2025-522824-29-00招募中3 期
A single-arm, multicenter, phase III study to assess efficacy, pharmacokinetics, safety and tolerability of atrasentan in pediatric patients of 2 to <18 years of age with primary immunoglobulin A nephropathy (IgAN)
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 8
- 主要终点
- Change in proteinuria (natural log UPCR* sampled from FMV urine collection) from Baseline to Week 36 (all cohorts combined)
研究概览
简要总结
To evaluate the effect of atrasentan in reducing proteinuria from Baseline to Week 36 by measuring urinary protein to creatinine ratio (UPCR) sampled from first morning void (FMV) in the overall study population.
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Participants 2 to <18 years of age as of Day
- •eGFR ≥30 mL/min/1.73m2 where eGFR is calculated using the modified Schwartz formula at Screening and confirmed at Run-in period.
- •Kidney biopsy-proven primary IgAN with biopsy performed within 3 years of Screening with < 50% tubulointerstitial fibrosis and <25% crescents.
- •Proteinuria due to primary diagnosis of IgAN as assessed by UPCR ≥ 1 g/g (113 mg/mmol) sampled from FMV (or in exceptional cases spot urine for participants in cohorts 2, 3 or 4) at Screening, on Day −90 and Day −60 as well as during the Run-in Period despite treatment with maximum tolerated dose of ACE inhibitor/ARB for at least 120 days prior to Day
- •All participants must have been on supportive care including stable dose regimen of ACE inhibitor or ARB at either the locally approved maximal daily dose per body weight, or the maximally tolerated dose (per investigators’ judgment for pediatric use), for at least 120 days before first study drug administration. In addition, if participants are taking diuretics, other antihypertensive medication, other background medication for IgAN (such as SGLT2 inhibitors) or other medications that could affect UPCR levels (such as GLP-1 agonists), the doses should also be stabilized for at least 120 days prior to the first dosing of study treatment.
- •The minimum body weight of enrolled pediatric participants is 10 kg at Screening and confirmed on Day 1.
排除标准
- •Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, Herpes Simplex virus infection, dermatitis herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, inflammatory bowel disease, and familial mediterranean fever.
- •On Day 1 participants’ body weight falls below the lower limit of the cohort in which the participant was initially screened and lower body weight cohort is not open for enrollment.
- •Known history of congenital heart disease, heart failure or clinically significant fluid retention such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites.
- •Current use of any homeopathic and/or herbal medications for the treatment of IgAN disease, such as but not limited to Tripterygium wilfordii (Lei Gong Teng), Caulis sinomenii and Sinomenium acutum.
- •Confirmed blood pressure >150 mmHg systolic or >95 mmHg diastolic for 12 to <18 years of age; >140 mmHg systolic or >90 mmHg diastolic for 6 to <12 years of age; >120 mmHg systolic or >80 mmHg diastolic for 2 to <6 years of age; based on the mean of 3 measurements obtained at Screening; or clinically significant hypotension at screening.
- •Participants previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), calcineurin inhibitors, complement inhibitors, oral budesonide in any dose, systemic corticosteroid exposure ≥0.5 mg/kg/day or > 7.5 mg total exposure in a single day of prednisone/prednisolone equivalent within 120 days (or 180 days for rituximab) prior to first study drug administration. Participants treated with endothelin (receptor) antagonists (including sparsentan) within 120 days prior to first study drug administration.
- •Major concurrent comorbidities including but not limited to advanced cardiac disease (e.g., NYHA class III (for ages 6 to <18 years), Ross class III (for ages 2 to <6years)), severe pulmonary disease (e.g., WHO class III (for age 17 years); Pulmonary Vascular Research Institute (PVRI) class III (for 2-<17 years)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes subject's participation in the study.
- •A clinical diagnosis of IgA vasculitis (IgAV or Henoch-Schoenlein purpura) based on typical palpable purpura with or without arthralgia and abdominal pain.
- •Evidence of significant urinary obstruction or difficulty in voiding, any urinary tract disorder causing significant urinary obstruction or difficulty in voiding at Screening and confirmed at Baseline/Day
- •Current acute kidney injury (AKI) defined by Acute Kidney Injury Network (AKIN) criteria within 4 weeks of Screening.
- •Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to Screening or during Screening and Run-in periods.
- •Presence of nephrotic syndrome at Screening based on the investigator’s judgement.
- •BNP value of >200 pg/mL at Screening.
- •Hemoglobin below 9 g/dL at Screening or prior history of blood transfusion for anemia within 3 months of Screening.
- •Platelet count <80,000/µL at Screening.
结局指标
主要结局
Change in proteinuria (natural log UPCR* sampled from FMV urine collection) from Baseline to Week 36 (all cohorts combined)
Change in proteinuria (natural log UPCR* sampled from FMV urine collection) from Baseline to Week 36 (all cohorts combined)
次要结局
- Change in proteinuria (natural log UPCR* sampled from FMV urine collection) from Baseline to Week 36 (in participants with ≤ 30% decrease in proteinuria during the 60-day period prior to atrasentan initiation, all cohorts combined)
- PK parameters Cmaxss, AUCss, CLss/F (and other PK parameters in plasma, as appropriate), and Ctrough concentrations.
- Safety endpoints (including AEs, SAEs, laboratory parameters, and vital signs)
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (8)
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