/m^2) at screening. BMI will be calculated in the eCRF (electronic case report form) based on height and body weight at screening.
- •HbA1c less than or equal to (≤) 10.5% (91 millimoles per mole [mmol/mol]) as assessed by central laboratory at screening.
- •Kidney impairment defined by serum creatinine and cystatin C-based eGFR ≥ 15 and < 90 milliliters per minutes per 1.73^m^2 (mL/min/1.73 m^2) (CKD-EPI 2021) as assessed by central laboratory at screening.
- •Albuminuria defined by UACR ≥ 100 and < 5000 milligram per gram (mg/g) as assessed by central laboratory at screening.
- •Treatment with maximum labelled or tolerated dose of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated, in the opinion of the investigator. Treatment dose must be stable for at least 30 days prior to screening.
排除标准
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
- •Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations.
- •Use of any glucagon-like peptide-1 receptor agonist (GLP-1RA) (including medication with GLP-1RA activity, e.g., GIP/GLP-1RA) or amylin analogue within 60 days prior to screening.
- •Myocardial infarction, stroke, transient ischaemic attack, or hospitalization for unstable angina pectoris within 60 days before screening.
- •Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening.
- •Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- •Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in-situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN) within 5 years before screening.
研究组 & 干预措施
CagriSema
Participants will receive cagrilintide and semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.
干预措施: Cagrilintide (Drug)
CagriSema
Participants will receive cagrilintide and semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.
干预措施: Semaglutide (Drug)
Semaglutide
Participants will receive semaglutide and placebo matched to cagrilintide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.
干预措施: Semaglutide (Drug)
Semaglutide
Participants will receive semaglutide and placebo matched to cagrilintide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.
干预措施: Placebo (Drug)
Cagrilintide
Participants will receive cagrilintide and placebo matching to semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.
干预措施: Cagrilintide (Drug)
Cagrilintide
Participants will receive cagrilintide and placebo matching to semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.
干预措施: Placebo (Drug)
Placebo
Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide subcutaneously once weekly for 26 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in urinary albumin-to-creatinine ratio (UACR)
时间窗: From baseline (week 0) to end of treatment (week 26)
Measured in ratio to baseline.
次要结局
- Achievement of greater than or equal to (≥) 5 % weight reduction(From baseline (week 0) to end of treatment (week 26))
- Achievement of ≥ 10 % weight reduction(From baseline (week 0) to end of treatment (week 26))
- Change in estimated glomerular filtration rate (eGFR) (creatinine and cystatin C-based chronic kidney disease (CKD)-Epidemiology Collaboration equation (EPI) 2021)(From baseline (week 0) to end of treatment (week 26))
- Relative change in body weight(From baseline (week 0) to end of treatment (week 26))
- Change in waist circumference(From baseline (week 0) to end of treatment (week 26))
- Change in eGFR (creatinine-based CKD-EPI 2021)(From baseline (week 0) to end of treatment (week 26))
- Change in diastolic blood pressure(From baseline (week 0) to end of treatment (week 26))
- Number of treatment emergent adverse events (TEAEs)(From baseline (week 0) to end of study (week 32))
- Number of treatment emergent serious adverse events (SAEs)(From baseline (week 0) to end of study (week 32))
- Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold(From baseline (week 0) to end of study (week 32))
- Number of clinically significant hypoglycaemic episodes (level 2) ( blood glucose less than [<] 3.0 millimoles per liter [mmol/L] (54 milligram per deciliter [mg/dL]))(From baseline (week 0) to end of study (week 32))
- Change in glycated haemoglobin (HbA1c)(From baseline (week 0) to end of treatment (week 26))
- Change in systolic blood pressure(From baseline (week 0) to end of treatment (week 26))