Li Xiaojiao, Li Bing, Yang Deming, Wang Meng, Li Qianqian, Wang Nan, Fang Min, Liu Jingrui, Zhang Hong, Wu Min, Li Cuiyun, Zhu Xiaoxue, Ding Yanhua, Li Shanshan
Phase I Clinical Trial Center, the First Hospital of Jilin University, Changchun, China.
Department of Dermatology and Venereology, the First Hospital of Jilin University, Changchun, China.
JAMA Dermatol. 2025 Mar 1;161(3):247-255. doi: 10.1001/jamadermatol.2024.5059.
Psoriasis is a chronic, immune-mediated skin disease with an unmet need for biologic treatment options.
To assess the safety, pharmacokinetics, and efficacy of QX004N in healthy individuals and patients with moderate to severe plaque psoriasis in China.
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was composed of 2 parts. Part 1 was a first-in-human, single-ascending-dose, phase 1a clinical trial conducted from November 2, 2021, to January 16, 2023. Part 2 was a double-blind, multiple dose-escalation, phase 1b clinical trial conducted from February 15, 2023, to January 5, 2024, at 5 clinical centers in China, involving patients with moderate to severe plaque psoriasis.
In part 1, healthy participants in each cohort were assigned in a 4:1 ratio to receive a single subcutaneous injection of QX004N (ranging from 10 mg to 600 mg) or placebo. In part 2, patients in each cohort were assigned in a 4:1 ratio to receive QX004N or placebo at doses of 150 mg, 300 mg, and 600 mg once every 2 weeks.
For part 1, the primary outcome was the safety of a single dose of QX004N in healthy participants, and the secondary outcome was the pharmacokinetic profile. For part 2, the primary efficacy end point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12; other efficacy end points were considered secondary.
The phase 1a clinical trial (part 1) enrolled 55 healthy participants (mean [SD] age, 35.9 [6.0] years; 30 [54.5%] female), and the phase 1b clinical trial (part 2) enrolled 30 patients with moderate to severe plaque psoriasis. The mean (SD) age of QX004N-treated participants in part 2 was 41.4 (7.5) years, and 19 of 24 QX004N-treated participants (79.2%) were male. The mean (SD) age of the placebo cohort in part 2 was 35.3 (8.4) years, and 5 of 6 placebo-treated participants (83.3%) were male. QX004N exhibited linear pharmacokinetics and was tolerated well in both healthy participants and patients with psoriasis. Most adverse events were mild to moderate in severity, with no drug-related serious adverse events reported. The proportion of patients receiving QX004N who achieved PASI 75 at week 12 and PASI 90 (90% improvement in PASI) at week 16 in the 150-mg, 300-mg, and 600-mg cohorts was 100%, significantly higher than that in the placebo cohorts (33.3%). The maximum proportion of patients achieving Investigator's Global Assessment score of 0 or 1 was 100% in the 3 QX004N cohorts.
In this randomized clinical trial, QX004N was well tolerated and demonstrated superior efficacy compared to placebo in patients with moderate to severe plaque psoriasis.
Chinese Clinical Trial Registry Identifier: CTR20212313 and CTR20223457.
银屑病是一种慢性免疫介导的皮肤病，对生物治疗方案仍有未满足的需求。
评估QX004N在中国健康个体和中度至重度斑块状银屑病患者中的安全性、药代动力学和疗效。
设计、地点和参与者：这项随机临床试验由两部分组成。第1部分是一项首次人体单剂量递增的1a期临床试验，于2021年11月2日至2023年1月16日进行。第2部分是一项双盲、多剂量递增的1b期临床试验，于2023年2月15日至2024年1月5日在中国的5个临床中心进行，涉及中度至重度斑块状银屑病患者。
在第1部分中，每个队列中的健康参与者按4:1的比例分配，接受单次皮下注射QX004N（剂量范围为10mg至600mg）或安慰剂。在第2部分中，每个队列中的患者按4:1的比例分配，每2周接受一次150mg、300mg和600mg剂量的QX004N或安慰剂。
对于第1部分，主要结局是单剂量QX004N在健康参与者中的安全性，次要结局是药代动力学特征。对于第2部分，主要疗效终点是到第12周时银屑病面积和严重程度指数（PASI 75）改善至少75%的患者比例；其他疗效终点视为次要终点。
1a期临床试验（第1部分）纳入了55名健康参与者（平均[标准差]年龄，35.9[6.0]岁；30名[54.5%]为女性），1b期临床试验（第2部分）纳入了30名中度至重度斑块状银屑病患者。第2部分中接受QX004N治疗的参与者的平均（标准差）年龄为41.4（7.5）岁，24名接受QX004N治疗的参与者中有19名（79.2%）为男性。第2部分中安慰剂队列的平均（标准差）年龄为35.3（8.4）岁，接受安慰剂治疗的6名参与者中有5名（83.3%）为男性。QX004N表现出线性药代动力学，在健康参与者和银屑病患者中耐受性良好。大多数不良事件的严重程度为轻度至中度，未报告与药物相关的严重不良事件。在150mg、300mg和600mg队列中，接受QX004N治疗的患者在第12周达到PASI 75和在第16周达到PASI 90（PASI改善90%）的比例为100%，显著高于安慰剂队列（33.3%）。在3个QX004N队列中，达到研究者整体评估评分为0或1的患者的最大比例为100%。
在这项随机临床试验中，QX004N耐受性良好，与安慰剂相比，在中度至重度斑块状银屑病患者中显示出卓越的疗效。
中国临床试验注册标识符：CTR20212313和CTR20223457。
