Efficacy, Safety and Pharmacokinetics of NNC0519-0130 Once Weekly s.c. Versussemaglutide 1.0 mg and Placebo in People With Chronic Kidney Disease, With or Without Type 2 Diabetes, and With Overweight or Obesity: a Proof-of-concept and Dose-finding Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 465
- 试验地点
- 267
- 主要终点
- Change in urinary albumin-to-creatinine ratio (UACR) at week 12
研究概览
简要总结
The study evaluates the safety of different doses of a new medicine called NNC0519 0130. It also looks into how the medicine may improve kidney function in participants with chronic kidney disease with or without type 2 diabetes, living with overweight or obesity. The participants will either get NNC0519-0130 (a new medicine), semaglutide (a medicine that doctors can already prescribe), or placebo (a "dummy" substance). Which treatment the participant will get is decided by chance. The study will last for up to 43 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)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
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
- •Female of non-childbearing potential, or male.
- •For US only: Female of childbearing potential using highly effective non-systemic methods of contraception with low user-dependency at least 2 months prior to screening and willingness to continue using it through-out the study, or male.
- •Age 18 years or above at the time of signing the informed consent.
- •Diagnosed with type 2 diabetes mellitus greater than or equal to (≥) 180 days before screening, or not diagnosed with type 2 diabetes mellitus.
- •HbA1c of 6.5 percentage (%)-10.5 percentage (%) [48 - 91 millimoles per mole (mmol/mol)] (both inclusive) if diagnosed with type 2 diabetes mellitus, or HbA1c of less than (<)6.5 percentage (%) [<48 mmol/mol] if not diagnosed with type 2 diabetes mellitus.
- •BMI greater than or equal to (≥) 27.0 kilogram per square metre (kg/m^2) at screening.
- •Kidney impairment defined by serum creatinine and cystatin C-based Egfr greater than or equal to (≥) 15 and less than (<) 90 mL/min/1.73 m^
- •Albuminuria defined by Urine Albumin-to-Creatinine Ratio (UACR) greater than or equal (≥)100 and less than (<) 5000 milligram per gram (mg/g).
- •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 highly effective non-systemic contraception with low user-dependency.
- •Lupus nephritis or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
- •Receiving immunosuppressive therapy for primary or secondary renal disease within 6 months prior to screening.
- •Use of any glucagon-like peptide-1 (GLP-1) RA (including medication with GLP-1 RA activity, e.g., GIP/GLP-1 RA) within 90 days prior to screening.
- •Myocardial infarction, stroke, transient ischaemic attack, or hospitalization for unstable angina pectoris within 180 days before screening.
- •Chronic or intermittent haemodialysis or peritoneal dialysis within 90 days before screening.
- •Only applicable for participants with type 2 diabetes (T2D): Uncontrolled and potentially unstable diabetic retinopathy or diabetic 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
Dosing scheme a: NNC0519-0130
Participants will receive once-weekly subcutaneous (s.c) injections of NNC0519-0130 following a fixed dose escalation until the maintenance dose is reached.
干预措施: NNC0519-0130 (Drug)
Dosing scheme a: Placebo
Participants will receive NNC0519-0130 matched placebo s.c. once-weekly.
干预措施: Placebo (Drug)
Dosing scheme b: NNC0519-0130
Participants will receive once-weekly s.c injections of NNC0519-0130 following a fixed dose escalation until the maintenance dose is reached.
干预措施: NNC0519-0130 (Drug)
Dosing scheme b: Placebo
Participants will receive NNC0519-0130 matched placebo s.c. once-weekly.
干预措施: Placebo (Drug)
Dosing scheme c: NNC0519-0130
Participants will receive once-weekly s.c injections of NNC0519-0130 following a fixed dose escalation until the maintenance dose is reached.
干预措施: NNC0519-0130 (Drug)
Dosing scheme c: Placebo
Participants will receive NNC0519-0130 matched placebo s.c. once-weekly.
干预措施: Placebo (Drug)
Dosing scheme d: NNC0519-0130
Participants will receive once-weekly s.c injections of NNC0519-0130 following a fixed dose escalation until the maintenance dose is reached.
干预措施: NNC0519-0130 (Drug)
Dosing scheme d: Placebo
Participants will receive NNC0519-0130 matched placebo s.c. once-weekly.
干预措施: Placebo (Drug)
Dosing scheme e: Semaglutide
Participants will receive once-weekly s.c injections of semaglutide with a dose escalation done until maintenance dose is reached.
干预措施: Semaglutide (Drug)
结局指标
主要结局
Change in urinary albumin-to-creatinine ratio (UACR) at week 12
时间窗: From baseline (week 0) to end of a given maintenance dose period (week 12)
Measured as a ratio to baseline.
Change in urinary albumin-to-creatinine ratio (UACR) at week 24
时间窗: From baseline (week 0) to end of a given maintenance dose period (week 24)
Measured as a ratio to baseline.
Change in urinary albumin-to-creatinine ratio (UACR) at week 36
时间窗: From baseline (week 0) to end of a given maintenance dose period (week 36)
Measured as a ratio to baseline.
次要结局
- Change in estimated glomerular filtration rate (eGFR) (creatinine and cystatin C-based Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021)(From baseline (week 0) to end of treatment (week 36))
- Change in estimated glomerular filtration rate (eGFR) (creatinine-based CKD-EPI 2021)(From baseline (week 0) to end of treatment (week 36))
- Relative change in body weight(From baseline (week 0) to end of treatment (week 36))
- Achievement of greater than or equal to (≥) 5 percentage (%) weight reduction(From baseline (week 0) to end of treatment (week 36))
- Achievement of greater than or equal to (≥) 10 percentage (%) weight reduction(From baseline (week 0) to end of treatment (week 36))
- Change in waist circumference(From baseline (week 0) to end of treatment (week 36))
- Change in glycated haemoglobin (HbA1c)(From baseline (week 0) to end of a given maintenance dose period (week 12, 24 or 36))
- Change in systolic blood pressure(From baseline (week 0) to end of treatment (week 36))
- Change in diastolic blood pressure(From baseline (week 0) to end of treatment (week 36))
- Number of treatment emergent adverse events (TEAEs)(From baseline (week 0) to end of study (week 40))