A Phase 2, Open-Label, Basket Study of Atrasentan in Patients With Proteinuric Glomerular Diseases
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 103
- 试验地点
- 48
- 主要终点
- Change in proteinuria for IgAN, FSGS, and Alport syndrome patients receiving 0.75 mg atrasentan QD
研究概览
简要总结
The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function.
详细描述
The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function. Cohorts will consist of patients with:
- IgA nephropathy (IgAN) with urine protein:creatinine ratio (UPCR) of 0.5 to less than 1.0 g/g
- Focal segmental glomerulosclerosis (FSGS)
- Alport syndrome
- Diabetic kidney disease (DKD) on top of background care of a RAS inhibitor and SGLT2 inhibitor
Additional cohorts may be added as data is available.
Approximately 100 patients will be enrolled in the study. Approximately 20 patients will be enrolled in each cohort to receive 0.75 mg atrasentan QD for 52 weeks. The study will also evaluate efficacy and safety of 1.5 mg atrasentan QD in FSGS subjects who received 0.75 mg atrasentan and it was well tolerated.
Patients will be allowed to continue into treatment extension and receive oral atrasentan QD for up to an additional 84 weeks (total maximum treatment of 188 weeks),
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Age 18 years and older for patients in the IgAN, FSGS, and Alport Syndrome cohorts
- •Age 18-70 years for patients in the DKD cohort
- •Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks.
- •For patients enrolling in IgAN Cohort:
- •Biopsy-proven IgA nephropathy
- •UPCR between 0.5 to less than 1.0 g/g
- •Screening eGFR ≥ 30 mL/min/1.73 m2
- •For patients enrolling in FSGS Cohort:
- •Biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS
- •UPCR > 1.0 g/g
- •Screening eGFR ≥ 30 mL/min/1.73 m2
- •Subjects receiving systemic corticosteroids or other immunosuppressants must be on a stable dose for at least 12 weeks.
- •BMI ≤ 40 kg/m2
- •For patients enrolling in Alport syndrome Cohort:
- •Diagnosis of Alport syndrome by genetic testing
- •UPCR > 0.5 g/g
- •Screening eGFR ≥ 30 mL/min/1.73 m2
- •For patients enrolling in DKD Cohort:
- •Diagnosis of type 2 diabetes mellitus
- •UACR ≥ 0.5 g/g
- •Screening eGFR ≥ 45 mL/min/1.73 m2
- •Receiving a stable dose of SGLT2 inhibitor for at least 12 weeks
- •Willing and able to provide informed consent and comply with all study requirements
排除标准
- •Current diagnosis of another cause of chronic kidney disease or another primary glomerulopathy.
- •History of kidney transplantation or other organ transplantation.
- •Except for FSGS patients, use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months.
- •Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator.
- •History of heart failure or a previous hospital admission for fluid overload.
- •Clinically significant history of liver disease as assessed by the Investigator.
- •Hemoglobin below 9 g/dL as measured by the Investigator or blood transfusion for anemia within the past 3 months.
- •Clinical diagnosis of nephrotic syndrome
- •Malignancy within the past 5 years. Exception to the criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ.
- •For women, pregnant, breastfeeding, or intent to become pregnant during the study.
- •For men, intent to father a child or donate sperm during the study.
- •Recently received an investigational agent.
- •Clinically significant unstable or uncontrolled medical condition as assessed by the Investigator.
研究组 & 干预措施
Atrasentan 0.75 mg
Once daily oral administration of 0.75 mg atrasentan
干预措施: Atrasentan (Drug)
Atrasentan 1.5 mg
Once daily oral administration 1.5 mg atrasentan (FSGS cohorts only)
干预措施: Atrasentan (Drug)
结局指标
主要结局
Change in proteinuria for IgAN, FSGS, and Alport syndrome patients receiving 0.75 mg atrasentan QD
时间窗: Up to Week 12 or approximately 3 months
The change in urine protein:creatinine ratio (UPCR) from baseline to Week 12
Change in albuminuria for DKD patients
时间窗: Up to Week 12 or approximately 3 months
The change in urine albumin:creatinine ratio (UACR) from baseline to Week 12
Change in proteinuria for FSGS patients at 1.5 mg dose
时间窗: Up to Week 30 or approximately 7.5 months
The change in urine protein:creatinine ratio (UPCR) from baseline to Week 30
次要结局
未报告次要终点