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

这是一项为期6个月的三臂双掩蔽、随机、安慰剂对照、患者体内重复固定剂量的ISIS 2302静脉试验，在300名可评估的类固醇依赖型克罗恩病受试者中进行。ISIS 2302是一个20个碱基的硫代寡核苷酸，专为与人细胞间黏附分子-1(ICAM-1)3‘非翻译区的序列特异性杂交而设计。ICAM-1是一种对炎症过程至关重要的黏附分子。ISIS 2302是一种ICAM-1抑制剂。有效地抑制这种分子有望具有强大的抗炎潜力，而不会伴随使用皮质类固醇的副作用。患者将逐渐减少类固醇，然后接受三种治疗手段之一：高剂量或低剂量ISIS 2302，或安慰剂。这将在第一个月和第三个月每周三次，持续4周。疗效将通过1)克罗恩病活动指数(CDAI)和2)炎症性肠病问卷(IBDQ)的变化来评估。主要终点将是第14周结束时完全缓解的患者的比例。受试者将在两个28天疗程的中间阶段和随后的3个月进行评估，以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.