A Prospective, Open-label, Controlled, Multiple Centers Clinical Study of the Efficacy and Safety for Vunakizumab and Ivarmacitinib in the Treatment of Active Takayasu's Arteritis (TAK): The VIVA-TAK Ttrial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 180
- 试验地点
- 20
- 主要终点
- Complete response rate at week 52
研究概览
简要总结
This is a prospective, open-label, controlled, multiple centers, randonmized clinical trial. It compares the clinical efficacy and safety of vunakizumab ivarmacitinib and glucocorticoids in the treatment of active Takayasu's arteritis.
详细描述
In this study, 180 Takayasu's arteritis patients with active disease will be enrolled. Patients are randomized in to the vunakizumab treatment group, ivarmacitinib treatment group and glucocorticoid treatment group. Patients will follow the same reduction steps for glucocorticoids. The primary endpoint is the percentage of patients who are in complete response at week 52.
The efficacy will be evaluated at week 4, 12, 26, 38 and 52. Safety is also monitored during the study.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •a. Adult patients (aged between 18-70 years) fulfilling the 2022 ACR/EULAR classification criteria for TAK with new-onset or relapsing disease.
- •b. Presence of active disease despite treatment with gluccorticoids combined with a conventional synthetic or biologic immunosuppressive agent other than JAK inhibitors and IL-17 inhibitors, including new-onset patients and relapsed patients.
- •Patient is considered to have active disease by the investigator is the patients meets at least two of the following three criteria: i) one or more clinical manifestations determined by the investigator to be due to active TAK; ii) one or more findings on imaging of progressive disease; or iii) elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Clinical criteria included constitutional symptoms (fever, fatigue, and weight loss), musculoskeletal symptoms, vascular pain, neurological or visual symptoms, abdominal pain or angina, new or worsening limb claudication, loss of pulses, and worsening hypertension. Imaging criteria includes new vascular stenosis or aneurysms detected by ultrasound, computed tomography angiography (CTA), or magnetic resonance angiography.
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 vascular procedures or bypass surgery is considered necessary
- •Critical organ involvement of TAK, such as myocardial or coronary artery involvement, or cerebral ischemia, that is anticipated to need treatment during the study
- •Active hepatitis B or C virus infection
- •Active tuberculosis (Patients with latent tuberculosis infection could be enrolled with preventive therapy for tuberculosis flare)
- •Malignancy in the past 5 years (with the exception of fully excised non-melanoma skin cancer or cervical carcinoma in situ)
- •Poorly controlled diabetes
- •Patients with history of venous thrombosis
- •Upper GI bleeding within 3 months prior to enrollment
- •Uncontrolled heart failure
- •Refractory hypertension
- •Abnormal Laboratory Test Findings k. Serum liver enzyme elevation 3 times higher than the upper limits of normal range l. Severe renal function impairment with estimated glomerular filtration rate ≤ 30 ml/minute/1.73 m2, calculated using the Modification of Diet in Renal Disease equation (doi:10.1056/NEJMoa2102953)
- •Other Exclusion Criteria m. Females who are pregnant or intend to be pregnant during the time frame of the study n. History of treatment with JAKi or IL-17i. o. Any other medical, psychiatric, and/or social reason as determined by the investigator to be a contraindication for study participation
研究组 & 干预措施
Vunakizumab group (Group Vuna I)
Vanakizumab 240mg each 4 weeks subcutaneously (with an additional infection at day 15) for 52 weeks combined with glucocorticoid taken daily according to preset tapering protocol during same period
干预措施: Vanakizumab (Drug)
Vunakizumab group (Group Vuna I)
Vanakizumab 240mg each 4 weeks subcutaneously (with an additional infection at day 15) for 52 weeks combined with glucocorticoid taken daily according to preset tapering protocol during same period
干预措施: Prednisone (Drug)
Ivarmacitinib group (Group Iva I)
Ivarmacitinib 8mg daily taken orally for 52 weeks combined with glucocorticoid taken daily according to preset tapering protocol during same period
干预措施: Ivarmacitinib (Drug)
Ivarmacitinib group (Group Iva I)
Ivarmacitinib 8mg daily taken orally for 52 weeks combined with glucocorticoid taken daily according to preset tapering protocol during same period
干预措施: Prednisone (Drug)
Prednisone group (Group Pred)
Prednisone taken daily according to preset tapering protocol for 52 weeks
干预措施: Prednisone (Drug)
结局指标
主要结局
Complete response rate at week 52
时间窗: week 52
Percentage of patients with complete response at week 52
次要结局
- Complete response at week 26(week 26)
- Combined response rate of vunakizumab at week 26 and week 52(week 26 and week 52)
- Combined response rate of ivarmacitinib at week 26 and week 52(week 26 and week 52)
- Time to relapse(week 52)
- Time to event(week 52)
- Patient-Reported Outcomes(week 52)