University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
Faculty of Medicine Graduate School of Medicine, Department of Respiratory Medicine and Clinical Immunology, Osaka University, Suita, Osaka, Japan.
RMD Open. 2024 Sep 17;10(3):e004701. doi: 10.1136/rmdopen-2024-004701.
To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response and efficacy of E6742 in a phase I/II study in patients with systemic lupus erythematosus (SLE).
Two sequential cohorts of patients with SLE were enrolled and randomised to 12 weeks of two times per day treatment with E6742 (100 or 200 mg; n=8 or 9) or placebo (n=9). The primary endpoint was safety, the secondary endpoints were PK and interferon gene signature (IGS), and the exploratory endpoints were efficacy and biomarker.
The proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% (3/8 patients) for 100 mg; 77.8% (7/9 patients) for 200 mg) and 66.7% (6/9 patients) in the placebo group. No Common Terminology Criteria for Adverse Events≥Grade 3 TEAEs occurred. PK parameters were similar to these in previous phase I studies in healthy adults. The IGS and levels of proinflammatory cytokines after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. The response rate of the British Isles Lupus Assessment Group-based Composite Lupus Assessment at week 12 was 37.5% (3/8 patients) for E6742 100 mg, 57.1% (4/7 patients) for E6742 200 mg and 33.3% (3/9 patients) for placebo group.
E6742 had a favourable safety profile and was well tolerated, with suppression of IGS responses and preliminary efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials.
NCT05278663.
评估 E6742 在系统性红斑狼疮（SLE）患者中的安全性、耐受性、药代动力学（PK）、生物标志物反应和疗效。
先后纳入两批 SLE 患者，并将其随机分为两组，分别接受 E6742（100 或 200mg，每日两次）或安慰剂治疗 12 周（每组 8 或 9 例）。主要终点为安全性，次要终点为 PK 和干扰素基因特征（IGS），探索性终点为疗效和生物标志物。
E6742 组的任何治疗相关不良事件（TEAE）发生率为 58.8%（100mg 组为 37.5%[3/8 例]；200mg 组为 77.8%[7/9 例]），安慰剂组为 66.7%（6/9 例）。未发生任何不良事件≥3 级的常见术语标准（CTCAE）。PK 参数与之前在健康成年人中的 I 期研究相似。E6742 治疗可立即降低 Toll 样受体 7/8 激动剂体外刺激后的 IGS 和促炎细胞因子水平。E6742 100mg 组在第 12 周的英国狼疮评估组综合狼疮评估的缓解率为 37.5%（3/8 例），E6742 200mg 组为 57.1%（4/7 例），安慰剂组为 33.3%（3/9 例）。
E6742 具有良好的安全性和耐受性，可抑制 SLE 患者的 IGS 反应和初步疗效信号。这些结果为 E6742 治疗 SLE 提供了首个临床证据，并支持更大规模、更长时间的临床试验。
NCT05278663。
