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

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-09-08 DOI:10.1007/s12325-025-03299-0

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

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引用次数: 0

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.

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Deucravacitinib是一种口服、选择性、变构性TYK2抑制剂，用于系统性红斑狼疮的两项随机、安慰剂对照、3期试验设计。

背景和目的：Deucravacitinib是一种一流的口服、选择性、变链酪氨酸激酶2抑制剂，在活动性系统性红斑狼疮（SLE）患者的2期PAISLEY SLE试验中，显示出在主要终点和所有关键次要终点的疗效。在这里，我们描述了2项3期试验[POETYK SLE-1 (NCT05617677), POETYK SLE-2 (NCT05620407)]，它们将评估deucravacitinib对活动性SLE患者的有效性和安全性。这些3期试验旨在复制2期试验的成功元素，包括其糖皮质激素减量策略和疾病活动性判断。方法：在这些全球性的3期随机、双盲、安慰剂对照试验中，接受背景标准治疗的18-75岁活动性SLE患者将以3:2的比例随机接受deucravacitinib或安慰剂，进行52周的双盲治疗。在双盲治疗期间，除非出现明显的疾病活动，否则接受糖皮质激素治疗的患者应逐渐减少至阈值剂量水平。在第52周，符合条件的患者可继续进入104周的开放标签延长期，在此期间，所有患者将接受deucravacitinib治疗。计划结局：主要终点SLE Responder Index-4反应和所有次要终点将在第52周进行评估。安全性和耐受性将在整个试验过程中进行评估。在每项试验中，计划随机化包括来自北美、南美、欧洲和亚太地区多个国家的患者。结论：正在进行的POETYK SLE-1和SLE-2试验对于继续评估deucravacitinib作为SLE患者耐受性良好且有效的潜在治疗选择非常重要。试验注册：ClinicalTrials.gov标识符，NCT05617677和NCT05620407。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.