未经证实:补体3肾小球病(C3G)是一种罕见的肾脏疾病,其特征是补体系统的替代途径(AP)失调。大约50%的C3G患者在诊断后10年内进展为肾衰竭。目前,没有批准的C3G治疗剂。Iptacopan是一种口服,一流的,强力,和B因子的选择性抑制剂,AP的关键组成部分。在第二阶段的研究中,在具有天然肾脏和移植肾脏的C3G患者中,用伊塔科班治疗与蛋白尿和C3沉积物评分的降低相关。分别。
未经批准:APPEAR-C3G(NCT04817618)是一个随机的,双盲,和安慰剂对照的III期研究,以评估伊塔科潘在C3G患者中的疗效和安全性,招募68名活检证实为C3G的成年人,减少C3(<77mg/dl),蛋白尿≥1.0g/g,估计肾小球滤过率(eGFR)≥30ml/min/1.73m2。所有患者将接受最大耐受的血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂和针对包封细菌的疫苗接种。任何器官移植的患者,进行性新月体肾小球肾炎(GN),意义不明的单克隆丙种球蛋白病,或肾活检>50%间质纤维化/肾小管萎缩,将被排除在外。患者将以1:1的比例随机分配,每天两次服用200毫克的伊塔科潘或安慰剂,持续6个月。随后对所有患者进行200mg伊塔科潘每日2次开放标签治疗,共6个月.主要目的是评估伊塔科班与安慰剂对蛋白尿减少尿蛋白:肌酐比值(UPCR)(24小时尿液)的疗效。关键的次要终点将评估通过eGFR测量的肾功能,组织学疾病总活动评分,和疲劳。
UNASSIGNED:本研究旨在证明在C3G中使用伊托科班抑制AP的临床益处。
UNASSIGNED: Complement 3 glomerulopathy (C3G) is a rare kidney disease characterized by dysregulation of the alternative pathway (AP) of the complement system. About 50% of patients with C3G progress to kidney failure within 10 years of diagnosis. Currently, there are no approved therapeutic agents for C3G. Iptacopan is an oral, first-in-class, potent, and selective inhibitor of factor B, a key component of the AP. In a Phase II
study, treatment with iptacopan was associated with a reduction in proteinuria and C3 deposit scores in C3G patients with native and transplanted kidneys, respectively.
UNASSIGNED: APPEAR-C3G (NCT04817618) is a randomized, double-blind, and placebo-controlled Phase III
study to evaluate the efficacy and safety of iptacopan in C3G patients, enrolling 68 adults with biopsy-confirmed C3G, reduced C3 (<77 mg/dl), proteinuria ≥1.0 g/g, and estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m2. All patients will receive maximally tolerated angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and vaccination against encapsulated bacteria. Patients with any organ transplantation, progressive crescentic glomerulonephritis (GN), monoclonal gammopathy of undetermined significance, or kidney biopsy with >50% interstitial fibrosis/tubular atrophy, will be excluded. Patients will be randomized 1:1 to receive either iptacopan 200 mg twice daily or placebo for 6 months, followed by open-label treatment with iptacopan 200 mg twice daily for all patients for 6 months. The primary objective is to evaluate the efficacy of iptacopan versus placebo on proteinuria reduction urine protein:creatinine ratio (UPCR) (24 h urine). Key secondary endpoints will assess kidney function measured by eGFR, histological disease total activity score, and fatigue.
UNASSIGNED: This
study aims to demonstrate the clinical benefits of AP inhibition with iptacopan in C3G.