Comparison of Deucravacitinib and Adalimumab for the Treatment of Relapsed Takayasu's Arteritis: The TYK-TAK Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Overall response rate at week 24
研究概览
简要总结
This is a 24-week, single-center, randomized, open-label trial conducted by Peking Union Medical College Hospital. The aim of this study is to assess the efficacy and safety of deucravacitinib in adult patients with relapsing TAK in comparison to patients treated with TNF inhibitor (TNFi), the most well-recognized therapeutic choice of non-glucocorticoid immunosuppressive for patients with relapsed or refractory TAK.
详细描述
Background:
The majority of patients with TAK experience relapses, and some patients fail to respond adequately to current medications used for treatment of TAK. There is an urgent unmet need to identify novel therapies to effectively treat TAK. Th-17 and Th-1 cells, and their related cytokines IL-12, IL-23, IL-17, and type I interferon have all been reported to play a role in the pathogenesis of TAK. Tyrosine kinase 2 (TYK2) mediates signaling transduction between these key cytokines and immune cells. Therefore, blocking TYK2 signaling may downregulate potential pathogenic pathways in TAK, and may be a therapeutic alternative. No study has investigated the effectiveness of agents targeting TYK2 in the treatment of TAK so far. In the present study, we aim to investigate whether deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, is effective and safe for patients with relapsed TAK.
Objectives:
To assess the efficacy and safety of deucravacitinib in adult patients with relapsing TAK in comparison to patients treated with TNF inhibitor (TNFi), the most well-recognized therapeutic choice of non-glucocorticoid immunosuppressive for patients with relapsed or refractory TAK.
Overall Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Signed Written Informed Consent
- •Participants fully understand the purpose, nature, method, and possible adverse reactions of the study, willing to consent to the trial and follow study protocol and sign informed consent.
- •Participants must have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines. This ICF must be obtained before performing any protocol related procedures that are not part of normal patient care.
- •Type of Participant and Target Disease Characteristics
- •Adult patients (aged 18 or older) fulfilling the 2022 ACR/EULAR classification criteria for TAK.
- •Persistence of active disease or relapse despite treatment with GCs combined with a conventional synthetic or biologics immunosuppressive agent other than TNFi.
- •Active vasculitis by reader interpretation of FDG-PET at enrollment (by the same reader).
- •Reproductive Status The investigator or designee shall counsel women of childbearing potential (WOCBP) and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy.
- •WOCBP must have a negative highly sensitive specify: urine or serum as required by local regulations pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention.
- •A female is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies:
- •Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year) during the intervention period and for at least 5 half-lives after product administration and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period.
- •WOCBP and male participants who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Medical Conditions
- •Severe disease from TAK for which urgent treatment with interventional procedures or bypass surgery is considered necessary
- •Critical organ involvement of TAK, such as myocardial or coronary artery involvement, or cerebral ischemia
- •Active hepatitis B or C virus infection, active tuberculosis infection
- •Malignancy in the past 5 years (with the exception of fully excised non-melanoma skin cancer or cervical carcinoma in situ)
- •Physical and Laboratory Test Findings
- •Serum liver enzyme tests 3 times higher than the upper limits of normal range
- •Estimated glomerular filtration rate ≤ 30 ml/minute
- •Other Exclusion Criteria
- •Females who are pregnant
- •Ever treated with TNFi (including adalimumab) and discontinued due to inadequate response or intolerance.
- •Any other sound medical, psychiatric, and/or social reason as determined by the investigator
研究组 & 干预措施
Deucravacitinib treatment group
Patients randomly assigned to the deucravacitinib treatment group are required to take the deucravacitinib tablets 6mg orally once daily on an empty stomach or after a meal during D1-D168, and orally take the study drug deucravacitinib with warm water. It is forbidden to drink water from 1 h before administration to 1 h after administration (except for administration of water) and fasting within 1 h after administration. Continuous treatment for 168 days or subject discontinuation criteria were met. The time of dose administration is called "0" hour. Subjects who miss a study medication on one day are not allowed to take a supplement to compensate but should take the next dose.
干预措施: Deucravacitinib (Drug)
Adalimumab treatment group
Participants assigned to the adalimumab treatment group receive adalimumab 40mg by subcutaneous injection every 2 weeks during D1-D168. Adalimumab is administered for 24 weeks unless the discontinuation criteria are met.
干预措施: Adalimumab (Drug)
结局指标
主要结局
Overall response rate at week 24
时间窗: Week 24
* Overall response is defined as the combination of both complete and partial responses. * Complete (treatment) response is defined as the absence or complete resolution of clinical signs and symptoms of active TAK and a patient achieving all of the following: 1. ESR \<20mm/hour; 2. CRP \<10mg/L; 3. No progression of vessel damage in Doppler ultrasonography or CTA, including no new or worsening mural thickness, or stenosis or dilatation; 4. Dose of GC \<15 mg/day prednisone (or equivalent dosage of other GCs). * Partial (treatment) response is defined as the absence or complete resolution of clinical signs and symptoms of active TAK and: 1. ESR \<40mm/hour or decrease by 50% compared to the baseline value; 2. CRP \<20mg/L or decrease by 50% compared to the baseline value; 3. fulfilling the other two criteria of complete response. * The absence or complete resolution of clinical signs and symptoms of active TAK is a pre-required criterion for both complete and partial
次要结局
- Time to clinical remission(from inclusion to the end of the study, 24 weeks in total)
- Disease recurrence after achieving clinical remission(from inclusion to the end of the study, 24 weeks in total)
- Time to disease recurrence(from inclusion to the end of the study, 24 weeks in total)
- Changes in erythrocyte sedimentation rate (ESR)(week 4, 12 and 24)
- Changes in serum C reactive protein (CRP)(week 4, 12 and 24)
- Changes in vascular ultrasonography(from baseline to weeks 12 and 24)
- Changes in PET/CT scans(from the baseline to week 24)
- Change in level of cytokines(week 4, 12 and 24)
研究者
Xinping Tian
Professor of Medicine
Chinese SLE Treatment And Research Group