STARS - Prospective, bayesian, randomized, controlled, open-label, parallel-group, phase II interventional study evaluating efficacy and safety of secukinumab versus standard of care in active severe Takayasu patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 15
- 主要终点
- Disease remission (defined by NIH score ≤ 1) at 6 months and with prednisone discontinuation Disease activity is measured according to National Institutes of Health (NIH) criteria (Kerr 1994) and comprises four variables, each scoring one point as below (scale range 0-4 points). A score equal or superior to 2 is considered as active disease.
研究概览
简要总结
To evaluate disease remission (defined by a NIH score ≤ 1) at 6 months in severe TAK patients and with discontinuation of prednisone
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 0-17 Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patients ≥15 years and Signed informed consent
- •Affiliation with the French national social security system. Patients with AME are eligible
- •Adequate and effective contraceptive measures based on CTFG update of recommendations version 1.1 dated 21-Sep-2020
- •For women of childbearing age, a negative serum or urinary pregnancy test
- •Diagnosis of TAK based on the 2022 American College of Rheumatology/EULAR and/or Ishikawa criteria modified by Sharma
- •Active TAK defined by a National Institutes of Health [NIH] score >1 in the past 2 months
- •Severe TAK, defined as either refractory/relapsing disease or by the presence of severe arterial involvement at baseline
- •Patients must be eligible to receive prednisone (or equivalent) 10-50 mg daily at baseline. Oral corticosteroids must be at a stable dose for at least 2 weeks prior to the first administration of study drug at Day
- •Absence of chronic active infections. Patients with a positive TB test may participate in the study if further work up (according to local practice/guidelines) conclusively establishes that the patient has no evidence of active tuberculosis
排除标准
- •Inability to comply with study guidelines or provide informed consent
- •Blood count abnormality: a. Platelet count < 50 x 10.3/mm3 b. Neutropenia < 1000/mm3 c. Haemoglobin < 8 g/dl c. Hémoglobine < 8 g/dl
- •Pregnancy or breastfeeding
- •History of severe immunosuppression, positive serology for HIV or positive HBsAg
- •Infection requiring treatment with intravenous antibiotics within 2 weeks prior to the inclusion & randomization visit
- •Contraindication or hypersensitivity to Secukinumab, TNF inhibitors or tocilizumab, corticosteroids, TB prophylactic treatment or to any of their excipients
- •Have received live vaccines within 3 months prior to inclusion
- •History of malignancy in the last 5 years (except adequately treated basal or squamous cell carcinoma of the skin)
- •Severe renal impairment (creatinine clearance <30mL/min/1.73m2)
- •History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests such as Aspartate Aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or serum bilirubin. The investigator should be guided by the following criteria: a. SGOT (AST) and SGPT (ALT) may not exceed 3 × the upper limit of normal (ULN). A single parameter elevated up to and including 3 × ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error. b. Alkaline phosphatase may not exceed 4 × ULN. An elevation up to and including 4 × ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error. c. Total bilirubin may not exceed 4 × ULN. If the total bilirubin concentration is increased above 4 × ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin
结局指标
主要结局
Disease remission (defined by NIH score ≤ 1) at 6 months and with prednisone discontinuation Disease activity is measured according to National Institutes of Health (NIH) criteria (Kerr 1994) and comprises four variables, each scoring one point as below (scale range 0-4 points). A score equal or superior to 2 is considered as active disease.
Disease remission (defined by NIH score ≤ 1) at 6 months and with prednisone discontinuation Disease activity is measured according to National Institutes of Health (NIH) criteria (Kerr 1994) and comprises four variables, each scoring one point as below (scale range 0-4 points). A score equal or superior to 2 is considered as active disease.
• Criterion 1 scores if at least one of the following systemic characteristics, without any other cause identified: o Constitutional symptoms such as low-grade fever, weight loss and fatigue; o Extra-vascular manifestations (e.g., polyarthralgia / arthritis, erythema nodosum, episcleritis, etc).
• Criterion 1 scores if at least one of the following systemic characteristics, without any other cause identified: o Constitutional symptoms such as low-grade fever, weight loss and fatigue; o Extra-vascular manifestations (e.g., polyarthralgia / arthritis, erythema nodosum, episcleritis, etc).
• Criterion 2 scores if at least one of the following clinical signs have appeared since the previous visit: o New carotidodynia, vascular claudication or pain along an arterial pathway o New transient ischemic attack (TIA), stroke, acute coronary syndrome or instable angina o New pulse loss o New vascular bruit o New anisotension
• Criterion 2 scores if at least one of the following clinical signs have appeared since the previous visit: o New carotidodynia, vascular claudication or pain along an arterial pathway o New transient ischemic attack (TIA), stroke, acute coronary syndrome or instable angina o New pulse loss o New vascular bruit o New anisotension
• Criterion 3 scores if at least one of the following biological inflammatory markers are elevated in the absence of any other reason: o Erythrocyte sedimentation rate at 1 hour > 30 mm/h ; o C-reactive protein > 10 mg/L ; o Fibrinogen > 4 g/L.
• Criterion 3 scores if at least one of the following biological inflammatory markers are elevated in the absence of any other reason: o Erythrocyte sedimentation rate at 1 hour > 30 mm/h ; o C-reactive protein > 10 mg/L ; o Fibrinogen > 4 g/L.
• Criterion 4 scores if at least one of the following radiological signs appears in a otherwise unaffected arterial territory: o New arterial wall thickening with wall contrast enhancement in vascular imaging Appearance of new vascular lesions (e.g., New arterial wall thickening stenosis, aneurysms) in Doppler, MRA, computed tomography angiography (CTA) or new hypermetabolism in 18-Fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET).
• Criterion 4 scores if at least one of the following radiological signs appears in a otherwise unaffected arterial territory: o New arterial wall thickening with wall contrast enhancement in vascular imaging Appearance of new vascular lesions (e.g., New arterial wall thickening stenosis, aneurysms) in Doppler, MRA, computed tomography angiography (CTA) or new hypermetabolism in 18-Fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET).
次要结局
- Cumulative incidence of relapse over the 12 months after initiation of experimental treatment
- Cumulative incidence of treatment failure over the 12 months after initiation of experimental therapy
- Cumulative prednisone dose over the 12 months after initiation of experimental treatment
- Glucocorticoid-free disease remission will be assessed at 3, 6, and 12 months using the primary composite endpoint
- Cumulative incidence of AE and SAE over the 12 months after initiation of investigational therapy
- Change in the Physical Component Summary (PCS) of the SF36 between the start of experimental treatment,6 and 12 months after
- Change in vascular lesions at 3, 6, and 12 months after the start of experimental treatment, measured by angio CT and/or magnetic resonance imaging angiography and/or Doppler
- Change in vascular hypermetabolism at 6 and 12 months after the start of experimental treatment, measured by 18-FDG-PET
- - Cumulative incidence of revascularization procedures (endovascular or surgical) required because of disease at 6 and 12 months after initiation of experimental therapy.
研究者
David SAADOUN
Scientific
Assistance Publique Hopitaux De Paris