医学
血小板
不利影响
安慰剂
内科学
胃肠病学
自身抗体
临床终点
免疫系统
血小板活化
免疫学
抗体
临床试验
病理
替代医学
作者
David J. Kuter,James B. Bussel,Waleed Ghanima,Nichola Cooper,Terry Gernsheimer,Michele P. Lambert,Howard A. Liebman,Michael D. Tarantino,Michelle Lee,Haoran Guo,Ahmed Daak
标识
DOI:10.1177/20406207231205431
摘要
Background: Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 10 9 /L and increase from baseline ⩾20 × 10 9 /L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels. Objectives: Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP. Design: Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study. Methods and analysis: The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 10 9 /L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy. Ethics: Ethical guidelines and informed consent are followed. Discussion: The LUNA 3 trial will further investigate rilzabrutinib’s safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response. Trail Registration: ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766 ; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60 .
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