Evaluation of efficacy and safety of rituximab in patients with progressive interstitial lung disease (ILD) with inflammatory component (EvER-ILD2): A multicentre double-blind placebo-controlled randomized trial

IF 2.2 4区医学 Q3 RESPIRATORY SYSTEM

Respiratory Medicine and Research Pub Date : 2024-11-28 DOI:10.1016/j.resmer.2024.101144

Marion Ferreira , Theodora Bejan-Angoulvant , Sylvain Marchand-Adam , Elodie Mousset , Elody Mureau , Stéphane Jouneau , Hilario Nunes , David Montani , Cécile Chenivesse , Jacques Cadranel , Philippe Bonniaud , Bruno Crestani , Vincent Cottin , Agnès Caille , OrphaLung.

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Abstract

Introduction

Progressive interstitial lung diseases (ILDs) are rare but severe diseases, with high mortality and morbidity, with no effective pharmacological treatment allowing for long-term remission, and therefore no clear therapeutic recommendations. Several ILDs present inflammatory components (ILDic), which may justify the use of anti-inflammatory and immunosuppressive drugs, as first-step therapy. Except for systemic sclerosis (SSc)–ILD and sarcoidosis, the evidence in favor of this approach is very weak. The EvER-ILD2 study is the first one to prospectively evaluate the efficacy and safety of rituximab (RTX) versus placebo in a broad range of progressive ILD outside sarcoidosis and connective tissue diseases. A pharmacokinetic-pharmacodynamic analysis based on RTX serum concentrations will allow identification of potential factors associated with therapeutic response and/or adverse effects.

Methods

EvER-ILD2 study is a French multicentre, prospective, randomized, double blind, placebo-controlled, superiority trial. Patients with progressive ILDic will be randomized into 2 groups of treatment: one course of RTX (RTX group) and one course of placebo (Placebo group). The primary outcome is the change in Forced Vital Capacity (FVC, mL) from baseline to 6 months. Several clinical, biological, and quality of life secondary outcomes will be measured at 3 and 6 months. A sample size of 126 patients (63 patients per group) would allow to show a 100 mL difference between groups in the change of FVC from baseline to 6 months, based on a common standard deviation for FVC change of 200 mL with a power of 80% and a two-sided alpha of 5%.

Ethics and dissemination

The protocol was approved by the French Research Ethics Committee (CPP Ile de France VI) on September 27, 2022, and by the French competent authority on October 02, 2022. This article refers to protocol V1, dated September 2022. An independent data safety monitoring board will review safety data for the duration of the trial. Results will be disseminated via peer reviewed publication and presentation at international conferences.

Trial registration number

NCT05596786 (clinicaltrials.gov), EU-CT number 2022–500,375–31–00 (European Medicines agency).

查看原文本刊更多论文

利妥昔单抗治疗伴有炎症成分（EvER-ILD2）的进行性间质性肺病（ILD）患者的疗效和安全性评价：一项多中心双盲安慰剂对照随机试验

进行性间质性肺疾病（ILDs）是罕见但严重的疾病，死亡率和发病率高，没有有效的药物治疗允许长期缓解，因此没有明确的治疗建议。一些ILDs存在炎症成分（ILDic），这可能证明使用抗炎和免疫抑制药物作为第一步治疗是合理的。除了系统性硬化症(SSc)-ILD和结节病外，支持这种方法的证据非常薄弱。all - ild2研究是第一个前瞻性评估利妥昔单抗（RTX）与安慰剂在广泛的进行性肺间质瘤病和结缔组织疾病外的疗效和安全性的研究。基于RTX血清浓度的药代动力学-药效学分析将允许识别与治疗反应和/或不良反应相关的潜在因素。方法：EvER-ILD2研究是法国一项多中心、前瞻性、随机、双盲、安慰剂对照的优势试验。进行性ILDic患者将随机分为两组治疗：一个疗程的RTX （RTX组）和一个疗程的安慰剂（安慰剂组）。主要结局是强迫肺活量（FVC, mL）从基线到6个月的变化。在第3个月和第6个月时测量一些临床、生物学和生活质量的次要结果。126例患者（每组63例患者）的样本量将允许显示组间FVC变化从基线到6个月的100 mL差异，基于FVC变化的共同标准偏差为200 mL，功率为80%，双侧alpha为5%。伦理和传播：该方案于2022年9月27日由法国研究伦理委员会（CPP Ile de France VI）批准，并于2022年10月2日由法国主管当局批准。本文指的是日期为2022年9月的V1协议。一个独立的数据安全监测委员会将审查试验期间的安全数据。研究结果将通过同行评议的出版物和在国际会议上发表来传播。试验注册号：NCT05596786 (clinicaltrials.gov)， EU-CT号：2022-500,375-31-00（欧洲药品管理局）。

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