背景:细胞膜病包括红细胞膜蛋白遗传变异引起的溶血性疾病,包括遗传性球形细胞增多症和气孔细胞增多症。先天性II型红细胞生成异常性贫血(CDAII)与SEC23B基因相关,并且可以表现出与膜病的表型相似性。目前这些疾病的治疗选择,除了脾切除术,主要是支持。Mitapivat,一种新型丙酮酸激酶(PK)激活剂,已证明在增加PK缺乏患者的血红蛋白水平和减少溶血方面有效,地中海贫血,镰状细胞病和遗传性球形红细胞增多症的小鼠模型。
方法:硫酸米替伐治疗成人红细胞膜病(SATISFY)的安全性和有效性是前瞻性的,多中心,单臂2期试验,纳入约25例诊断为膜病或CDAII的成年患者(≥18岁).在8周剂量递增期间,根据安全性和血红蛋白水平的变化,受试者将接受每天两次50mgmitapivat的初始剂量,并可能在第4周增加至每天两次100mg。耐受米替伐的患者可能有资格在两个连续的24周固定剂量期内继续。这项研究的主要目的是评估mitapivat的安全性,通过治疗紧急不良事件的发生进行评估。次要目标包括评估mitapivat对血红蛋白水平的影响,溶血,红细胞生成,患者报告的结局指标和脾脏大小。SATISFY旨在评估mitapivat在患有红细胞膜病和CDAII的成年患者中的安全性和有效性。目的是在患有这些罕见疾病的患者中建立概念证明。
背景:NCT05935202/CTIS:2023-503271-24-01。研究结果将发表在同行评审的期刊上。
背景:Clinicaltrials.gov,NCT05935202。CTIS:2023-503271-24-01。注册07-7-2023年7月。协议编号:2.1。https://clinicaltrials.gov/study/NCT05935202.
BACKGROUND: Membranopathies encompass haemolytic disorders arising from genetic variants in erythrocyte membrane proteins, including hereditary spherocytosis and stomatocytosis. Congenital dyserythropoietic anaemia type II (CDA II) is associated with the SEC23B gene and can exhibit phenotypic similarities to membranopathies. Current treatment options for these conditions, apart from splenectomy, are primarily supportive. Mitapivat, a novel pyruvate kinase (PK) activator, has demonstrated efficacy in increasing haemoglobin levels and reducing haemolysis in patients with PK deficiency, thalassemia, sickle cell disease and a mouse model of hereditary spherocytosis.
METHODS: Safety and efficacy of mitapivat sulfate in adult patients with erythrocyte membranopathies (SATISFY) is a prospective, multicentre, single-arm phase two trial involving approximately 25 adult patients (≥18 years) diagnosed with a membranopathy or CDA II. During the 8-week dose escalation period, subjects will receive an initial dose of 50 mg mitapivat two times per day and may increase to 100 mg two times per day at week 4 based on the safety and changes in haemoglobin levels. Patients tolerating mitapivat well may be eligible to continue in two consecutive 24-week fixed dose periods.The primary objective of this study is to evaluate the safety of mitapivat, assessed through the occurrence of treatment-emergent adverse events. Secondary objectives include assessing the effects of mitapivat on haemoglobin levels, haemolysis, erythropoiesis, patient-reported outcome measures and spleen size.SATISFY aims to assess the safety and efficacy of mitapivat in adult patients with red blood cell membranopathies and CDA II, with the aim of establishing proof-of-concept in patients living with these rare conditions.
BACKGROUND: NCT05935202/CTIS:2023-503271-24-01. Findings will be published in peer-reviewed journals.
BACKGROUND: Clinicaltrials.gov, NCT05935202. CTIS:2023-503271-24-01. Registered 07-July-2023. Protocol number: 2.1. https://clinicaltrials.gov/study/NCT05935202.