A Phase 1b clinical trial published in BMC Pharmacology and Toxicology demonstrated that QX002N, an investigational anti–interleukin-17A (IL-17A) monoclonal antibody, exhibited favorable safety and promising efficacy signals in Chinese patients with active ankylosing spondylitis (AS). The randomized, double-blind, placebo-controlled study evaluated multiple ascending doses of the subcutaneous treatment over a 14-week follow-up period.
Safety analysis revealed 85 adverse drug reactions in 20 of the 24 patients (83.3%) who received QX002N, the majority of which were classified as Grade 1–2 in severity. The pharmacokinetic profile showed dose-proportional increases in exposure across the 40 mg to 160 mg range. Efficacy outcomes favored the highest dose group, with patients receiving 160 mg achieving superior response rates compared to lower doses. At Week 8, ASAS20 response reached 87.6%, while ASAS40 response was 50.0% at Week 12. These results exceeded those observed in the 40 mg and 80 mg groups. Pharmacodynamic assessments revealed increased serum IL-17A levels, along with reductions in IL-6, ESR, and hsCRP. Only one patient developed anti-drug antibodies, suggesting low immunogenicity.
An earlier Phase 1 study in 65 healthy Chinese adults confirmed the safety, tolerability, and linear pharmacokinetics of single ascending doses of QX002N (10–320 mg). Most adverse events were mild, with only one Grade 3 event (hypertriglyceridemia) reported. Based on these findings, an 80 mg dose was recommended for subsequent studies.
IL-17A plays a central role in the pathophysiology of ankylosing spondylitis by promoting the activation of neutrophils, macrophages, epithelial cells, and fibroblasts. Accordingly, it represents a validated therapeutic target in AS. QX002N is a novel, high-affinity, humanized IgG1 monoclonal antibody that specifically targets IL-17A. It blocks the interaction of IL-17AA and IL-17AF with the IL-17RA receptor, thereby inhibiting downstream signaling pathways and reducing the secretion of pro-inflammatory cytokines and chemokines such as CXCL-1, IL-6, and IL-8. Preclinical studies have shown that QX002N binds IL-17A with greater affinity than secukinumab and comparable affinity to ixekizumab, suggesting the potential for similar or improved clinical efficacy.
Overall, these results position QX002N as a promising therapeutic candidate for ankylosing spondylitis, with the 160 mg dose demonstrating the most favorable benefit–risk profile. Its linear pharmacokinetics and low immunogenicity further support the continued clinical development of this IL-17A–targeted therapy for inflammatory spinal arthritis.
References
- Wu M, Li Q, Fang M, Zhang H, Ding Y. Safety, pharmacokinetics, preliminary efficacy, pharmacodynamics, and immunogenicity of QX002N, an anti-IL-17A monoclonal antibody, after short-term treatment of active ankylosing spondylitis. BMC Pharmacol Toxicol. 2025 May 19;26(1):107.
- Shen ZW, Wu KQ, Jin TH, Zhao J, Jiang Q, Guo T, Fang M, Chen GL. Pharmacokinetics, Safety, and Immunogenicity of Intravenous and Subcutaneous Single-Dose QX002N Injection in Healthy Subjects: A Randomized, Open, Parallel, Single-Center, Phase I Study. Rheumatol Ther. 2024 Aug;11(4):977-988.