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

这是在300名患有类固醇依赖性克罗恩病的可评价受试者中进行的ISIS 2302的六个月、三组、双盲、随机、安慰剂对照、患者内重复固定剂量、静脉内试验。 ISIS 2302是一种20个碱基的硫代磷酸寡脱氧核苷酸，设计用于与人细胞间粘附分子-1（ICAM-1）3'非翻译区中的序列特异性杂交。ICAM-1是一种对炎症过程至关重要的粘附分子。 ISIS 2302是ICAM-1抑制剂。 预期这种分子的有效抑制具有有效的抗炎潜力，而没有皮质类固醇使用的伴随副作用。患者将逐渐减少他们的类固醇，然后接受三个治疗组之一：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给药三次，持续4周。将通过1）克罗恩病活动指数（CDAI）和2）炎症性肠病问卷（IBDQ）的变化评估疗效。主要终点为第14周结束时完全缓解的患者比例。 将在两个28天疗程、中期和随后3个月内对受试者进行评价，以观察动力学和缓解持续时间。

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.