A 6-month Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and PK/PD of an age-and Body Weight-adjusted Oral Finerenone Regimen, in Addition to an ACEI or ARB, for the Treatment of Children, 6 Months to <18 Years of Age, With Chronic Kidney Disease and Proteinuria
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 219
- 试验地点
- 389
- 主要终点
- Percent change in Urinary protein-to-creatinine ratio (UPCR) reduction from baseline to day 180+/-7
研究概览
简要总结
Researchers are looking for a better way to treat children who have chronic kidney disease (CKD), which is long-term kidney disease, and proteinuria, a condition in which a person´s kidneys leak protein into the urine.
The kidneys filter waste and fluid from the blood to form urine. In children with CKD, the kidney´s filters do not work as well as they should. This can lead to accumulation of waste and fluid in the body and proteinuria. CKD can lead to other medical problems, such as high blood pressure, also known as hypertension. Vice versa, hypertension and proteinuria can also contribute to worsening of CKD. Therefore, the treatment of CKD aims to control blood pressure and proteinuria. There are treatments available for doctors to prescribe to children with CKD and hypertension and/or proteinuria. These include "angiotensin-converting enzyme inhibitors" (ACEI) and "angiotensin receptor blockers" (ARB). Both ACEI and ARB can improve kidney function by helping the renin-angiotensin-aldosterone system (RAAS) to work normally. The RAAS is a system that works with the kidneys to control blood pressure and the balance of fluid and electrolytes in the blood. In people with CKD, the RAAS is often too active, which can stop the kidneys from working properly and cause hypertension and proteinuria. However, ACEI or ARB treatment alone does not work for all patients with CKD as they only target the angiotensin part of the renin-angiotensin-aldosterone system.
The study treatment, finerenone, is expected to help control RAAS overactivation together with an ACEI or ARB.
So, the researchers in this study want to learn more about whether finerenone given in addition to either an ACEI or ARB can help their kidney function.
The main purpose of this study is to learn more about whether finerenone added to either ACEI or ARB can help reduce the amount of protein in the participants' urine more than a placebo. A placebo looks like a treatment but does not have any medicine in it. Participants will also continue to receive their other medications.
To see how the treatment work, the doctors will take samples of the participants' urine to measure their protein levels before and during taking treatment and after their last treatment. In addition, blood samples will be taken to monitor kidney function, electrolytes and the amount of finerenone in the blood as well as for other tests.
This study will include children with CKD and proteinuria aged from 6 months up to less than 18 years. The participants will take:
- either finerenone or the placebo, in addition to
- either ACEI or ARB, whichever they take as part of their normal treatment
Two visits are required up to 104 days, to check whether a child can take part in the treatment phase of the study. If participants qualify for the treatment phase, they will then undergo treatment for about 180 days. During this time, they will visit the study site at least 7 times. During these visits, the participants will:
- have their blood pressure, heart rate, temperature, height and weight measured
- have blood and urine samples taken
- have physical examinations
- have their heart examined by an electrocardiogram and echocardiography (a sonogram of the heart)
- answer questions about their medication and whether they have any adverse events , or have their parents or guardians answer
- answer questions about how they are feeling, or have their parents or guardians answer
- answer question about how they like the study medication, or have their parents or guardians answer
The doctors will keep track of any adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
The doctors will check the participants' health about 30 days after the participants take their last treatment.
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
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be 6 months to <18 years old at the time when the informed consent/assent is signed
- •Participants must have a clinical diagnosis of chronic kidney disease (CKD) at screening which is defined as
- •CKD stages 1-3 (eGFR ≥30 mL/min/1.73m^2) for children ≥1 year to <18 years of age or
- •a serum creatinine ≤ 0.40 mg/dL for infants 6 months to < 1 year of age and
- •severely increased proteinuria as defined by
- •Urinary protein-to-creatinine ratio (UPCR) of ≥ 0.50 g/g in participants ≥ 2 years with CKD stage 2 and 3 or
- •UPCR ≥ 1.0 g/g for patients < 2 years of age or ≥ 2 years of age and with CKD stage 1
- •Participants must have stable kidney function between screening and D0 defined as:
- •For participants with a creatinine of > 0.8 mg/dL at screening: no increase or decrease in eGFR by ≥ 20% at D0
- •For participants with a creatinine of ≤ 0.8 mg/dL at screening: no increase or decrease in creatinine ≥ 0.15 mg/dL at D
- •Treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at optimized doses defined as maximally tolerable doses within the recommended dose range according to guidelines on blood pressure management, unchanged for at least 30 days prior to screening
- •K+ ≤5.0 mmol/L for children ≥2 years of age at both screening and D0, and ≤5.3 mmol/L for children <2 years of age at both screening and D0
排除标准
- •Planned urological surgery expected to influence renal function
- •Children with hemolytic uremic syndrome (HUS) diagnosed ≤6 months prior to screening
- •Patients with nephrotic syndrome receiving albumin infusions within the last 6 months prior to screening
- •Patients who are candidates for renal transplantation, i.e., a kidney transplantation scheduled within the study time frame
- •Renal allograft in place
- •Bilateral renal artery stenosis
- •Acute kidney injury requiring dialysis within 6 months prior to screening
- •Systemic hypertension stage 2 in children ≥1 year of age defined according to guidelines on blood pressure management at screening or randomization
- •Systolic blood pressure (SBP) above 110 mmHg in infants 6 months to <1 year of age at screening or randomization
- •Systemic hypotension defined as a systolic blood pressure below the 5th percentile for age, sex and height at either screening or randomization but no lower than 80 mmHg (although for some participants the 5th percentile of SBP is < 80 mmHg they must be excluded if their SBP is <80 mmHg)
- •Participants with immune-mediated CKD using rituximab, cyclophosphamide, abatacept, or high-dose glucocorticoids, within <6 months prior to screening
研究组 & 干预措施
Placebo
Participants will receive placebo to finerenone.
干预措施: Placebo (Drug)
Finerenone (Kerendia, BAY94-8862)
Participants will receive finerenone treatment.
干预措施: Finerenone (Kerendia, BAY94-8862) (Drug)
结局指标
主要结局
Percent change in Urinary protein-to-creatinine ratio (UPCR) reduction from baseline to day 180+/-7
时间窗: From baseline to day 180+/-7
Percent change from baseline to day 180±7 in UPCR will be calculated.
次要结局
- Change in systolic blood pressure from baseline to day 180±7(From baseline to day 180±7)
- Pharmacokinetics (PK) finerenone Cmax, md(Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7)
- Number participants with treatment emergent adverse events (TEAEs）(From the start of study intervention to last study intervention + 3 days (up to 190 days))
- Change in eGFR from baseline to day 180±7(From baseline to day 180±7)
- Taste and texture questionnaire of the pediatric formulation(On day 30±3 and day 180±7)
- Change in serum potassium levels from baseline to day 180±7(From baseline to day 180±7)
- Change in serum creatinine from baseline to day 180±7(From baseline to day 180±7)
- Change in UACR from baseline to day 180±7(From baseline to day 180±7)
- Pharmacokinetics (PK) finerenone AUCτ,md(Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7)
- UPCR reduction of at least 30% from baseline to day 180+/-7(From baseline to day 180±7)