设计一项用于治疗红细胞膜病变成年患者的米他培坦单臂 2 期临床试验（SATISFY）：罕见性贫血介入治疗试验框架——初步研究方案。
Designing a single-arm phase 2 clinical trial of mitapivat for adult patients with erythrocyte membranopathies (SATISFY): a framework for interventional trials in rare anaemias - pilot study protocol.
机构信息
Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
出版信息
BMJ Open. 2024 Jul 30;14(7):e083691. doi: 10.1136/bmjopen-2023-083691.
INTRODUCTION
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 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 AND ANALYSES
fey and effcacy of mitapivat ulate in adult patients with erthrocyte 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.
ETHICS AND DISSEMINATION
NCT05935202/CTIS:2023-503271-24-01. Findings will be published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
Clinicaltrials.gov, NCT05935202. CTIS:2023-503271-24-01. Registered 07-July-2023. Protocol number: 2.1. https://clinicaltrials.gov/study/NCT05935202.
简介
膜病包括由红细胞膜蛋白的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口形细胞增多症。先天性红细胞生成性卟啉病 II 型（CDA II）与 基因相关，其表型可与膜病相似。除脾切除术外，这些疾病的当前治疗选择主要是支持性的。新型丙酮酸激酶（PK）激活剂米替膦酸已证明在 PK 缺乏症、地中海贫血、镰状细胞病和遗传性球形细胞增多症的小鼠模型中，可增加血红蛋白水平和减少溶血。
方法和分析
红细胞膜病（SATISFY）中米替膦酸的疗效和安全性是一项前瞻性、多中心、单臂 II 期试验，涉及约 25 名成年患者（≥18 岁），诊断为膜病或 CDA II。在 8 周的剂量递增期，患者将接受初始剂量为 50mg 米替膦酸，每日两次，并可根据安全性和血红蛋白水平的变化在第 4 周增加至每日两次 100mg。耐受米替膦酸的患者可能有资格继续进行两个连续的 24 周固定剂量期。本研究的主要目的是评估米替膦酸的安全性，通过治疗出现的不良事件来评估。次要目标包括评估米替膦酸对血红蛋白水平、溶血、红细胞生成、患者报告的结果测量和脾脏大小的影响。SATISFY 旨在评估米替膦酸在患有红细胞膜病和 CDA II 的成年患者中的安全性和疗效，目的是在患有这些罕见疾病的患者中建立概念验证。
伦理和传播
NCT05935202/CTIS：2023-503271-24-01。研究结果将发表在同行评议的期刊上。
试验注册号码
Clinicaltrials.gov，NCT05935202。CTIS：2023-503271-24-01。注册日期：2023 年 7 月 7 日。方案编号：2.1。https://clinicaltrials.gov/study/NCT05935202。
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