SAFETY AND EFFICACY OF ISIS 2302 IN STEROID DEPENDENT CROHN'S DISEASE

这是一种六个月，三只手臂，双面罩，随机，安慰剂- ISIS的受控、患者体内重复固定剂量静脉试验 在300名激素依赖型克罗恩病的可评估受试者中有2302名。 ISIS 2302是一种20碱基的硫代寡核苷酸，旨在 特异性地杂交到3‘非翻译区的序列 人细胞间黏附分子-1(ICAM-1)ICAM-1是一种黏附分子 在炎症过程中起重要作用的分子。ISIS 2302 是一种ICAM-1抑制剂。对这种分子的有效抑制将是 预计将具有强大的抗炎潜力，而不是 使用皮质类固醇的伴随副作用。患者将逐渐减少 停用类固醇，然后戴上三个治疗臂之一：高或 低剂量的ISIS 2302，或安慰剂。这将被给予三次，每年 在第一个月和第三个月进行为期4周的训练。疗效将通过以下方式进行评估 1)克罗恩疾病活动性指数(CDAI)的变化；和2) 炎症性肠病问卷(IBDQ)。主端点 将是#年末完全缓解的患者的比例 第14周。受试者将在两个28天的治疗期间进行评估 课程、过渡阶段及随后3个月，以便 观察反应的动力学和持续时间。

This is a six month, three arm, double-masked, randomized, placebo- controlled, repeated fixed dose within patient, intravenous trial of ISIS 2302 in 300 evaluable subjects with steroid-dependent Crohn's disease. ISIS 2302 is a 20 base phosphorothioate oligodeoxynucleotide designed to specifically hybridize to a sequence in the 3' untranslated region of the human Intercellular Adhesion Molecule-1 (ICAM-1). ICAM-1 is an adhesion molecule of fundamental importance to the inflammatory process. ISIS 2302 is a ICAM-1 inhibitor. Effective inhibition of such a molecule would be expected to have potent anti-inflammatory potential without the concomitant side effects of corticosteroid use. Patients will be tapered off their steroids and then put on one of three treatment arms: high or low dose ISIS 2302, or placebo. This will be administered three times a week for 4 weeks in months one and three. Efficacy will be assessed by change in 1) Crohn's Disease Activity Index (CDAI); and 2) the Inflammatory Bowel Disease Questionnaire (IBDQ). The primary endpoint will be the proportion of patients in complete remission at the end of Week 14. Subjects will be evaluated during the two 28 day treatment courses, the interim phase, and for the following 3 months in order to observe the kinetics and duration of response.