Efficacy and Safety of Vunakizumab and Ivarmacitinib in the Treatment of Active Takayasu's Arteritis

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Vanakizumab
  Vanakizumab 240mg each 4 weeks taken subcutaneously with an additional injection at day 15
• Препарат Ivarmacitinib
  Ivarmacitinib 8mg daily taken orally
• Препарат Prednisone
  Prednisone taken daily according to preset tapering protocol

Первичные конечные точки

• Complete response rate at week 52 [Срок оценки: week 52]

Вторичные конечные точки (6)

• Complete response at week 26 [Срок оценки: week 26]
• Combined response rate of vunakizumab at week 26 and week 52 [Срок оценки: week 26 and week 52]
• Combined response rate of ivarmacitinib at week 26 and week 52 [Срок оценки: week 26 and week 52]
• Time to relapse [Срок оценки: week 52]
• Time to event [Срок оценки: week 52]
• Patient-Reported Outcomes [Срок оценки: week 52]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 20 центров

• Beijing Anzhen Hospital Capital Medical University — Пекин
• Peking Union Medical College Hospital — Пекин
• Xuanwu Hospital Capital Medical University — Пекин
• The First Affiliated Hospital of Sun Yat-sen University — Guanzhou
• Shenzhen People's Hospital — Шэньчжэнь
• People's Hospital of Guangxi Zhuang Autonomous Region — Nanning
• Jiaozuo People's Hospital — Jiaozuo
• The First Affiliated Hospital of Henan University of Science and Technology — Luoyang
• … и ещё 12 центров

Идентификаторы

NCT: NCT07451665 · VIVA-TAK

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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