Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing.
SinoMab BioScience, Ltd, Shenzhen, China.
Rheumatology (Oxford). 2022 May 5;61(5):1841-1848. doi: 10.1093/rheumatology/keab699.
SM03, a novel chimaeric mAb specific to B cell-restricted antigen CD22, has been developed to treat RA and other B-cell-related diseases. This 24-week phase II randomized, double-blind, multi-dose, placebo-controlled study aimed to evaluate the efficacy and safety of SM03 in moderately-to-severely active RA patients in China.
One hundred and fifty-six patients on background MTX were randomized in a 1:1:1 ratio to receive a cumulative dose of 3600 mg (high dose, 600 mg × 6 infusions at weeks 0, 2, 4, 12, 14 and 16) or 2400 mg SM03 (low dose, 600 mg × 4 infusions at weeks 0, 2, 12 and 14) or the placebo. The primary outcome was the 24-week ACR 20% improvement criteria (ACR20) response rate. Safety was also assessed.
The 24-week ACR20 response rate was significantly higher with high- (65.3%, P = 0.002) and low-dose SM03 (56.9%, P = 0.024) than with placebo (34.0%), but comparable between the high- and low-dose group. The rate of adverse events was not statistically different among the high-dose group (35.3%), the low-dose group (51.9%) and the placebo group (34.6%). Thirteen (12.6%) patients receiving SM03 reported treatment-emergent infections, including 3.9% patients in the high-dose group. No patients reported severe treatment-emergent infections or malignancies.
In active RA Chinese patients receiving background MTX, SM03 at a cumulative dose of both 2400 mg and 3600 mg is efficacious and well-tolerated throughout the 24 weeks of treatment. Moreover, SM03 has demonstrated a good safety profile.
ClinicalTrials.gov, https://clinicaltrials.gov, NCT04192617.
SM03 是一种新型嵌合单克隆抗体，特异性针对 B 细胞受限抗原 CD22，旨在治疗 RA 和其他 B 细胞相关疾病。这项 24 周的随机、双盲、多剂量、安慰剂对照研究旨在评估 SM03 在我国中重度活跃性 RA 患者中的疗效和安全性。
156 名接受背景 MTX 治疗的患者按 1:1:1 的比例随机分为三组，分别接受累积剂量为 3600mg（高剂量组，600mg×6 次输注，分别在第 0、2、4、12、14 和 16 周）、2400mg SM03（低剂量组，600mg×4 次输注，分别在第 0、2、12 和 14 周）或安慰剂。主要终点是第 24 周 ACR20%改善标准（ACR20）应答率。同时评估安全性。
高剂量组（65.3%，P=0.002）和低剂量组（56.9%，P=0.024）的 24 周 ACR20 应答率明显高于安慰剂组（34.0%），但高剂量组与低剂量组之间无统计学差异。高剂量组（35.3%）、低剂量组（51.9%）和安慰剂组（34.6%）的不良事件发生率无统计学差异。接受 SM03 治疗的 13 名（12.6%）患者发生治疗后感染，其中高剂量组为 3.9%。无患者报告严重治疗后感染或恶性肿瘤。
在接受背景 MTX 治疗的活动期 RA 中国患者中，累积剂量为 2400mg 和 3600mg 的 SM03 治疗 24 周是有效且耐受良好的。此外，SM03 具有良好的安全性。
ClinicalTrials.gov，网址：https://clinicaltrials.gov，NCT04192617。
