POS0803 VUNAKIZUMAB IN ACTIVE ANKYLOSING SPONDYLITIS: A RANDOMIZED, DOUBLE-BLIND, ADAPTIVE, SEAMLESS, PHASE 2/3 STUDY

Background:

Vunakizumab (SHR-1314) is a novel humanized monoclonal IgG1/k antibody targeting IL-17A that has previously demonstrated robust efficacy and tolerability in treating plaque psoriasis.

Objectives:

Given the involvement of the IL-17 pathway and overlap in symptoms in psoriasis and ankylosing spondylitis (AS), we conducted a phase 2/3 trial to evaluate the efficacy and safety of vunakizumab in AS.

Methods:

This is a randomized, double-blind, adaptive, seamless, phase 2/3 study (NCT04840485). Eligible patients had active AS (with radiographic evidence fulfilling the modified New York criteria) and inadequate response, contraindications or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs); prior anti-tumor necrosis factor (TNF) therapy was allowed. In the phase 2 part, patients were randomized (2:2:1) to receive vunakizumab 120 mg, 240 mg, or placebo subcutaneously at weeks 0, 2, 4, 8 and 12; at week 16, patients assigned placebo were re-randomized (1:1) to receive vunakizumab 120 mg or 240 mg, and other patients continued on vunakizumab, all Q4W through week 32. A pre-planned interim analysis was performed after all patients completed efficacy and safety assessment at week 16, and vunakizumab 120 mg was determined to be the recommended phase 3 dose per independent data monitoring committee. In the phase 3 part, patients were randomized (2:1) to receive vunakizumab 120 mg or placebo at weeks 0, 2, 4, 8 and 12; from week 16, all patients received vunakizumab 120 mg Q4W through week 32. The primary endpoint was the proportion of patients with ≥20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16.

Results:

During the entire study (phase 2 and 3), a total of 548 patients were randomized, with 294 allocated to vunakizumab 120 mg and 146 to placebo. ASAS20 response rate at week 16 was significantly higher with vunakizumab 120 mg than with placebo (65.6% vs 42.5%, P <0.0001). Similarly, ASAS40 response rate (46.3% vs 24.0%) and other secondary endpoints all favored vunakizumab 120 mg vs placebo at week 16 (Table 1). The ASAS response with vunakizumab 120 mg were sustained through 32 weeks (Figure 1). During the 16-week placebo-controlled period, the overall incidence of adverse events (83.7% vs 81.5%) and infections (37.1% vs 47.3%) were comparable in patients receiving vunakizumab 120 mg and placebo. During the entire 32-week treatment period, 2 (0.4%) cases of cytopenia and 1 (0.2%) case each of cerebrocardiovascular event and inflammatory bowel disease were reported in vunakizumab-treated (any exposure; n=538) patients; no treatment-emergent opportunistic infections, serious infections, malignancies, or deaths occurred.

Conclusion:

Vunakizumab 120 mg significantly improved signs and symptoms of ankylosing spondylitis at week 16 vs placebo, and the efficacy was sustained through 32 weeks. Safety profile of vunakizumab was tolerable. These findings support vunakizumab 120 mg as a new treatment option for active ankylosing spondylitis.

REFERENCES:

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Acknowledgements:

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Disclosure of Interests:

Feng Huang: None declared, Jian Zhu: None declared, Cheng Zhao: None declared, Cundong Mi: None declared, Shengyun Liu: None declared, Rui Wu: None declared, Tianwang Li: None declared, Xinwang Duan: None declared, Lingyun Sun: None declared, Lei Yang: None declared, Xiaohong He: None declared, Wen Liu: None declared, Yasong Li: None declared, Lihui Ma: None declared, Hongwei du: None declared, Ying Liu: None declared, Guoqiang Chen: None declared, Hongwei Zhang: None declared, Tao Wang: None declared, Xiumei Liu: None declared, Xiaofei Shi: None declared, Ju Liu: None declared, Huaxiang Wu: None declared, Hongsheng Sun: None declared, Yuan Xue: None declared, Kexia Chai: None declared, Hongbin Li: None declared, Jiankang Hu: None declared, Zhen Sheng Jiangsu Hengrui Pharmaceuticals, Co., Ltd, Lihua Lin Jiangsu Hengrui Pharmaceuticals, Co., Ltd, Qiuna Du Jiangsu Hengrui Pharmaceuticals, Co., Ltd, Xiaoyan Bai Jiangsu Hengrui Pharmaceuticals, Co., Ltd.