PDF(Pubmed)
Abstract：
UNASSIGNED: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS).
UNASSIGNED: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively.
UNASSIGNED: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes.
UNASSIGNED: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.
UNASSIGNED: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively.
UNASSIGNED: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes.
UNASSIGNED: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.
摘要：
■DUPLEX第3阶段试验正在评估Sparsentan，一本小说,非免疫抑制,单分子双内皮素血管紧张素受体拮抗剂，局灶节理性肾小球硬化（FSGS）患者。
■DUPLEX(NCT03493685)是一个全球性的，多中心，随机化，双盲,平行组，活性对照研究评估斯帕生坦800mg每天一次与厄贝沙坦300mg每天一次在8至75岁（美国/英国）和18至75岁（美国/英国除外）体重≥20kg的患者中的疗效和安全性。活检证实的FSGS或与FSGS相关的足细胞蛋白中的基因突变，尿蛋白肌酐比值（UP/C）≥1.5g/g。描述性报道了对治疗分配盲化的基线特征。
■主要分析人群包括371名患者（336名成人，35名儿科[<18岁])随机分组并接受研究药物(中位年龄，42年）。患者为白人（73.0%），亚洲（13.2%），黑人/非洲裔美国人（6.7%），或其他种族(7.0%)；北美(38.8%)，欧洲（36.1%），南美洲（12.7%），或亚太地区（12.4%）。基线中位数UP/C为3.0g/g；肾病范围为42.6％（UP/C>3.5g/g[成人]；>2.0g/g[儿科]）。患者均匀分布在估计的肾小球滤过率（eGFR）类别中，对应于慢性肾病（CKD）阶段1至3b。33例患者（352个可评估样本中的9.4％）具有足细胞结构完整性和功能必需基因的致病性或可能致病性（P/LP）变异，27例(7.7%)有P/LP胶原基因(COL4A3/4/5)变异,和14（4.0％）有高风险的APOL1基因型。
■DUPLEX患者登记，FSGS迄今为止最大的介入研究，将能够在地理上广泛和临床上多样化的FSGS人群中对sparsentan的治疗效果进行重要表征。
■DUPLEX(NCT03493685)是一个全球性的，多中心，随机化，双盲,平行组，活性对照研究评估斯帕生坦800mg每天一次与厄贝沙坦300mg每天一次在8至75岁（美国/英国）和18至75岁（美国/英国除外）体重≥20kg的患者中的疗效和安全性。活检证实的FSGS或与FSGS相关的足细胞蛋白中的基因突变，尿蛋白肌酐比值（UP/C）≥1.5g/g。描述性报道了对治疗分配盲化的基线特征。
■主要分析人群包括371名患者（336名成人，35名儿科[<18岁])随机分组并接受研究药物(中位年龄，42年）。患者为白人（73.0%），亚洲（13.2%），黑人/非洲裔美国人（6.7%），或其他种族(7.0%)；北美(38.8%)，欧洲（36.1%），南美洲（12.7%），或亚太地区（12.4%）。基线中位数UP/C为3.0g/g；肾病范围为42.6％（UP/C>3.5g/g[成人]；>2.0g/g[儿科]）。患者均匀分布在估计的肾小球滤过率（eGFR）类别中，对应于慢性肾病（CKD）阶段1至3b。33例患者（352个可评估样本中的9.4％）具有足细胞结构完整性和功能必需基因的致病性或可能致病性（P/LP）变异，27例(7.7%)有P/LP胶原基因(COL4A3/4/5)变异,和14（4.0％）有高风险的APOL1基因型。
■DUPLEX患者登记，FSGS迄今为止最大的介入研究，将能够在地理上广泛和临床上多样化的FSGS人群中对sparsentan的治疗效果进行重要表征。
