两项随机、安慰剂对照的3期试验设计：口服选择性变构酪氨酸激酶2（TYK2）抑制剂德卡伐替尼治疗系统性红斑狼疮

Design of Two Randomized, Placebo-Controlled, Phase 3 Trials of Deucravacitinib, an Oral, Selective, Allosteric TYK2 Inhibitor, in Systemic Lupus Erythematosus.

作者信息

Arriens Cristina, Morand Eric F, Askanase Anca D, Furie Richard, van Vollenhoven Ronald F, Tanaka Yoshiya, Connors Kevin, Davey Monica, Young Kimberly, Franchin Giovanni, Meier Richard, Shah Vaishali, de Oliveria Carolina Leite, Hobar Coburn

机构信息

Department of Arthritis and Clinical Immunology, Rheumatology, Oklahoma Medical Research Foundation and Department of Medicine, University of Oklahoma Health Sciences Center, 825 NE 13th St, Oklahoma City, OK, 73104, USA.

Centre for Inflammatory Diseases, Monash University, Clayton, VIC, 3168, Australia.

出版信息

Adv Ther. 2025 Sep 8. doi: 10.1007/s12325-025-03299-0.

DOI:10.1007/s12325-025-03299-0

PMID:40920289

Abstract

BACKGROUND AND OBJECTIVES

Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, demonstrated efficacy across the primary endpoint and all key secondary endpoints in the phase 2 PAISLEY SLE trial in patients with active systemic lupus erythematosus (SLE). Here, we describe 2 phase 3 trials [POETYK SLE-1 (NCT05617677), POETYK SLE-2 (NCT05620407)] which will assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and disease activity adjudication.

METHODS

In these global, phase 3, randomized, double-blind, placebo-controlled trials, patients aged 18-75 years with active SLE receiving background standard-of-care treatment will be randomized 3:2 to receive deucravacitinib or placebo for 52 weeks of double-blind treatment. Patients receiving glucocorticoids will be instructed to taper, unless significant disease activity is present, to a threshold dose level during the double-blind treatment period. At week 52, eligible patients may continue to an optional 104-week open-label extension phase, in which all patients will receive deucravacitinib.

PLANNED OUTCOMES

The primary endpoint of SLE Responder Index-4 response and all secondary endpoints will be assessed at week 52. Safety and tolerability will be assessed throughout the trials. In each trial, planned randomization includes patients in multiple countries across North and South America, Europe, and the Asia-Pacific region.

CONCLUSIONS

The POETYK SLE-1 and SLE-2 trials in progress are important to the continued evaluation of deucravacitinib as a potential well-tolerated and effective therapy option for patients with SLE.

TRIAL REGISTRATION

ClinicalTrials.gov identifiers, NCT05617677 and NCT05620407.

摘要

背景与目的

德卡伐替尼是首个口服、选择性、变构酪氨酸激酶2抑制剂，在2期PAISLEY系统性红斑狼疮（SLE）试验中，在主要终点和所有关键次要终点方面均显示出疗效。在此，我们描述两项3期试验[POETYK SLE-1（NCT05617677）、POETYK SLE-2（NCT05620407）]，这两项试验将评估德卡伐替尼在活动性SLE患者中的疗效和安全性。这些3期试验旨在重复2期试验的成功要素，包括其糖皮质激素减量策略和疾病活动判定。

方法

在这些全球性、3期、随机、双盲、安慰剂对照试验中，年龄在18至75岁、接受背景标准治疗的活动性SLE患者将按3:2随机分组，接受德卡伐替尼或安慰剂进行52周的双盲治疗。接受糖皮质激素治疗的患者将被指导逐渐减量，除非存在显著疾病活动，在双盲治疗期间减至阈值剂量水平。在第52周时，符合条件的患者可继续进入为期104周的开放标签延长期，在此期间所有患者将接受德卡伐替尼治疗。