拉托齐奈单抗治疗GRN突变所致额颞叶痴呆的3期随机试验。
摘要
引言：导致额颞叶痴呆（FTD-GRN）的杂合性颗粒体蛋白前体基因突变与颗粒体蛋白前体（PGRN）缺乏相关。拉托齐奈单抗是一种人源单克隆免疫球蛋白G1（IgG1）抗体，旨在提高携带杂合性功能缺失（LOF）GRN突变个体的PGRN水平。…
正文 待译
INTRODUCTION: Heterozygous progranulin gene mutations causing frontotemporal dementia (FTD-GRN) are associated with deficiency in progranulin (PGRN). Latozinemab is a human monoclonal immunoglobulin G1 (IgG1) antibody designed to elevate PGRN levels in people with heterozygous loss-of-function (LOF) GRN mutations. METHODS: A pivotal phase 3 trial, INFRONT-3 (NCT04374136), evaluated the efficacy, safety, and biomarker changes of 60 mg/kg of intravenously administered latozinemab or placebo every 4 weeks for 96 weeks in participants who have or are at risk for FTD due to heterozygous LOF GRN mutations. Those completing the double-blind phase could enter a 96-week open-label safety extension. RESULTS: Although latozinemab administration resulted in sustained elevation of plasma and CSF PGRN concentrations in symptomatic participants with FTD-GRN (primary analysis population), there was no treatment-related slowing of disease progression as measured by clinical or biomarker assessments. No adverse safety signals were identified. DISCUSSION: INFRONT-3 provides the first phase 3 efficacy and safety results for an investigational therapy in FTD-GRN.
English
INTRODUCTION: Heterozygous progranulin gene mutations causing frontotemporal dementia (FTD-GRN) are associated with deficiency in progranulin (PGRN). Latozinemab is a human monoclonal immunoglobulin G1 (IgG1) antibody designed to elevate PGRN levels in people with heterozygous loss-of-function (LOF) GRN mutations.…